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Sample records for blood coagulation factor inhibitors

  1. Blood coagulation factors as inflammatory mediators

    NARCIS (Netherlands)

    Schoenmakers, Saskia H. H. F.; Reitsma, Pieter H.; Spek, C. Arnold

    2005-01-01

    After the first observations about blood coagulation by Hippocrates, it took until the early 1900s before the classic theory of blood coagulation was presented. As more and more other coagulation factors were discovered, the four-factor coagulation scheme became more complex, but better understood,

  2. Bioassay-directed fractionation of a blood coagulation factor Xa inhibitor, betulinic acid from Lycopus lucidus

    Directory of Open Access Journals (Sweden)

    Tan Yin-Feng

    2018-03-01

    Full Text Available Thrombosis is a major cause of morbidity and mortality worldwide and plays a pivotal role in the pathogenesis of several cardiovascular disorders, including acute coronary syndrome, unstable angina, myocardial infarction, sudden cardiac death, peripheral arterial occlusion, ischemic stroke, deep-vein thrombosis, and pulmonary embolism. Anticoagulants, antiplatelet agents, and fibrinolytics can reduce the risks of these clinical events. Especially, the blood coagulation factor Xa (FXa inhibitor is a proven anticoagulant. Promoting blood circulation, using traditional Chinese medicine (TCM, for the treatment of these diseases has been safely used for thousands of years in clinical practice. Therefore, highly safe and effective anticoagulant ingredients, including FXa inhibitors, could be found in TCM for activating the blood circulation. One FXa inhibitor, a pentacyclic triterpene (compound 1, betulinic acid characterized by IR, MS and NMR analyses, was isolated from the ethyl acetate fraction of Lycopus lucidus by bioassay-directed fractionation. Compound 1 exhibited an inhibitory effect on FXa with IC50 25.05 μmol/L and reduced the thrombus weight in an animal model at 25-100 mg/kg. These results indicate that betulinic acid could be the potential for anticoagulant therapy.

  3. Postprandial triglycerides and blood coagulation.

    Science.gov (United States)

    Silveira, A

    2001-01-01

    Most of our lifetime we spend in the postprandial state. Postprandial triglyceridemia may represent a procoagulant state involving disturbances of both blood coagulation and fibrinolysis, in particular due to elevation of the plasma levels of activated factor VII (VIIa) and plasminogen activator inhibitor (PAI-1). Therefore, disturbances of the hemostatic system might, at least partly, account for by the link between hypertriglyceridemia and coronary heart disease (CHD). Factor VIIa is the first enzyme of the blood coagulation system and serves a priming function for triggering of the clotting cascade. The coagulant activity of factor VII (VIIc, total activity of factor VII in plasma) was identified as an independent predictor of myocardial infarction in initially healthy middle-aged men, and particularly of fatal coronary events, and both serum cholesterol and triglyceride concentrations correlated positively with the VIIc level. Addition of fat to diet has been consistently shown to cause a rapid conversion of the factor VII zymogen into its active form (VIIa) whereas the concentration of total protein is unaffected. Postprandial activation of factor VII is dependent on lipolytic activity and it is mainly supported by large triglyceride-rich lipoprotein of the VLDL class. Studies in vivo with specific coagulation factor-deficient patients indicate that factor IX is essential for the postprandial activation of factor VII. The basal generation of thrombin seems to be unaffected by increased plasma levels of VIIa. However, since VIIa-tissue factor complex is responsible for the initiation of the coagulation cascade, increased generation of VIIa in the postprandial state would increase the potential for thrombin production in the event of plaque rupture. Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of the plasminogen activators in the circulation and thereby the principal inhibitor of the fibrinolytic system. Postprandial

  4. Blood coagulation factor VIII

    Indian Academy of Sciences (India)

    Factor VIII (FVIII) functions as a co-factor in the blood coagulation cascade for the proteolytic activation of factor X by factor IXa. Deficiency of FVIII causes hemophilia A, the most commonly inherited bleeding disorder. This review highlights current knowledge on selected aspects of FVIII in which both the scientist and the ...

  5. Recombinant nematode anticoagulant protein c2, an inhibitor of tissue factor/factor VIIa, attenuates coagulation and the interleukin-10 response in human endotoxemia

    NARCIS (Netherlands)

    de Pont, A. C. J. M.; Moons, A. H. M.; de Jonge, E.; Meijers, J. C. M.; Vlasuk, G. P.; Rote, W. E.; Büller, H. R.; van der Poll, T.; Levi, M. [=Marcel M.

    2004-01-01

    The tissue factor-factor (F)VIIa complex (TF/FVIIa) is responsible for the initiation of blood coagulation under both physiological and pathological conditions. Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of TF/FVIIa. mechanistically distinct from tissue factor

  6. Engineering the substrate and inhibitor specificities of human coagulation Factor VIIa

    DEFF Research Database (Denmark)

    Larsen, Katrine S; Østergaard, Henrik; Bjelke, Jais R

    2007-01-01

    The remarkably high specificity of the coagulation proteases towards macromolecular substrates is provided by numerous interactions involving the catalytic groove and remote exosites. For FVIIa [activated FVII (Factor VII)], the principal initiator of coagulation via the extrinsic pathway, several...... for FVIIa by marked changes in primary substrate specificity and decreased rates of antithrombin III inhibition. Interestingly, these changes do not necessarily coincide with an altered ability to activate Factor X, demonstrating that inhibitor and macromolecular substrate selectivity may be engineered...

  7. Expression of human blood coagulation factor XI: characterization of the defect in factor XI type III deficiency

    NARCIS (Netherlands)

    Meijers, J. C.; Davie, E. W.; Chung, D. W.

    1992-01-01

    Human factor XI (FXI) is a blood coagulation factor participating in the early phase of the intrinsic pathway of blood coagulation. It circulates in blood as a glycoprotein composed of two identical chains held together by a single disulfide bond between the fourth apple domains. FXI has been

  8. Discovery of a Parenteral Small Molecule Coagulation Factor XIa Inhibitor Clinical Candidate (BMS-962212).

    Science.gov (United States)

    Pinto, Donald J P; Orwat, Michael J; Smith, Leon M; Quan, Mimi L; Lam, Patrick Y S; Rossi, Karen A; Apedo, Atsu; Bozarth, Jeffrey M; Wu, Yiming; Zheng, Joanna J; Xin, Baomin; Toussaint, Nathalie; Stetsko, Paul; Gudmundsson, Olafur; Maxwell, Brad; Crain, Earl J; Wong, Pancras C; Lou, Zhen; Harper, Timothy W; Chacko, Silvi A; Myers, Joseph E; Sheriff, Steven; Zhang, Huiping; Hou, Xiaoping; Mathur, Arvind; Seiffert, Dietmar A; Wexler, Ruth R; Luettgen, Joseph M; Ewing, William R

    2017-12-14

    Factor XIa (FXIa) is a blood coagulation enzyme that is involved in the amplification of thrombin generation. Mounting evidence suggests that direct inhibition of FXIa can block pathologic thrombus formation while preserving normal hemostasis. Preclinical studies using a variety of approaches to reduce FXIa activity, including direct inhibitors of FXIa, have demonstrated good antithrombotic efficacy without increasing bleeding. On the basis of this potential, we targeted our efforts at identifying potent inhibitors of FXIa with a focus on discovering an acute antithrombotic agent for use in a hospital setting. Herein we describe the discovery of a potent FXIa clinical candidate, 55 (FXIa K i = 0.7 nM), with excellent preclinical efficacy in thrombosis models and aqueous solubility suitable for intravenous administration. BMS-962212 is a reversible, direct, and highly selective small molecule inhibitor of FXIa.

  9. Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Skouby, S O.; Andersen, L F

    2002-01-01

    BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor...... pathway inhibitor (TFPI) may be deleterious. METHODS: We measured factor VII clotting activity, activated factor VII, and concentrations of factor VII and TFPI during 12 months in healthy post-menopausal women randomized to: (i). cyclic oral estrogen/progestin (n = 25); (ii). long-cycle oral estrogen......: No variations were observed in the reference group. There was a substantial decrease in TFPI concentrations in the HRT groups irrespective of the type of progestin. In women receiving long-cycle treatment, all factor VII measures increased during the unopposed estrogen periods, and the increase was reversed...

  10. A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

    DEFF Research Database (Denmark)

    Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik

    2007-01-01

    Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD......) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation...... in the presence of TF or an active-site inhibitor. Based on MD simulations, a key switch of the TF-induced structural changes is identified as the interacting pair Leu305{163} and Phe374{225} in FVIIa, whose mutual conformations are guided by the presence of TF and observed to be closely linked to the structural...

  11. Hemophilia as a defect of the tissue factor pathway of blood coagulation: Effect of factors VIII and IX on factor X activation in a continuous-flow reactor

    International Nuclear Information System (INIS)

    Repke, D.; Gemmell, C.H.; Guha, A.; Turitto, V.T.; Nemerson, Y.; Broze, G.J. Jr.

    1990-01-01

    The effect of factors VIII and IX on the ability of the tissue factor-factor VIIa complex to activate factor X was studied in a continuous-flow tubular enzyme reactor. Tissue factor immobilized in a phospholipid bilayer on the inner surface of the tube was exposed to a perfusate containing factors VIIa, VIII, IX, and X flowing at a wall shear rate of 57, 300, or 1130 sec -1 . The addition of factors VIII and IX at their respective plasma concentrations resulted in a further 2 endash-to 3 endash fold increase. The direct activation of factor X by tissue factor-factor VIIa could be virtually eliminated by the lipoprotein-associated coagulation inhibitor. These results suggest that the tissue factor pathway, mediated through factors VIII and IX, produces significant levels of factor Xa even in the presence of an inhibitor of the tissue factor-factor VIIa complex; moreover, the activation is dependent on local shear conditions. These findings are consistent both with a model of blood coagulation in which initiation of the system results from tissue factor and with the bleeding observed in hemophilia

  12. Plasma concentrations of blood coagulation factor VII measured by immunochemical and amidolytic methods

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Gram, J; Jespersen, J

    2000-01-01

    Ever since the coagulant activity of blood coagulation factor VII (FVII:C) was identified as a risk indicator of cardiac death, a large number of studies have measured FVII protein concentrations in plasma. FVII protein concentrations are either measured immunologically with an ELISA method (FVII...

  13. Effect of chitosan and coagulation factors on the wound repair phenotype of bioengineered blood clots.

    Science.gov (United States)

    Hoemann, Caroline D; Marchand, Catherine; Rivard, Georges-Etienne; El-Gabalawy, Hani; Poubelle, Patrice E

    2017-11-01

    Controlling the blood clot phenotype in a surgically prepared wound is an evolving concept in scaffold-guided tissue engineering. Here, we investigated the effect of added chitosan (80% or 95% Degree of Deacetylation, DDA) or coagulation factors (recombinant human Factor VIIa, Tissue Factor, thrombin) on inflammatory factors released by blood clots. We tested the hypothesis that 80% DDA chitosan specifically enhances leukotriene B 4 (LTB 4 ) production. Human or rabbit whole blood was combined with isotonic chitosan solutions, coagulation factors, or lipopolysaccharide, cultured in vitro at 37°C, and after 4hours the serum was assayed for LTB 4 or inflammatory factors. Only 80% DDA chitosan clots produced around 15-fold more LTB 4 over other clots including 95% DDA chitosan clots. All serum contained high levels of PDGF-BB and CXCL8. Normal clots produced very low type I cytokines compared to lipopolysaccharide clots, with even lower IL-6 and IL-12 and more CCL3/CCL4 produced by chitosan clots. Coagulation factors had no detectable effect on clot phenotype. Conclusion In blood clots from healthy individuals, 80% DDA chitosan has a unique influence of inducing more LTB 4 , a potent neutrophil chemoattractant, with similar production of PDGF-BB and CXCL8, and lower type I cytokines, compared to whole blood clots. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Rational and timely haemostatic interventions following cardiac surgery - coagulation factor concentrates or blood bank products.

    Science.gov (United States)

    Tang, Mariann; Fenger-Eriksen, Christian; Wierup, Per; Greisen, Jacob; Ingerslev, Jørgen; Hjortdal, Vibeke; Sørensen, Benny

    2017-06-01

    Cardiac surgery may cause a serious coagulopathy leading to increased risk of bleeding and transfusion demands. Blood bank products are commonly first line haemostatic intervention, but has been associated with hazardous side effect. Coagulation factor concentrates may be a more efficient, predictable, and potentially a safer treatment, although prospective clinical trials are needed to further explore these hypotheses. This study investigated the haemostatic potential of ex vivo supplementation of coagulation factor concentrates versus blood bank products on blood samples drawn from patients undergoing cardiac surgery. 30 adults were prospectively enrolled (mean age=63.9, females=27%). Ex vivo haemostatic interventions (monotherapy or combinations) were performed in whole blood taken immediately after surgery and two hours postoperatively. Fresh-frozen plasma, platelets, cryoprecipitate, fibrinogen concentrate, prothrombin complex concentrate (PCC), and recombinant FVIIa (rFVIIa) were investigated. The haemostatic effect was evaluated using whole blood thromboelastometry parameters, as well as by thrombin generation. Immediately after surgery the compromised maximum clot firmness was corrected by monotherapy with fibrinogen or platelets or combination therapy with fibrinogen. At two hours postoperatively the coagulation profile was further deranged as illustrated by a prolonged clotting time, a reduced maximum velocity and further diminished maximum clot firmness. The thrombin lagtime was progressively prolonged and both peak thrombin and endogenous thrombin potential were compromised. No monotherapy effectively corrected all haemostatic abnormalities. The most effective combinations were: fibrinogen+rFVIIa or fibrinogen+PCC. Blood bank products were not as effective in the correction of the coagulopathy. Coagulation factor concentrates appear to provide a more optimal haemostasis profile following cardiac surgery compared to blood bank products. Copyright © 2017

  15. Effect of nano-scale curvature on the intrinsic blood coagulation system

    Science.gov (United States)

    Kushida, Takashi; Saha, Krishnendu; Subramani, Chandramouleeswaran; Nandwana, Vikas; Rotello, Vincent M.

    2014-11-01

    The intrinsic coagulation activity of silica nanoparticles strongly depends on their surface curvature. Nanoparticles with higher surface curvature do not denature blood coagulation factor XII on its surface, providing a coagulation `silent' surface, while nanoparticles with lower surface curvature show denaturation and concomitant coagulation.The intrinsic coagulation activity of silica nanoparticles strongly depends on their surface curvature. Nanoparticles with higher surface curvature do not denature blood coagulation factor XII on its surface, providing a coagulation `silent' surface, while nanoparticles with lower surface curvature show denaturation and concomitant coagulation. Electronic supplementary information (ESI) available: Physical properties and scanning electron micrographs (SEM) of silica NPs, intrinsic coagulation activity after 3 h. See DOI: 10.1039/c4nr04128c

  16. Origin of serpin-mediated regulation of coagulation and blood pressure.

    Directory of Open Access Journals (Sweden)

    Yunjie Wang

    Full Text Available Vertebrates evolved an endothelium-lined hemostatic system and a pump-driven pressurized circulation with a finely-balanced coagulation cascade and elaborate blood pressure control over the past 500 million years. Genome analyses have identified principal components of the ancestral coagulation system, however, how this complex trait was originally regulated is largely unknown. Likewise, little is known about the roots of blood pressure control in vertebrates. Here we studied three members of the serpin superfamily that interfere with procoagulant activity and blood pressure of lampreys, a group of basal vertebrates. Angiotensinogen from these jawless fish was found to fulfill a dual role by operating as a highly selective thrombin inhibitor that is activated by heparin-related glycosaminoglycans, and concurrently by serving as source of effector peptides that activate type 1 angiotensin receptors. Lampreys, uniquely among vertebrates, thus use angiotensinogen for interference with both coagulation and osmo- and pressure regulation. Heparin cofactor II from lampreys, in contrast to its paralogue angiotensinogen, is preferentially activated by dermatan sulfate, suggesting that these two serpins affect different facets of thrombin's multiple roles. Lampreys also express a lineage-specific serpin with anti-factor Xa activity, which demonstrates that another important procoagulant enzyme is under inhibitory control. Comparative genomics suggests that orthologues of these three serpins were key components of the ancestral hemostatic system. It appears that, early in vertebrate evolution, coagulation and osmo- and pressure regulation crosstalked through antiproteolytically active angiotensinogen, a feature that was lost during vertebrate radiation, though in gnathostomes interplay between these traits is effective.

  17. Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases.

    Science.gov (United States)

    De Luca, Ciro; Virtuoso, Assunta; Maggio, Nicola; Papa, Michele

    2017-10-12

    Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix. The pleiotropy of these effects is produced through different receptors, expressed in various cell types, in a dose- and time-dependent pattern. We reviewed how these pathways may be involved in neurodegenerative diseases (amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases), multiple sclerosis, ischemic stroke and post-ischemic epilepsy, CNS cancer, addiction, and mental health. These data open up a new path for the potential therapeutic use of the agonist/antagonist of these proteins in the management of several central nervous system diseases.

  18. Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.

    Science.gov (United States)

    Mast, Alan E

    2016-01-01

    Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF-factor VIIa complexes that initiate blood coagulation. The TFPIα isoform is present in platelets. TFPIα contains a stretch of 9 amino acids nearly identical to those found in the B-domain of factor V that are well conserved in mammals. These amino acids provide exosite binding to activated factor V, which allows for TFPIα to inhibit prothrombinase during the initiation phase of blood coagulation. Endogenous inhibition at this point in the coagulation cascade was only recently recognized and has provided a biochemical rationale to explain the pathophysiological mechanisms underlying several clinical disorders. These include the east Texas bleeding disorder that is caused by production of an altered form of factor V with high affinity for TFPI and a paradoxical procoagulant effect of heparins. In addition, these findings have led to ideas for pharmacological targeting of TFPI that may reduce bleeding in hemophilia patients. © 2015 American Heart Association, Inc.

  19. A high fat meal activates blood coagulation factor vii in rats

    DEFF Research Database (Denmark)

    Olsen, A. K.; Bladbjerg, E. M.; Kornerup Hansen, A.

    2002-01-01

    In humans, high fat meals cause postprandial activation of blood coagulation factor VII (FVII), but human studies have not provided definite evidence for a prothrombotic effect of dietary FVII activation. An animal model would be an attractive way to pursue this question and therefore we tested...... the LEW/Mol rat. We gavaged 3 mL of a fat emulsion (n = 42) or 3 mL isotonic glucose (n = 42). Blood was sampled by heart puncture 2, 4 and 6 h (n = 14/group at each time) after the fat/glucose load. Furthermore, blood was sampled from 16 untreated rats to determine the baseline levels. Triglyceride...

  20. Evaluation of the efficacy and safety of rivaroxaban using a computer model for blood coagulation.

    Directory of Open Access Journals (Sweden)

    Rolf Burghaus

    Full Text Available Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist, enoxaparin (an indirect thrombin/Factor Xa inhibitor and dabigatran (a direct thrombin inhibitor. A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration-effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies.

  1. Effect of nano-scale curvature on the intrinsic blood coagulation system

    Science.gov (United States)

    Kushida, Takashi; Saha, Krishnendu; Subramani, Chandramouleeswaran; Nandwana, Vikas; Rotello, Vincent M.

    2014-01-01

    The intrinsic coagulation activity of silica nanoparticles strongly depends on their surface curvature. Nanoparticles with higher surface curvature do not denature blood coagulation factor XII on its surface, providing a coagulation ‘silent’ surface, while nanoparticles with lower surface curvature shows denaturation and concomitant coagulation. PMID:25341004

  2. Magnetic particle imaging of blood coagulation

    Energy Technology Data Exchange (ETDEWEB)

    Murase, Kenya, E-mail: murase@sahs.med.osaka-u.ac.jp; Song, Ruixiao; Hiratsuka, Samu [Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Osaka 565-0871 (Japan)

    2014-06-23

    We investigated the feasibility of visualizing blood coagulation using a system for magnetic particle imaging (MPI). A magnetic field-free line is generated using two opposing neodymium magnets and transverse images are reconstructed from the third-harmonic signals received by a gradiometer coil, using the maximum likelihood-expectation maximization algorithm. Our MPI system was used to image the blood coagulation induced by adding CaCl{sub 2} to whole sheep blood mixed with magnetic nanoparticles (MNPs). The “MPI value” was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. MPI values were significantly smaller for coagulated blood samples than those without coagulation. We confirmed the rationale of these results by calculating the third-harmonic signals for the measured viscosities of samples, with an assumption that the magnetization and particle size distribution of MNPs obey the Langevin equation and log-normal distribution, respectively. We concluded that MPI can be useful for visualizing blood coagulation.

  3. Should anti-inhibitor coagulant complex and tranexamic acid be used concomitantly?

    Science.gov (United States)

    Valentino, L A; Holme, P A

    2015-11-01

    Inhibitor development in haemophilia patients is challenging especially when undergoing surgical procedures. The development of an inhibitor precludes using factor VIII (FVIII) therapy thereby requiring a bypassing agent (BPA) for surgical bleeding prophylaxis if the FVIII inhibitor titre >5 BU. Concomitant use of anti-inhibitor coagulant complex (AICC) and tranexamic acid has been reported in the literature as a beneficial treatment for this population. Anti-inhibitor coagulant complex is known to cause an increase in thrombin generation and tranexamic acid inhibits fibrinolysis. Hence, the combined used of AICC and tranexamic acid has been limited due to safety concerns over possibilities of increased risk of thrombotic events and disseminated intravascular coagulation. However, the rationale for concomitant therapy is to obtain a potential synergistic effect and to increase clot stability. We conducted a literature review of past studies and individual case reports of concomitant use of AICC and tranexamic acid, which was extensively used during dental procedures. Evidence also exists for concomitant use of the combined therapy in orthopaedic procedures, control of gastrointestinal bleeding, epistaxis and cerebral haemorrhages. Some patients who received the combined therapy had failed monotherapy with a single BPA prior to combined therapy. There were no reports of thrombotic complications related to the concomitant therapy and haemostasis was achieved in all cases. Anti-inhibitor coagulant complex and tranexamic acid therapy was found to be safe, well-tolerated and effective therapy in haemophilia patients with inhibitors. Additional randomized controlled studies should be performed to confirm these findings. © 2015 John Wiley & Sons Ltd.

  4. Activation of factor VII bound to tissue factor: A key early step in the tissue factor pathway of blood coagulation

    International Nuclear Information System (INIS)

    Rao, L.V.M.; Rapaport, S.I.

    1988-01-01

    Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. The earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were made with purified factor VII, X, and tissue factor; in some experiments antithrombin III and heparin were added to prevent back-activation of factor VII. Factor X was activated at similar rates in reaction mixtures containing either VII or factor VIIa after an initial 30-sec lag with factor VII. In reaction mixtures with factor VII a linear activation of factor X was established several minutes before cleavage of 125 I-labeled factor VII to the two-chain activated molecule was demonstrable on gel profiles. These data suggest that factor VII/tissue factor cannot activate measurable amounts of factor X over several minutes. Overall, the results support the hypothesis that a rapid preferential activation of factor VII bound to tissue factor by trace amounts of factor Xa is a key early step in tissue factor-dependent blood coagulation

  5. Imaging of blood plasma coagulation at supported lipid membranes.

    Science.gov (United States)

    Faxälv, Lars; Hume, Jasmin; Kasemo, Bengt; Svedhem, Sofia

    2011-12-15

    The blood coagulation system relies on lipid membrane constituents to act as regulators of the coagulation process upon vascular trauma, and in particular the 2D configuration of the lipid membranes is known to efficiently catalyze enzymatic activity of blood coagulation factors. This work demonstrates a new application of a recently developed methodology to study blood coagulation at lipid membrane interfaces with the use of imaging technology. Lipid membranes with varied net charges were formed on silica supports by systematically using different combinations of lipids where neutral phosphocholine (PC) lipids were mixed with phospholipids having either positively charged ethylphosphocholine (EPC), or negatively charged phosphatidylserine (PS) headgroups. Coagulation imaging demonstrated that negatively charged SiO(2) and membrane surfaces exposing PS (obtained from liposomes containing 30% of PS) had coagulation times which were significantly shorter than those for plain PC membranes and EPC exposing membrane surfaces (obtained from liposomes containing 30% of EPC). Coagulation times decreased non-linearly with increasing negative surface charge for lipid membranes. A threshold value for shorter coagulation times was observed below a PS content of ∼6%. We conclude that the lipid membranes on solid support studied with the imaging setup as presented in this study offers a flexible and non-expensive solution for coagulation studies at biological membranes. It will be interesting to extend the present study towards examining coagulation on more complex lipid-based model systems. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Activation of factor VII bound to tissue factor: a key early step in the tissue factor pathway of blood coagulation.

    OpenAIRE

    Rao, L V; Rapaport, S I

    1988-01-01

    Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and factor IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. Our earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were ma...

  7. Blood coagulation in hemophilia A and hemophilia C

    NARCIS (Netherlands)

    Cawthern, K. M.; van 't Veer, C.; Lock, J. B.; DiLorenzo, M. E.; Branda, R. F.; Mann, K. G.

    1998-01-01

    Tissue factor (TF)-induced coagulation was compared in contact pathway suppressed human blood from normal, factor VIII-deficient, and factor XI-deficient donors. The progress of the reaction was analyzed in quenched samples by immunoassay and immunoblotting for fibrinopeptide A (FPA),

  8. A ¤high-fat meal does not activate blood coagulation factor vii in minipigs

    DEFF Research Database (Denmark)

    Olsen, A. K.; Larsen, L. F.; Bladbjerg, E.-M.

    2001-01-01

    It is a matter of debate whether postprandial activation of blood coagulation factor VII (FVII) is associated with an increased risk of thrombosis. To clarify this question, an animal model in which consequences of dietary FVII activation can be studied in a more detailed way would be an important...

  9. Biomarkers of coagulation, fibrinolysis, endothelial function, and inflammation in arterialized venous blood

    DEFF Research Database (Denmark)

    Gram, Anne Sofie; Skov, Jane; Ploug, Thorkil

    2014-01-01

    Effects of venous blood arterialization on cardiovascular risk markers are still unknown. We evaluated biomarkers of inflammation, coagulation, fibrinolysis, and endothelial function in arterialized compared with regular venous blood. Cubital venipunctures were obtained from 10 healthy volunteers....... Arterialization was generated by 10 min heating of the contralateral hand. Concentrations of albumin, C-reactive protein (CRP), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), and von Willebrand factor (vWF) were measured by validated assays. Concentrations of albumin......, CRP, and vWF were significantly lower in arterialized than in venous blood (albumin: 43.8 g/l and 44.8 g/l, P = 0.02). Differences in CRP and vWF became insignificant after adjusting for albumin. The endogenous thrombin potential (ETP) was significantly higher in arterialized than in venous blood...

  10. Tissue factor-dependent blood coagulation is enhanced following delivery irrespective of the mode of delivery

    NARCIS (Netherlands)

    Boer, K.; den Hollander, I. A.; Meijers, J. C. M.; Levi, M. [=Marcel M.

    2007-01-01

    BACKGROUND: The risk of thrombosis is clearly increased in the postpartum period. Mice with a targeted deletion of the transmembrane domain of tissue factor (TF) develop serious activation of blood coagulation and widespread thrombosis after delivery. OBJECTIVE AND METHODS: We hypothesized that TF,

  11. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    International Nuclear Information System (INIS)

    Tormoen, Garth W; Khader, Ayesha; Gruber, András; McCarty, Owen J T

    2013-01-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis. (paper)

  12. Purification and characterization of a heteromultimeric glycoprotein from Artocarpus heterophyllus latex with an inhibitory effect on human blood coagulation.

    Science.gov (United States)

    Siritapetawee, Jaruwan; Thammasirirak, Sompong

    2011-01-01

    Plant latex has many health benefits and has been used in folk medicine. In this study, the biological effect of Artocarpus heterophyllus (jackfruit) latex on human blood coagulation was investigated. By a combination of heat precipitation and ion-exchange chromatography, a heat stable heteromultimeric glycoprotein (HSGPL1) was purified from jackfruit milky latex. The apparent molecular masses of the monomeric proteins on SDS/PAGE were 33, 31 and 29 kDa. The isoelectric points (pIs) of the monomers were 6.63, 6.63 and 6.93, respectively. Glycosylation and deglycosylation tests confirmed that each subunit of HSGPL1 formed the native multimer by sugar-based interaction. Moreover, the multimer of HSGPL1 also resisted 2-mercaptoethanol action. Peptide mass fingerprint analysis indicated that HSGPL1 was a complex protein related to Hsps/chaperones. HSGPL1 has an effect on intrinsic pathways of the human blood coagulation system by significantly prolonging the activated partial thrombin time (APTT). In contrast, it has no effect on the human extrinsic blood coagulation system using the prothrombin time (PT) test. The prolonged APTT resulted from the serine protease inhibitor property of HSGPL1, since it reduced activity of human blood coagulation factors XI(a) and α-XII(a).

  13. Evaluation of coagulation factors and platelet function from an off-line modified ultrafiltration technique for post-cardiopulmonary bypass circuit blood recovery.

    Science.gov (United States)

    Beckmann, S; Lynn, P; Miller, S; Harris, R; DiMarco, R F; Ross, J E

    2013-05-01

    Modified ultrafiltration (MUF) is a technique that hemoconcentrates residual CPB circuit blood and the patient at the same time. Hemoconcentration and MUF are Class 1-A recommendations in the anesthesia and surgical blood conservation guidelines. This study evaluated the off-line MUF process of the Hemobag (HB, Global Blood Resources, Somers, CT, USA) to quantitate coagulation factor levels, platelet (PLT) count and function in one facility and cellular growth factor concentrations of the final product that were transfused to the patient in another facility In two cardiac surgery facilities, after decannulation, the extracorporeal circuit (ECC) blood from 22 patients undergoing cardiac surgery was processed with the HB device. In eleven patients from the first facility by the study design, blood samples for coagulation factor levels and PLT aggregation were drawn from the reservoir of the MUF device pre- and post-processing. The samples (n = 11) were sent to a reference laboratory where testing for prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), reptilase time, fibrinogen, clotting factors II, V, VII, VIII, IX, X, ADAMTS-13, protein C, protein S, antithrombin III, von Willebrand Factor (vWF), and platelet (PLT) aggregation were performed. A portion of the final concentrated HB blood samples (n = 5-10) from the second facility by design were evaluated for transforming and platelet-derived cellular growth factor concentrations. On average, approximately 800 - 2000 mls of whole blood were removed from the ECC post-CPB for processing in the HB device. After processing, there was, on the average, approximately 300 - 950 mls of concentrated whole blood salvaged for reinfusion. The PT and INR were significantly lower in the post-processing product compared to the pre-processing samples while the aPTT times were not significantly different. All coagulation factors and natural anti-coagulants were significantly

  14. Contact activation of blood-plasma coagulation

    Science.gov (United States)

    Golas, Avantika

    Surface engineering of biomaterials with improved hemocompatibility is an imperative, given the widespread global need for cardiovascular devices. Research summarized in this dissertation focuses on contact activation of FXII in buffer and blood plasma frequently referred to as autoactivation. The extant theory of contact activation imparts FXII autoactivation ability to negatively charged, hydrophilic surfaces. According to this theory, contact activation of plasma involves assembly of proteins comprising an "activation complex" on activating surfaces mediated by specific chemical interactions between complex proteins and the surface. This work has made key discoveries that significantly improve our core understanding of contact activation and unravel the existing paradigm of plasma coagulation. It is shown herein that contact activation of blood factor XII (FXII, Hageman factor) in neat-buffer solution exhibits a parabolic profile when scaled as a function of silanized-glass-particle activator surface energy (measured as advancing water adhesion tension t°a=g° Iv costheta in dyne/cm, where g°Iv is water interfacial tension in dyne/cm and theta is the advancing contact angle). Nearly equal activation is observed at the extremes of activator water-wetting properties --36 moderated by adsorption of plasma proteins unrelated to coagulation through an "adsorption-dilution" effect that blocks FXII contact with hydrophobic activator surfaces. The adsorption-dilution effect explains the apparent specificity for hydrophilic activators pursued by earlier investigators. Finally a comparison of FXII autoactivation in buffer, serum, protein cocktail, and plasma solutions is shown herein. Activation of blood plasma coagulation in vitro by contact with material surfaces is demonstrably dependent on plasma-volume-to-activator-surface-area ratio. However, activation of factor XII dissolved in buffer, protein cocktail, heat-denatured serum, and FXI deficient plasma does not

  15. Numerical Simulation of the Coagulation Dynamics of Blood

    Directory of Open Access Journals (Sweden)

    T. Bodnár

    2008-01-01

    Full Text Available The process of platelet activation and blood coagulation is quite complex and not yet completely understood. Recently, a phenomenological meaningful model of blood coagulation and clot formation in flowing blood that extends existing models to integrate biochemical, physiological and rheological factors, has been developed. The aim of this paper is to present results from a computational study of a simplified version of this coupled fluid-biochemistry model. A generalized Newtonian model with shear-thinning viscosity has been adopted to describe the flow of blood. To simulate the biochemical changes and transport of various enzymes, proteins and platelets involved in the coagulation process, a set of coupled advection–diffusion–reaction equations is used. Three-dimensional numerical simulations are carried out for the whole model in a straight vessel with circular cross-section, using a finite volume semi-discretization in space, on structured grids, and a multistage scheme for time integration. Clot formation and growth are investigated in the vicinity of an injured region of the vessel wall. These are preliminary results aimed at showing the validation of the model and of the numerical code.

  16. Anticoagulant activity in salivary glands of the insect vector Culicoides variipennis sonorensis by an inhibitor of factor Xa.

    Science.gov (United States)

    Pérez de León, A A; Valenzuela, J G; Tabachnick, W J

    1998-02-01

    Blood feeding by the insect vector Culicoides variipennis sonorensis involves laceration of superficial host tissues, an injury that would be expected to trigger the coagulation cascade. Accordingly, the salivary glands of C.v. sonorensis were examined for the presence of an antihemostatic that prevents blood coagulation. Assays using salivary gland extracts showed a delay in the recalcification time of plasma devoid of platelets, indicating the presence of anticoagulant activity. Retardation in the formation of a fibrin clot was also observed after the addition of tissue factor to plasma that was preincubated with salivary gland extracts. Similarly, an inhibitory effect by salivary gland extracts was detected in assays that included factors of the intrinsic pathway. Inhibition of the catalytic activity of purified factor Xa toward its chromogenic substrate suggested that it was the target of the salivary anticoagulant of C.v. sonorensis. This was corroborated by the coincidence of anticoagulant and anti-FXa activities obtained by reverse-phase HPLC. The depletion of anti-FXa activity from salivary glands during blood feeding suggests that the FXa inhibitor functions as anticoagulant. Molecular sieving HPLC yielded an apparent molecular mass of 28 kDa for the salivary FXa inhibitor of C.v. sonorensis. Preventing the formation of thrombin through the inhibition of FXa likely facilitates blood feeding by maintaining the pool of blood fluid at the feeding site. The salivary FXa inhibitor of C.v. sonorensis could impair the network of host-defense mechanisms in the skin microenvironment by avoiding blood coagulation at the site of feeding.

  17. Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells

    OpenAIRE

    Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

    2009-01-01

    Background: Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian ca...

  18. [Coagulation factor VII levels in uremic patients and theirs influence factors].

    Science.gov (United States)

    Fang, Jun; Xia, Ling-Hui; Wei, Wen-Ning; Song, Shan-Jun

    2004-12-01

    This study was aimed to investigate coagulation factor VII level in uremic patients with chronic renal failure and to explore theirs influence factors. The plasma levels of coagulation factor VII were detected in 30 uremic patients with chronic renal failure before and after hemodialysis for 1 month, the factor VII activity (FVII:C) was determined by one-stage coagulation method, while activated factor VII (FVIIa) was measured by one-stage coagulation method using recombinant soluble tissue factor, and factor VII antigen was detected by ELISA. The results showed that: (1) The FVIIa, FVII:C and FVIIAg levels in chronic uremic patients before hemodialysis were 4.00 +/- 0.86 microg/L, (148.5 +/- 40.4)% and (99.8 +/- 21.1)% respectively, which were significantly increased, as compared with healthy controls [2.77 +/- 1.02 microg/L, (113.1 +/- 33.0)% and (73.7 +/- 18.3)% respectively, P factor VII was positively correlated with levels of blood uria nitrogen and serum creatinine before hemodialysis but not after hemodialysis. It is concluded that the enhanced levels of coagulation factor VII in chronic uremic patients suggested abnormal activated state, herperactivity and elevated production of factor VII which correlated with renal functional injury. The abnormality of factor VII in uremia may be aggravated by hemodialysis. Coagulation factor (FVII) may be a risk factor for cardiovascular events in uremic patients who especially had been accepted long-term hemodialysis.

  19. Effects of dietary fat quality and quantity on postprandial activation of blood coagulation factor VII

    DEFF Research Database (Denmark)

    Larsen, L. F.; Bladbjerg, E.-M.; Jespersen, J.

    1997-01-01

    , monounsaturated, or polyunsaturated fats differed regarding postprandial activation of FVII. Eighteen healthy young men participated in the study. On 6 separate days each participant consumed two meals (times, 0 and 1 3/4 hours) enriched with 70 g (15 and 55 g) of either rapeseed oil, olive oil, sunflower oil......, palm oil, or butter (42% of energy from fat) or isoenergetic low-fat meals (6% of energy from fat). Fasting and series of nonfasting blood samples (the last at time 8 1/2 hours) were collected. Plasma triglycerides, FVIIc, FVIIa, and free fatty acids were analyzed. There were marked effects of the fat......Acute elevation of the coagulant activity of blood coagulation factor VII (FVIIc) is observed after consumption of high-fat meals. This elevation is caused by an increase in the concentration of activated FVII (FVIIa). In a randomized crossover study, we investigated whether saturated...

  20. A review of studies of the activation of the blood coagulation mechanism in chimpanzees (Pan troglodytes)

    NARCIS (Netherlands)

    ten Cate, H.; Schenk, B. E.; Biemond, B. J.; Levi, M. [=Marcel M.; van der Poll, T.; Buller, H. R.; ten Cate, J. W.

    1994-01-01

    This paper reviews our recent studies of blood coagulation activation in the chimpanzee which were carried out employing sensitive immunoassays that measure activation markers of blood coagulation in plasma. Infused factor VIIa activated both factors IX and X in vivo; this reaction depended on the

  1. In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. possible implications for measurements in vivo after heparin therapy

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Larsen, L F; Ostergaard, P

    2000-01-01

    The coagulant activity of blood coagulation factor VII (FVII:C) can be lowered by changes in lifestyle and by therapeutic intervention, e.g. heparin infusion. The question is, however, whether FVII:C determined ex vivo is a valid measure of the FVII activity in vivo. We measured plasma FVII......:C, activated FVII (FVIIa), FVII protein (FVII:Ag), tissue factor pathway inhibitor (TFPI), triglycerides, and free fatty acids (FFA) before and 15 min after infusion of a bolus of unfractionated heparin (50 IU/kg body weight) in 12 healthy subjects. Additionally, we conducted in vitro experiments...

  2. Blood coagulation and the risk of atherothrombosis: a complex relationship

    Directory of Open Access Journals (Sweden)

    van der Voort Danielle

    2004-12-01

    Full Text Available Abstract The principles of Virchov's triad appear to be operational in atherothrombosis or arterial thrombosis: local flow changes and particularly vacular wall damage are the main pathophysiological elements. Furthermore, alterations in arterial blood composition are also involved although the specific role and importance of blood coagulation is an ongoing matter of debate. In this review we provide support for the hypothesis that activated blood coagulation is an essential determinant of the risk of atherothrombotic complications. We distinguish two phases in atherosclerosis: In the first phase, atherosclerosis develops under influence of "classical" risk factors, i.e. both genetic and acquired forces. While fibrinogen/fibrin molecules participate in early plaque lesions, increased activity of systemic coagulation is of no major influence on the risk of arterial thrombosis, except in rare cases where a number of specific procoagulant forces collide. Despite the presence of tissue factorfactor VII complex it is unlikely that all fibrin in the atherosclerotic plaque is the direct result from local clotting activity. The dominant effect of coagulation in this phase is anticoagulant, i.e. thrombin enhances protein C activation through its binding to endothelial thrombomodulin. The second phase is characterized by advancing atherosclerosis, with greater impact of inflammation as indicated by an elevated level of plasma C-reactive protein, the result of increased production influenced by interleukin-6. Inflammation overwhelms protective anticoagulant forces, which in itself may have become less efficient due to down regulation of thrombomodulin and endothelial cell protein C receptor (EPCR expression. In this phase, the inflammatory drive leads to recurrent induction of tissue factor and assembly of catalytic complexes on aggregated cells and on microparticles, maintaining a certain level of thrombin production and fibrin formation. In advanced

  3. Bio-responsive polymer hydrogels homeostatically regulate blood coagulation.

    Science.gov (United States)

    Maitz, Manfred F; Freudenberg, Uwe; Tsurkan, Mikhail V; Fischer, Marion; Beyrich, Theresa; Werner, Carsten

    2013-01-01

    Bio-responsive polymer architectures can empower medical therapies by engaging molecular feedback-response mechanisms resembling the homeostatic adaptation of living tissues to varying environmental constraints. Here we show that a blood coagulation-responsive hydrogel system can deliver heparin in amounts triggered by the environmental levels of thrombin, the key enzyme of the coagulation cascade, which--in turn--becomes inactivated due to released heparin. The bio-responsive hydrogel quantitatively quenches blood coagulation over several hours in the presence of pro-coagulant stimuli and during repeated incubation with fresh, non-anticoagulated blood. These features enable the introduced material to provide sustainable, autoregulated anticoagulation, addressing a key challenge of many medical therapies. Beyond that, the explored concept may facilitate the development of materials that allow the effective and controlled application of drugs and biomolecules.

  4. Synthesis of Phosphatidylserine and Its Stereoisomers: Their Role in Activation of Blood Coagulation.

    Science.gov (United States)

    Mallik, Suman; Prasad, Ramesh; Bhattacharya, Anindita; Sen, Prosenjit

    2018-05-10

    Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein-lipid interactions.

  5. [The pathogenesis of subclinical laminitis in dairy cattle: studies of the hoof status, rumen status and blood coagulation factors].

    Science.gov (United States)

    Brandejsky, F; Stanek, C; Schuh, M

    1994-02-01

    In 50 dairy cows of the breed "Braunvieh" (36 heifers, 14 cows) of one herd the claw score was recorded over a period of 2 months before parturition until 6 months after parturition. The claw scores were correlated with the clinical findings, the ruminal function and the blood coagulation factors calcium-thromboplastin (TPZ), partial thromboplastin time (PTT), thrombin time (TZ) and antithrombin III (AT III) evaluated one day and one week after calving. The claw score increased from the first to the second examination, remaining on the same level in the postpartal period. No correlation between the claw scores and the ruminal function was evident. In comparison with a control group, TPZ and PTT were found higher one day and one week after parturition in the experimental group. Blood coagulation factors and claw scores were found uncorrelated.

  6. EVALUATION OF PERIODONTAL TISSUES CONDITION IN CHILDREN WITH BLOOD COAGULABILITY PATHOLOGY

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    M. A. Gavrilenko

    2013-12-01

    Full Text Available Background. Actuality of the problem is determined by the high prevalence of inflammatory diseases of periodontal tissues in children with blood pathology (100%. Primary prevention of dental caries and periodontal diseases has the exceptional importance in the dentist’s work with children who have blood coagulability disorders. Prevention of dental diseases of the oral cavity in this category of patients has a number of features because there is the risk of bleeding during both home oral hygiene and professional hygiene. Exogenous prevention (fluoride-containing gels, varnishes, solutions, sealants also has its own peculiarities in these children. On the other hand, the impossibility of preventive measures implementation is the significant factor in the pathogenesis of gingivitis and subsequently periodontitis in children with disorders of blood coagulability. Aim. To examine the status of oral hygiene in children with blood coagulability disorders. To examine the severity of inflammatory and destructive changes in the periodontal tissues in children with disorders of blood coagulability. To investigate timing and frequency of oral hygiene implementation in children with disorders of blood coagulability. To reveal the interrelations between the intensity, prevalence of periodontal tissues disorders in children with blood coagulability pathology and the periods of tooth development, taking into account the influence of risk factors and frequency of oral hygiene. Materials and methods. 120 children between 2 and 18 years old with blood coagulability disorders (hemophilia A, B, thrombocytopenia, thrombocytopathy were examined. Children were divided into following age groups: I – 2-5 years old (40 children, II – 6-10 years old (40 children, III – 11-18 years old (40 children, according to the periods of tooth development, with an equal number of children in groups according to diagnoses. Hygiene index value was determined according to

  7. Evaluation of periodontal tissues condition in children with blood coagulability pathology

    Directory of Open Access Journals (Sweden)

    M. A. Gavrilenko

    2013-12-01

    Full Text Available Background. Actuality of the problem is determined by the high prevalence of inflammatory diseases of periodontal tissues in children with blood pathology (100%. Primary prevention of dental caries and periodontal diseases has the exceptional importance in the dentist’s work with children who have blood coagulability disorders. Prevention of dental diseases of the oral cavity in this category of patients has a number of features because there is the risk of bleeding during both home oral hygiene and professional hygiene. Exogenous prevention (fluoride-containing gels, varnishes, solutions, sealants also has its own peculiarities in these children. On the other hand, the impossibility of preventive measures implementation is the significant factor in the pathogenesis of gingivitis and subsequently periodontitis in children with disorders of blood coagulability. Aim.To examine the status of oral hygiene in children with blood coagulability disorders.To examine the severity of inflammatory and destructive changes in the periodontal tissues in children with disorders of blood coagulability. To investigate timing and frequency of oral hygiene implementation in children with disorders of blood coagulability. To reveal the interrelations between the intensity, prevalence of periodontal tissues disorders in children with blood coagulability pathology and the periods of tooth development, taking into account the influence of risk factors and frequency of oral hygiene. Materials and methods. 120 children between 2 and 18 years old with blood coagulability disorders (hemophilia A, B, thrombocytopenia, thrombocytopathy were examined. Children were divided into following age groups: I – 2-5 years old (40 children, II – 6-10 years old (40 children, III – 11-18 years old (40 children, according to the periods of tooth development, with an equal number of children in groups according to diagnoses. Hygiene index value was determined according to Fedorov

  8. Untangling the complexity of blood coagulation network: use of computational modelling in pharmacology and diagnostics.

    Science.gov (United States)

    Shibeko, Alexey M; Panteleev, Mikhail A

    2016-05-01

    Blood coagulation is a complex biochemical network that plays critical roles in haemostasis (a physiological process that stops bleeding on injury) and thrombosis (pathological vessel occlusion). Both up- and down-regulation of coagulation remain a major challenge for modern medicine, with the ultimate goal to correct haemostasis without causing thrombosis and vice versa. Mathematical/computational modelling is potentially an important tool for understanding blood coagulation disorders and their treatment. It can save a huge amount of time and resources, and provide a valuable alternative or supplement when clinical studies are limited, or not ethical, or technically impossible. This article reviews contemporary state of the art in the modelling of blood coagulation for practical purposes: to reveal the molecular basis of a disease, to understand mechanisms of drug action, to predict pharmacodynamics and drug-drug interactions, to suggest potential drug targets or to improve quality of diagnostics. Different model types and designs used for this are discussed. Functional mechanisms of procoagulant bypassing agents and investigations of coagulation inhibitors were the two particularly popular applications of computational modelling that gave non-trivial results. Yet, like any other tool, modelling has its limitations, mainly determined by insufficient knowledge of the system, uncertainty and unreliability of complex models. We show how to some extent this can be overcome and discuss what can be expected from the mathematical modelling of coagulation in not-so-far future. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. Effect of Dan seven soft capsule adjuvant therapy on serum inflammatory factors, coagulation function and blood rheology indexes in patients with acute hemorrhagic cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    Shu-Hua Gui

    2017-08-01

    Full Text Available Objective: To investigate the effect of Dan seven soft capsule on the treatment of acute hemorrhagic cerebrovascular disease and the influence of serum inflammatory factors, coagulation function and blood rheology indexes. Methods: A total of 112 cases of patients with acute hemorrhagic cerebrovascular disease, according to the random data table were divided into the control group (n=57 and observation group (n=55, the patients in the control group received routine treatment combined with edaravone, on the basis of the treatment of the control group, the observation group was treated with Dan seven soft capsule. The serum levels of inflammatory factors, coagulation function and blood rheology indexes were compared between the two groups before and after treatment. Results: Before treatment, there were no significant difference in the inflammatory factors (hs-CRP, TNF-α and IL-6, blood coagulation function (FIB, PT and APTT and hemorheology (high cut whole blood viscosity, low cut whole blood viscosity and plasma viscosity levels between the control group and observation group. Compared with the levels of the same group before treatment, two groups of hs-CRP, TNF-α, IL-6, FIB, high cut whole blood viscosity, low cut whole blood viscosity and plasma viscosity level after treatment were significantly decreased, and levels in the observation group were significantly lower than those in the control group; Compared with the group before treatment, the levels of PT and APTT in the two groups were significantly increased, and the observation group was significantly higher than the control group. Conclusion: Dan seven soft capsule in the treatment of acute hemorrhagic cerebrovascular disease can effectively reduce the level of serum inflammatory factors, improve coagulation function and blood rheology index, it has an important clinical value.

  10. Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment.

    Science.gov (United States)

    Yu, Yuanjie; Böing, Anita N; Hau, Chi M; Hajji, Najat; Ruf, Wolfram; Sturk, Auguste; Nieuwland, Rienk

    2018-06-01

     Tissue factor (TF) can be present in a non-coagulant and coagulant form. Whether the coagulant activity is affected by the plasma membrane microenvironment is unexplored.  This article studies the presence and coagulant activity of human TF in plasma membrane micro-domains.  Plasma membranes were isolated from human MIA PaCa2 cells, MDA-MB-231 cells and human vascular smooth muscle cells by Percoll gradient ultracentrifugation after cell disruption. Plasma membranes were fractionated by OptiPrep gradient ultracentrifugation, and the presence of TF, flotillin, caveolin, clathrin, protein disulphide isomerase (PDI), TF pathway inhibitor (TFPI) and phosphatidylserine (PS) were determined.  Plasma membranes contain two detergent-resistant membrane (DRM) compartments differing in density and biochemical composition. High-density DRMs (DRM-H) have a density ( ρ ) of 1.15 to 1.20 g/mL and contain clathrin, whereas low-density DRMs (DRM-L) have a density between 1.09 and 1.13 g/mL and do not contain clathrin. Both DRMs contain TF, flotillin and caveolin. PDI is detectable in DRM-H, TFPI is not detectable in either DMR-H or DRM-L and PS is detectable in DRM-L. The DRM-H-associated TF (> 95% of the TF antigen) lacks detectable coagulant activity, whereas the DRM-L-associated TF triggers coagulation. This coagulant activity is inhibited by lactadherin and thus PS-dependent, but seemed insensitive to 16F16, an inhibitor of PDI.  Non-coagulant and coagulant TF are present within different types of DRMs in the plasma membrane, and the composition of these DRMs may affect the TF coagulant activity. Schattauer GmbH Stuttgart.

  11. Benign intracranial hypertension associated to blood coagulation derangements

    Directory of Open Access Journals (Sweden)

    Niglio Alferio

    2006-12-01

    Full Text Available Abstract Background Benign Intracranial Hypertension (BIH may be caused, at least in part, by intracranial sinus thrombosis. Thrombosis is normally due to derangements in blood coagulation cascade which may predispose to abnormal clotting activation or deficiency in natural inhibitors' control. The aim of the study is to examine the strength of the association between risk factors for thrombosis and BIH. Patients and methods The incidence of prothrombotic abnormalities among a randomly investigated cohort of 17 patients with BIH, was compared with 51 healthy subjects matched for sex, age, body mass index, height and social background. Results The number of subjects with protein C deficiency was significantly higher in patients than in controls (3 vs 1, p Increased plasma levels of prothrombin fragment 1+2, fibrinopeptide A (FPA, and PAI-1 were demonstrated in patients group (5.7 ± 1.15 nM vs 0.45 ± 0.35 nM; 8.7 ± 2.5 ng/mL vs 2.2 ± 1.25 ng/mL; 45.7 ± 12.5 ng/mL vs 8.5 ± 6.7 ng/mL, respectively; p Discussion In agreement with other authors our data suggest a state of hypercoagulability in BIH associated with gene polymorphisms. Our findings also showed that mutations in cardiovascular genes significantly discriminate subjects with a BIH history. The association between coagulation and gene derangements, usually regarded to as cryptogenic, may suggest a possible pathogenetic mechanism in BIH. So, a prothrombotic tendency may exist that would, at least in part, explain some cases of BIH. Although based on a small population, these findings raise the exciting possibility of using these haemostatic factors as markers for selecting high-risk subjects in BIH disease.

  12. Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI.

    Directory of Open Access Journals (Sweden)

    Cristina Puy

    Full Text Available Factor (F XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα, in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin.Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma.Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP.

  13. Nanoparticles and the blood coagulation system. Part I: benefits of nanotechnology.

    Science.gov (United States)

    Ilinskaya, Anna N; Dobrovolskaia, Marina A

    2013-05-01

    Nanotechnology is proven to provide certain benefits in drug delivery by improving solubility, increasing uptake to target sites and changing pharmacokinetics profiles of traditional drugs. Since properties of many materials change tremendously at the nanoscale levels, nanotechnology is also being explored in various industrial applications. As such, nanoparticles are rapidly entering various areas of industry, biology and medicine. The benefits of using nanotechnology for industrial and biomedical applications are often tempered by concerns about the safety of these new materials. One such area of concern includes their effect on the immune system. While nanoparticle interactions with various constituents of the immune system have been reviewed before, little attention was given to nanoparticle effects on the blood coagulation system. Nanoparticle interface with the blood coagulation system may lead to either benefits to the host or adverse reactions. This article reviews recent advances in our understanding of nanoparticle interactions with plasma coagulation factors, platelets, endothelial cells and leukocytes. Part I is focused on desirable interactions between nanoparticles and the coagulation system, and discusses benefits of using nanotechnology to intervene in coagulation disorders. Undesirable interactions posing safety concerns are covered in part II, which will be published in the June issue of Nanomedicine.

  14. Extensive small-angle X-ray scattering studies of blood coagulation factor VIIa reveal interdomain flexibility

    DEFF Research Database (Denmark)

    Mosbæk, Charlotte Rode; Nolan, David; Persson, Egon

    2010-01-01

    Blood coagulation factor VIIa (FVIIa) is used in the treatment of replacement therapy resistant hemophilia patients, and FVIIa is normally activated upon complex formation with tissue factor (TF), potentially in context with structural rearrangements. The solution behavior of uncomplexed FVIIa...... is important for understanding the mechanism of activation and for the stability and activity of the pharmaceutical product. However, crystal structures of FVIIa in complex with TF and of truncated free FVIIa reveal different overall conformations while previous small-angle scattering studies suggest FVIIa...... causing resistance to activation, thereby emphasizing the connection between the distribution of different conformations of FVII and the mechanism of activation....

  15. Modelling of the Blood Coagulation Cascade in an In Vitro Flow System

    DEFF Research Database (Denmark)

    Andersen, Nina Marianne; Sørensen, Mads Peter; Efendiev, Messoud A.

    2010-01-01

    We derive a mathematical model of a part of the blood coagulation cascade set up in a perfusion experiment. Our purpose is to simulate the influence of blood flow and diffusion on the blood coagulation pathway. The resulting model consists of a system of partial differential equations taking...... and flow equations, which guarantee non negative concentrations at all times. The criteria is applied to the model of the blood coagulation cascade....

  16. Characterization of a human coagulation factor Xa-binding site on Viperidae snake venom phospholipases A2 by affinity binding studies and molecular bioinformatics

    Directory of Open Access Journals (Sweden)

    Gowda Veerabasappa T

    2007-12-01

    Full Text Available Abstract Background The snake venom group IIA secreted phospholipases A2 (SVPLA2, present in the Viperidae snake family exhibit a wide range of toxic and pharmacological effects. They exert their different functions by catalyzing the hydrolysis of phospholipids (PL at the membrane/water interface and by highly specific direct binding to: (i presynaptic membrane-bound or intracellular receptors; (ii natural PLA2-inhibitors from snake serum; and (iii coagulation factors present in human blood. Results Using surface plasmon resonance (SPR protein-protein interaction measurements and an in vitro biological test of inhibition of prothrombinase activity, we identify a number of Viperidae venom SVPLA2s that inhibit blood coagulation through direct binding to human blood coagulation factor Xa (FXa via a non-catalytic, PL-independent mechanism. We classify the SVPLA2s in four groups, depending on the strength of their binding. Molecular electrostatic potentials calculated at the surface of 3D homology-modeling models show a correlation with inhibition of prothrombinase activity. In addition, molecular docking simulations between SVPLA2 and FXa guided by the experimental data identify the potential FXa binding site on the SVPLA2s. This site is composed of the following regions: helices A and B, the Ca2+ loop, the helix C-β-wing loop, and the C-terminal fragment. Some of the SVPLA2 binding site residues belong also to the interfacial binding site (IBS. The interface in FXa involves both, the light and heavy chains. Conclusion We have experimentally identified several strong FXa-binding SVPLA2s that disrupt the function of the coagulation cascade by interacting with FXa by the non-catalytic PL-independent mechanism. By theoretical methods we mapped the interaction sites on both, the SVPLA2s and FXa. Our findings may lead to the design of novel, non-competitive FXa inhibitors.

  17. The involvement of ginseng berry extract in blood flow via regulation of blood coagulation in rats fed a high-fat diet

    Directory of Open Access Journals (Sweden)

    Min Hee Kim

    2017-04-01

    Conclusion: These results suggest the possibility that GBx can ameliorate blood flow by decreasing intima-media thickness via the regulation of blood coagulation factors related to lipid metabolites in rats fed a HFD.

  18. Effect of fibrinogen on blood coagulation detected by optical coherence tomography

    International Nuclear Information System (INIS)

    Xu, Xiangqun; Teng, Xiangshuai

    2015-01-01

    Our previous work demonstrated that an optical coherence tomography (OCT) technique and the parameter 1/e light penetration depth (d 1/e ) were able to characterize the whole blood coagulation process in contrast to existing optical tests that are performed on plasma samples. To evaluate the feasibility of the technique for quantifying the effect of fibrinogen (Fbg) on blood coagulation, a dynamic study of d 1/e of blood in various Fbg concentrations was performed in static state. Two groups of blood samples of hematocrit (HCT) in 35, 45, and 55% were reconstituted of red blood cells with: 1) treated plasma with its intrinsic Fbg removed and commercial Fbg added (0–8 g L −1 ); and 2) native plasma with commercial Fbg added (0–8 g L −1 ). The results revealed a typical behavior due to coagulation induced by calcium ions and the clotting time is Fbg concentration-dependent. The clotting time was decreased by the increasing amount of Fbg in both groups. Besides, the blood of lower HCT with various levels of Fbg took shorter time to coagulate than that of higher HCT. Consequently, the OCT method is a useful and promising tool for the detection of blood-coagulation processes induced with different Fbg levels. (paper)

  19. Blood viscosity during coagulation at different shear rates

    Science.gov (United States)

    Ranucci, Marco; Laddomada, Tommaso; Ranucci, Matteo; Baryshnikova, Ekaterina

    2014-01-01

    Abstract During the coagulation process, blood changes from a liquid to a solid gel phase. These changes are reflected by changes in blood viscosity; however, blood viscosity at different shear rates (SR) has not been previously explored during the coagulation process. In this study, we investigated the viscosity changes of whole blood in 10 subjects with a normal coagulation profile, using a cone‐on‐plate viscosimeter. For each subject, three consecutive measurements were performed, at a SR of 20, 40, 80 sec−1. On the basis of the time‐dependent changes in blood viscosity, we identified the gel point (GP), the time‐to‐gel point (TGP), the maximum clot viscosity (MCV), and the clot lysis half‐time (CLH). The TGP significantly (P = 0.0023) shortened for increasing SR, and was significantly associated with the activated partial thromboplastin time at a SR of 20 sec−1 (P = 0.038) and 80 sec−1 (P = 0.019). The MCV was significantly lower at a SR of 80 sec−1 versus 40 sec−1 (P = 0.027) and the CLH significantly (P = 0.048) increased for increasing SR. These results demonstrate that measurement of blood viscosity during the coagulation process offers a number of potentially useful parameters. In particular, the association between the TGP and the activated partial thromboplastin time is an expression of the clotting time (intrinsic and common pathway), and its shortening for increasing SR may be interpreted the well‐known activating effects of SR on platelet activation and thrombin generation. Further studies focused on the TGP under conditions of hypo‐ or hypercoagulability are required to confirm its role in the clinical practice. PMID:24994896

  20. Blood coagulation abnormalities in multibacillary leprosy patients.

    Science.gov (United States)

    Silva, Débora Santos da; Teixeira, Lisandra Antonia Castro; Beghini, Daniela Gois; Ferreira, André Teixeira da Silva; Pinho, Márcia de Berredo Moreira; Rosa, Patricia Sammarco; Ribeiro, Marli Rambaldi; Freire, Monica Di Calafiori; Hacker, Mariana Andrea; Nery, José Augusto da Costa; Pessolani, Maria Cristina Vidal; Tovar, Ana Maria Freire; Sarno, Euzenir Nunes; Perales, Jonas; Bozza, Fernando Augusto; Esquenazi, Danuza; Monteiro, Robson Queiroz; Lara, Flavio Alves

    2018-03-01

    Leprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae infection. In 2016, more than 200,000 new cases of leprosy were detected around the world, representing the most frequent cause of infectious irreversible deformities and disabilities. In the present work, we demonstrate a consistent procoagulant profile on 40 reactional and non-reactional multibacillary leprosy patients. A retrospective analysis in search of signs of coagulation abnormalities among 638 leprosy patients identified 35 leprosy patients (5.48%) which displayed a characteristic lipid-like clot formed between blood clot and serum during serum harvesting, herein named 'leprosum clot'. Most of these patients (n = 16, 45.7%) belonged to the lepromatous leprosy pole of the disease. In addition, formation of the leprosum clot was directly correlated with increased plasma levels of soluble tissue factor and von Willebrand factor. High performance thin layer chromatography demonstrated a high content of neutral lipids in the leprosum clot, and proteomic analysis demonstrated that the leprosum clot presented in these patients is highly enriched in fibrin. Remarkably, differential 2D-proteomics analysis between leprosum clots and control clots identified two proteins present only in leprosy patients clots: complement component 3 and 4 and inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP). In agreement with those observations we demonstrated that M. leprae induces hepatocytes release of IHRP in vitro. We demonstrated that leprosy MB patients develop a procoagulant status due to high levels of plasmatic fibrinogen, anti-cardiolipin antibodies, von Willebrand factor and soluble tissue factor. We propose that some of these components, fibrinogen for example, presents potential as predictive biomarkers of leprosy reactions, generating tools for earlier diagnosis and treatment of these events.

  1. Does whole blood coagulation analysis reflect developmental haemostasis?

    DEFF Research Database (Denmark)

    Ravn, Hanne Berg; Andreasen, Jo Bønding; Hvas, Anne-Mette

    2017-01-01

    .05), but there was no sign of developmental changes in whole blood coagulation assessment when applying ROTEM, apart from clotting time in the EXTEM assay (P reach statistical significance. Citrate-anticoagulated blood showed...

  2. Coagulation competence and fluid recruitment after moderate blood loss in young men

    DEFF Research Database (Denmark)

    Zaar, Morten; Mørkeberg, Jakob; Pott, Frank C

    2014-01-01

    The coagulation system is activated by a reduction of the central blood volume during orthostatic stress and lower body negative pressure suggesting that also a blood loss enhances coagulation. During bleeding, however, the central blood volume is supported by fluid recruitment to the circulation...

  3. A new protein inhibitor of trypsin and activated Hageman factor from pumpkin (Cucurbita maxima) seeds.

    Science.gov (United States)

    Krishnamoorthi, R; Gong, Y X; Richardson, M

    1990-10-29

    A protein inhibitor (CMTI-V; Mr 7106) of trypsin and activated Hageman factor (Factor XIIa), a serine protease involved in blood coagulation, has been isolated for the first time from pumpkin (Cucurbita maxima) seeds by means of trypsin-affinity chromatography and reverse phase high performance liquid chromatography (HPLC). The dissociation constants of the inhibitor complexes with trypsin and Factor XIIa have been determined to be 1.6 x 10(-8) and 4.1 x 10(-8) M, respectively. The primary structure of CMTI-V is reported. The protein has 68 amino acid residues and one disulfide bridge and shows a high level of sequence homology to the Potato I inhibitor family. Furthermore, its amino terminus consists of an N-acetylates Ser. The reactive site has been established to be the peptide bond between Lys44-Asp45. The modified inhibitor which has the reactive site peptide bond hydrolyzed inhibits trypsin but not the Hageman factor.

  4. Inhibitory Effect of Triterpenoids from Panax ginseng on Coagulation Factor X

    Directory of Open Access Journals (Sweden)

    Lingxin Xiong

    2017-04-01

    Full Text Available Enzymes involved in the coagulation process have received great attention as potential targets for the development of oral anti-coagulants. Among these enzymes, coagulation factor Xa (FXa has remained the center of attention in the last decade. In this study, 16 ginsenosides and two sapogenins were isolated, identified and quantified. To determine the inhibitory potential on FXa, the chromogenic substrates method was used. The assay suggested that compounds 5, 13 and 18 were mainly responsible for the anti-coagulant effect. Furthermore, these three compounds also possessed high thrombin selectivity in the thrombin inhibition assay. Furthermore, Glide XP from Schrödinger was employed for molecular docking to clarify the interaction between the bioactive compounds and FXa. Therefore, the chemical and biological results indicate that compounds 5 (ginsenoside Rg2, 13 (ginsenoside Rg3 and 18 (protopanaxtriol, PPT are potential natural inhibitors against FXa.

  5. Risk of disseminated intravascular coagulation in patients undergoing US-guided transperineal prostatic biopsy

    International Nuclear Information System (INIS)

    Stella, M.S.; Comparato, D.; Camici, M.; Evangelisti, L.; Gaudio, V.; De Negri, F.; Talarico, L.; Giusti, C.; Morelli, G.

    1991-01-01

    Disseminated intravascular coagulation (DIC) is a severe life-threatening acute bleeding disorder. Traumatized tissues, tumors, necrotic tissues, or bacterial endotoxines release similar material in the blood to the tissutal factors activating the coagulation cascade. This preliminary study was aimed at verifying the risk of DIV in patients undergoing US-guided transperineal prostatic biopsy with Chiba and Tru-Cut needles. To evaluate the activation degree of coagulation factors in the circulation, the authors measured the concentrations of urinary fibrin degradation products in 10 patients undergoing US-guided transperineal prostatic biopsy, both before and after biopsy, every second hour, for 24 hours. Every tube of urine sample contained soya bean trypsin inhibitor and bovine thrombin to prevent any further fibrin degradation during incubation period for the possible presence of blood in urine samples. The results showed that 7/10 patients had marked increase in urinary fibrin degradation product levels (up to 800 XXXX%), with a 3-phase trend: early peak after 2-6 hours, middle peak after 6-14 hours, and late peak after 18-24 hours, which proved the activation of the coagulation cascade

  6. Moojenactivase, a novel pro-coagulant PIIId metalloprotease isolated from Bothrops moojeni snake venom, activates coagulation factors II and X and induces tissue factor up-regulation in leukocytes.

    Science.gov (United States)

    Sartim, Marco A; Costa, Tassia R; Laure, Helen J; Espíndola, Milena S; Frantz, Fabiani G; Sorgi, Carlos A; Cintra, Adélia C O; Arantes, Eliane C; Faccioli, Lucia H; Rosa, José C; Sampaio, Suely V

    2016-05-01

    Coagulopathies following snakebite are triggered by pro-coagulant venom toxins, in which metalloproteases play a major role in envenomation-induced coagulation disorders by acting on coagulation cascade, platelet function and fibrinolysis. Considering this relevance, here we describe the isolation and biochemical characterization of moojenactivase (MooA), a metalloprotease from Bothrops moojeni snake venom, and investigate its involvement in hemostasis in vitro. MooA is a glycoprotein of 85,746.22 Da, member of the PIIId group of snake venom metalloproteases, composed of three linked disulfide-bonded chains: an N-glycosylated heavy chain, and two light chains. The venom protease induced human plasma clotting in vitro by activating on both blood coagulation factors II (prothrombin) and X, which in turn generated α-thrombin and factor Xa, respectively. Additionally, MooA induced expression of tissue factor (TF) on the membrane surface of peripheral blood mononuclear cells (PBMC), which led these cells to adopt pro-coagulant characteristics. MooA was also shown to be involved with production of the inflammatory mediators TNF-α, IL-8 and MCP-1, suggesting an association between MooA pro-inflammatory stimulation of PBMC and TF up-regulation. We also observed aggregation of washed platelets when in presence of MooA; however, the protease had no effect on fibrinolysis. Our findings show that MooA is a novel hemostatically active metalloprotease, which may lead to the development of coagulopathies during B. moojeni envenomation. Moreover, the metalloprotease may contribute to the development of new diagnostic tools and pharmacological approaches applied to hemostatic disorders.

  7. Photoacoustic discrimination of viable and thermally coagulated blood using a two-wavelength method for burn injury monitoring

    International Nuclear Information System (INIS)

    Talbert, Robert J; Holan, Scott H; Viator, John A

    2007-01-01

    Discriminating viable from thermally coagulated blood in a burn wound can be used to profile burn depth, thus aiding the removal of necrotic tissue. In this study, we used a two-wavelength photoacoustic imaging method to discriminate coagulated and non-coagulated blood in a dermal burn phantom. Differences in the optical absorption spectra of coagulated and non-coagulated blood produce different values of the ratio of peak photoacoustic amplitude at 543 and 633 nm. The absorption values obtained from spectroscopic measurements indicate that the ratio of photoacoustic pressure for 543 and 633 nm for non-coagulated blood was 15.7:1 and 1.6:1 for coagulated blood. Using planar blood layers, we found the photoacoustic ratios to be 13.5:1 and 1.6:1, respectively. Using the differences in the ratios of coagulated and non-coagulated blood, we propose a scheme using statistical classification analysis to identify the different blood samples. Based upon these distinctly different ratios, we identified the planar blood samples with an error rate of 0%. Using a burn phantom with cylindrical vessels containing coagulated and non-coagulated blood, we achieved an error rate of 11.4%. These results have shown that photoacoustic imaging could prove to be a valuable tool in the diagnosis of burns

  8. Blood coagulation abnormalities in multibacillary leprosy patients.

    Directory of Open Access Journals (Sweden)

    Débora Santos da Silva

    2018-03-01

    Full Text Available Leprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae infection. In 2016, more than 200,000 new cases of leprosy were detected around the world, representing the most frequent cause of infectious irreversible deformities and disabilities.In the present work, we demonstrate a consistent procoagulant profile on 40 reactional and non-reactional multibacillary leprosy patients. A retrospective analysis in search of signs of coagulation abnormalities among 638 leprosy patients identified 35 leprosy patients (5.48% which displayed a characteristic lipid-like clot formed between blood clot and serum during serum harvesting, herein named 'leprosum clot'. Most of these patients (n = 16, 45.7% belonged to the lepromatous leprosy pole of the disease. In addition, formation of the leprosum clot was directly correlated with increased plasma levels of soluble tissue factor and von Willebrand factor. High performance thin layer chromatography demonstrated a high content of neutral lipids in the leprosum clot, and proteomic analysis demonstrated that the leprosum clot presented in these patients is highly enriched in fibrin. Remarkably, differential 2D-proteomics analysis between leprosum clots and control clots identified two proteins present only in leprosy patients clots: complement component 3 and 4 and inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP. In agreement with those observations we demonstrated that M. leprae induces hepatocytes release of IHRP in vitro.We demonstrated that leprosy MB patients develop a procoagulant status due to high levels of plasmatic fibrinogen, anti-cardiolipin antibodies, von Willebrand factor and soluble tissue factor. We propose that some of these components, fibrinogen for example, presents potential as predictive biomarkers of leprosy reactions, generating tools for earlier diagnosis and treatment of these events.

  9. The genetic variation rs6903956 in the novel androgen-dependent tissue factor pathway inhibitor regulating protein (ADTRP) gene is not associated with levels of plasma coagulation factors in the Singaporean Chinese

    OpenAIRE

    Chang, Xuling; Chin, Hui-Lin; Quek, Swee-Chye; Goh, Daniel Y. T.; Dorajoo, Rajkumar; Friedlander, Yechiel; Heng, Chew-Kiat

    2017-01-01

    Background Genome-wide association study (GWAS) has reported that rs6903956 within the first intron of androgen-dependent tissue factor pathway inhibitor (TFPI) regulating protein (ADTRP) gene is associated with coronary artery disease (CAD) risk in the Chinese population. Although ADTRP is believed to be involved in the upregulation of TFPI, the underlying mechanism involved is largely unknown. This study investigated the association of rs6903956 with plasma Factor VII coagulant activity (FV...

  10. The effects of nanomaterials on blood coagulation in hemostasis and thrombosis.

    Science.gov (United States)

    Simak, Jan; De Paoli, Silvia

    2017-09-01

    The blood coagulation balance in the organism is achieved by the interaction of the blood platelets (PLTs) with the plasma coagulation system (PCS) and the vascular endothelial cells. In healthy organism, these systems prevent thrombosis and, in events of vascular damage, enable blood clotting to stop bleeding. The dysregulation of hemostasis may cause serious thrombotic and/or hemorrhagic pathologies. Numerous engineered nanomaterials are being investigated for biomedical purposes and are unavoidably exposed to the blood. Also, nanomaterials may access vascular system after occupational, environmental, or other types of exposure. Thus, it is essential to evaluate the effects of engineered nanomaterials on hemostasis. This review focuses on investigations of nanomaterial interactions with the blood components involved in blood coagulation: the PCS and PLTs. Particular emphases include the pathophysiology of effects of nanomaterials on the PCS, including the kallikrein-kinin system, and on PLTs. Methods for investigating these interactions are briefly described, and a review of the most important studies on the interactions of nanomaterials with plasma coagulation and platelets is provided. WIREs Nanomed Nanobiotechnol 2017, 9:e1448. doi: 10.1002/wnan.1448 For further resources related to this article, please visit the WIREs website. © Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  11. Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

    Science.gov (United States)

    Cronin, Katherine R; Mangan, Thomas P; Carew, Josephine A

    2012-01-01

    Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, pfactor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.

  12. Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

    Directory of Open Access Journals (Sweden)

    Katherine R Cronin

    Full Text Available BACKGROUND: Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. METHODOLOGY/PRINCIPAL FINDINGS: Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, p<0.001 at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. CONCLUSIONS/SIGNIFICANCE: Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.

  13. Effect of Continuous Positive Airway Pressure Ventilation on Platelet-activating Factor and Blood Coagulation Function in Patients with Obstructive Sleep Apnea-hypopnea Syndrome

    International Nuclear Information System (INIS)

    Chen Xiangkun; Sheng Chunyong

    2010-01-01

    To investigate the effect of continuous positive airway pressure ventilation (CPAP) on platelet-activating factor (PAF) expression and blood coagulation function in patients with obstructive sleep apnea-hypopnea syndrome (OSAS), the blood sample of 40 patients with OSAS were taken before treatment and on the day 30 after treatment respectively. PAF, thromboxane B 2 (TXB2), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrin(FIB) in patients and 37 health controls were detected. The results showed that PAF, TXB2, FIB in OSAS patients before treatment were significantly higher than those of after treatment and control group (P 0.05). There were abnormal expression of PAF and hypercoagulability in OSAS patients. CPAP could effectively decrease the expression of PAF, TXB 2 and could also correct dysfunction of blood coagulation. It had certain effect in lightening the clinical symptoms in OSAS patients. (authors)

  14. The M358R variant of α_1-proteinase inhibitor inhibits coagulation factor VIIa

    International Nuclear Information System (INIS)

    Sheffield, William P.; Bhakta, Varsha

    2016-01-01

    The naturally occurring M358R mutation of the plasma serpin α_1-proteinase inhibitor (API) changes both its cleavable reactive centre bond to Arg–Ser and the efficacy with which it inhibits different proteases, reducing the rate of inhibition of neutrophil elastase, and enhancing that of thrombin, factor XIa, and kallikrein, by several orders of magnitude. Although another plasma serpin with an Arg–Ser reactive centre, antithrombin (AT), has been shown to inhibit factor VIIa (FVIIa), no published data are available with respect to FVIIa inhibition by API M358R. Recombinant bacterially-expressed API M358R and plasma-derived AT were therefore compared using gel-based and kinetic assays of FVIIa integrity and activity. Under pseudo-first order conditions of excess serpin over protease, both AT and API M358R formed denaturation-resistant inhibitory complexes with FVIIa in reactions accelerated by TF; AT, but not API M358R, also required heparin for maximal activity. The second order rate constant for heparin-independent API M358R-mediated FVIIa inhibition was determined to be 7.8 ± 0.8 × 10"2 M"−"1sec"−"1. We conclude that API M358R inhibits FVIIa by forming inhibitory complexes of the serpin type more rapidly than AT in the absence of heparin. The likely 20-fold excess of API M358R over AT in patient plasma during inflammation raises the possibility that it could contribute to the hemorrhagic tendencies manifested by rare individuals expressing this mutant serpin. - Highlights: • The inhibitory specificity of the serpin alpha-1-proteinase inhibitor (API) is sharply altered in the M358R variant. • API M358R forms denaturation-resistant complexes with coagulation factor VIIa at a rate accelerated by tissue factor but unaffected by heparin. • Complex formation was shown by gel-based assays and quantified kinetically by inhibition of FVIIa-dependent amidolysis.

  15. Bloodcurdling movies and measures of coagulation: Fear Factor crossover trial.

    Science.gov (United States)

    Nemeth, Banne; Scheres, Luuk J J; Lijfering, Willem M; Rosendaal, Frits R

    2015-12-16

    To assess whether, as has been hypothesised since medieval times, acute fear can curdle blood. Crossover trial. Main meeting room of Leiden University's Department of Clinical Epidemiology, the Netherlands, converted to a makeshift cinema. 24 healthy volunteers aged ≤30 years recruited among students, alumni, and employees of the Leiden University Medical Center: 14 were assigned to watch a frightening (horror) movie followed by a non-threatening (educational) movie and 10 to watch the movies in reverse order. The movies were viewed more than a week apart at the same time of day and both lasted approximately 90 minutes. The primary outcome measures were markers, or "fear factors" of coagulation activity: blood coagulant factor VIII, D-dimer, thrombin-antithrombin complexes, and prothrombin fragments 1+2. The secondary outcome was participant reported fear experienced during each movie using a visual analogue fear scale. All participants completed the study. The horror movie was perceived to be more frightening than the educational movie on a visual analogue fear scale (mean difference 5.4, 95% confidence interval 4.7 to 6.1). The difference in factor VIII levels before and after watching the movies was higher for the horror movie than for the educational movie (mean difference of differences 11.1 IU/dL (111 IU/L), 95% confidence interval 1.2 to 21.0 IU/dL). The effect of either movie on levels of thrombin-antithrombin complexes, D-dimer, and prothrombin fragments 1+2 did not differ. Frightening (in this case, horror) movies are associated with an increase of blood coagulant factor VIII without actual thrombin formation in young and healthy adults. Trial registration ClinicalTrials.gov NCT02601053. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Real-time electrical impedimetric monitoring of blood coagulation process under temperature and hematocrit variations conducted in a microfluidic chip.

    Directory of Open Access Journals (Sweden)

    Kin Fong Lei

    Full Text Available Blood coagulation is an extremely complicated and dynamic physiological process. Monitoring of blood coagulation is essential to predict the risk of hemorrhage and thrombosis during cardiac surgical procedures. In this study, a high throughput microfluidic chip has been developed for the investigation of the blood coagulation process under temperature and hematocrit variations. Electrical impedance of the whole blood was continuously recorded by on-chip electrodes in contact with the blood sample during coagulation. Analysis of the impedance change of the blood was conducted to investigate the characteristics of blood coagulation process and the starting time of blood coagulation was defined. The study of blood coagulation time under temperature and hematocrit variations was shown a good agreement with results in the previous clinical reports. The electrical impedance measurement for the definition of blood coagulation process provides a fast and easy measurement technique. The microfluidic chip was shown to be a sensitive and promising device for monitoring blood coagulation process even in a variety of conditions. It is found valuable for the development of point-of-care coagulation testing devices that utilizes whole blood sample in microliter quantity.

  17. Trp[superscript 2313]-His[superscript 2315] of Factor VIII C2 Domain Is Involved in Membrane Binding Structure of a Complex Between the C[subscript 2] Domain and an Inhibitor of Membrane Binding

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhuo; Lin, Lin; Yuan, Cai; Nicolaes, Gerry A.F.; Chen, Liqing; Meehan, Edward J.; Furie, Bruce; Furie, Barbara; Huang, Mingdong (Harvard-Med); (UAH); (Maastricht); (Chinese Aca. Sci.)

    2010-11-03

    Factor VIII (FVIII) plays a critical role in blood coagulation by forming the tenase complex with factor IXa and calcium ions on a membrane surface containing negatively charged phospholipids. The tenase complex activates factor X during blood coagulation. The carboxyl-terminal C2 domain of FVIII is the main membrane-binding and von Willebrand factor-binding region of the protein. Mutations of FVIII cause hemophilia A, whereas elevation of FVIII activity is a risk factor for thromboembolic diseases. The C2 domain-membrane interaction has been proposed as a target of intervention for regulation of blood coagulation. A number of molecules that interrupt FVIII or factor V (FV) binding to cell membranes have been identified through high throughput screening or structure-based design. We report crystal structures of the FVIII C2 domain under three new crystallization conditions, and a high resolution (1.15 {angstrom}) crystal structure of the FVIII C2 domain bound to a small molecular inhibitor. The latter structure shows that the inhibitor binds to the surface of an exposed {beta}-strand of the C2 domain, Trp{sup 2313}-His{sup 2315}. This result indicates that the Trp{sup 2313}-His{sup 2315} segment is an important constituent of the membrane-binding motif and provides a model to understand the molecular mechanism of the C2 domain membrane interaction.

  18. Influence of ionizing radiation and 12-crown-4 on coagulation system components of rat blood

    International Nuclear Information System (INIS)

    Kratenko, R.Yi.

    2006-01-01

    The influence of 12-crown-4 and ionizing radiation on some components of blood coagulation system: Ca 2+ contents and prostaglandin concentrations in the blood serum, and erythrocyte contents in the blood plasma are studied. The influence of 12-crown-4 and ionizing radiation increases the coagulational properties of erythrocytes. The synergism of ionizing irradiation and 12-crown-4 influence blood coagulation process points out at the occurrence of radiomimetic properties of the latter

  19. Optical coherence tomography-guided laser microsurgery for blood coagulation with continuous-wave laser diode.

    Science.gov (United States)

    Chang, Feng-Yu; Tsai, Meng-Tsan; Wang, Zu-Yi; Chi, Chun-Kai; Lee, Cheng-Kuang; Yang, Chih-Hsun; Chan, Ming-Che; Lee, Ya-Ju

    2015-11-16

    Blood coagulation is the clotting and subsequent dissolution of the clot following repair to the damaged tissue. However, inducing blood coagulation is difficult for some patients with homeostasis dysfunction or during surgery. In this study, we proposed a method to develop an integrated system that combines optical coherence tomography (OCT) and laser microsurgery for blood coagulation. Also, an algorithm for positioning of the treatment location from OCT images was developed. With OCT scanning, 2D/3D OCT images and angiography of tissue can be obtained simultaneously, enabling to noninvasively reconstruct the morphological and microvascular structures for real-time monitoring of changes in biological tissues during laser microsurgery. Instead of high-cost pulsed lasers, continuous-wave laser diodes (CW-LDs) with the central wavelengths of 450 nm and 532 nm are used for blood coagulation, corresponding to higher absorption coefficients of oxyhemoglobin and deoxyhemoglobin. Experimental results showed that the location of laser exposure can be accurately controlled with the proposed approach of imaging-based feedback positioning. Moreover, blood coagulation can be efficiently induced by CW-LDs and the coagulation process can be monitored in real-time with OCT. This technology enables to potentially provide accurate positioning for laser microsurgery and control the laser exposure to avoid extra damage by real-time OCT imaging.

  20. Development of Coagulation Factor Probes for the Identification of Procoagulant Circulating Tumor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Tormoen, Garth W.; Cianchetti, Flor A. [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR (United States); Bock, Paul E. [Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN (United States); McCarty, Owen J. T., E-mail: tormoeng@ohsu.edu [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR (United States); Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR (United States); Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health and Science University, Portland, OR (United States)

    2012-09-06

    Metastatic cancer is associated with a hypercoagulable state, and pathological venous thromboembolic disease is a significant source of morbidity and the second leading cause of death in patients with cancer. Here we aimed to develop a novel labeling strategy to detect and quantify procoagulant circulating tumor cells (CTCs) from patients with metastatic cancer. We hypothesize that the enumeration of procoagulant CTCs may be prognostic for the development of venous thrombosis in patients with cancer. Our approach is based on the observation that cancer cells are capable of initiating and facilitating cell-mediated coagulation in vitro, whereby activated coagulation factor complexes assemble upon cancer cell membrane surfaces. Binding of fluorescently labeled, active site-inhibited coagulation factors VIIa, Xa, and IIa to the metastatic breast cancer cell line, MDA-MB-231, non-metastatic colorectal cell line, SW480, or metastatic colorectal cell line, SW620, was characterized in a purified system, in anticoagulated blood and plasma, and in plasma under conditions of coagulation. We conclude that a CTC labeling strategy that utilizes coagulation factor-based fluorescent probes may provide a functional assessment of the procoagulant potential of CTCs, and that this strategy is amenable to current CTC detection platforms.

  1. The M358R variant of α{sub 1}-proteinase inhibitor inhibits coagulation factor VIIa

    Energy Technology Data Exchange (ETDEWEB)

    Sheffield, William P., E-mail: sheffiel@mcmaster.ca [Canadian Blood Services, Centre for Innovation, Hamilton, Ontario (Canada); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario (Canada); Bhakta, Varsha [Canadian Blood Services, Centre for Innovation, Hamilton, Ontario (Canada)

    2016-02-12

    The naturally occurring M358R mutation of the plasma serpin α{sub 1}-proteinase inhibitor (API) changes both its cleavable reactive centre bond to Arg–Ser and the efficacy with which it inhibits different proteases, reducing the rate of inhibition of neutrophil elastase, and enhancing that of thrombin, factor XIa, and kallikrein, by several orders of magnitude. Although another plasma serpin with an Arg–Ser reactive centre, antithrombin (AT), has been shown to inhibit factor VIIa (FVIIa), no published data are available with respect to FVIIa inhibition by API M358R. Recombinant bacterially-expressed API M358R and plasma-derived AT were therefore compared using gel-based and kinetic assays of FVIIa integrity and activity. Under pseudo-first order conditions of excess serpin over protease, both AT and API M358R formed denaturation-resistant inhibitory complexes with FVIIa in reactions accelerated by TF; AT, but not API M358R, also required heparin for maximal activity. The second order rate constant for heparin-independent API M358R-mediated FVIIa inhibition was determined to be 7.8 ± 0.8 × 10{sup 2} M{sup −1}sec{sup −1}. We conclude that API M358R inhibits FVIIa by forming inhibitory complexes of the serpin type more rapidly than AT in the absence of heparin. The likely 20-fold excess of API M358R over AT in patient plasma during inflammation raises the possibility that it could contribute to the hemorrhagic tendencies manifested by rare individuals expressing this mutant serpin. - Highlights: • The inhibitory specificity of the serpin alpha-1-proteinase inhibitor (API) is sharply altered in the M358R variant. • API M358R forms denaturation-resistant complexes with coagulation factor VIIa at a rate accelerated by tissue factor but unaffected by heparin. • Complex formation was shown by gel-based assays and quantified kinetically by inhibition of FVIIa-dependent amidolysis.

  2. Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells.

    Science.gov (United States)

    Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

    2009-12-15

    Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.

  3. Early markers of blood coagulation and fibrinolysis activation in Argentine hemorrhagic fever

    NARCIS (Netherlands)

    Heller, M. V.; Marta, R. F.; Sturk, A.; Maiztegui, J. I.; Hack, C. E.; Cate, J. W.; Molinas, F. C.

    1995-01-01

    Junin virus, an arenaviridae, is the etiological agent of Argentine hemorrhagic fever. In addition to thrombocytopenia, patients present several alterations in both the blood coagulation and the fibrinolytic system, but diffuse intravascular coagulation could not be demonstrated. To investigate

  4. Contemporary developments in the discovery of selective factor Xa inhibitors: A review.

    Science.gov (United States)

    Patel, Nirav R; Patel, Dushyant V; Murumkar, Prashant R; Yadav, Mange Ram

    2016-10-04

    Thrombosis is a leading cause of death in cardiovascular diseases such as myocardial infarction (MI), unstable angina and acute coronary syndrome (ACS) in the industrialized world. Venous thromboembolism is observed in about 1 million people every year in United States causing significant morbidity and mortality. Conventional antithrombotic therapy has been reported to have several disadvantages and limitations like inconvenience in oral administration, bleeding risks (heparin analogs), narrow therapeutic window and undesirable interactions with food and drugs (vitamin K antagonist-warfarin). The unmet medical demand for orally active safe anticoagulants has generated widespread interest among the medicinal chemists engaged in this field. To modulate blood coagulation, various enzymes involved in the coagulation process have received great attention as potential targets by various research groups for the development of oral anticoagulants. Among these enzymes, factor Xa (FXa) has remained the centre of attention in the last decade. Intensive research efforts have been made by various research groups for the development of small, safe and orally bioavailable FXa inhibitors. This review is an attempt to compile the research work of various researchers in the direction of development of FXa inhibitors reported since 2010 onward. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Caveats in studies of the physiological role of polyphosphates in coagulation.

    Science.gov (United States)

    Lindahl, Tomas L; Ramström, Sofia; Boknäs, Niklas; Faxälv, Lars

    2016-02-01

    Platelet-derived polyphosphates (polyP), stored in dense granule and released upon platelet activation, have been claimed to enhance thrombin activation of coagulation factor XI (FXI) and to activate FXII directly. The latter claim is controversial and principal results leading to these conclusions are probably influenced by methodological problems. It is important to consider that low-grade contact activation is initiated by all surfaces and is greatly amplified by the presence of phospholipids simulating the procoagulant membranes of activated platelets. Thus, proper use of inhibitors of the contact pathway and a careful choice of materials for plates and tubes is important to avoid artefacts. The use of phosphatases used to degrade polyP has an important drawback as it also degrades the secondary activators ADP and ATP, which are released from activated platelets. In addition, the use of positively charged inhibitors, such as polymyxin B, to inhibit polyP in platelet-rich plasma and blood is problematic, as polymyxin B also slows coagulation in the absence of polyP. In conclusion we hope awareness of the above caveats may improve research on the physiological roles of polyP in coagulation. © 2016 Authors; published by Portland Press Limited.

  6. Effect of flomoxef on blood coagulation and alcohol metabolism.

    Science.gov (United States)

    Uchida, K; Matsubara, T

    1991-01-01

    The effect of flomoxef, a newly developed oxacephem antibiotic with an N-hydroxyethyltetrazolethiol (HTT) side chain, on blood coagulation and alcohol metabolism was compared with that of a series of cephalosporin antibiotics with N-methyltetrazolethiol (NMTT), thiadiazolethiol (TDT) or methylthiadiazolethiol (MTDT) side chains in position 3' of the cephalosporin nucleus known to cause hypoprothrombinemia and bleeding in patients who are malnourished, debilitated and/or of high age. A disulfiram-like effect caused by inhibition of aldehyde dehydrogenase was observed for NMTT-containing antibiotics. Studies were carried out on healthy volunteers and on rats. Eight-day treatment with 2 g flomoxef i.v. once or twice daily in five and six healthy male volunteers, respectively, did not cause any significant changes in prothrombin time (PT), coagulation factors II, VII, IX or X, in hepaplastin values or fibrinogen levels, activated partial thromboplastin time (APTT), platelet counts, bleeding time, or collagen- and ADP-induced platelet aggregation. Inhibition of vitamin K epoxide reductase was observed in rats treated with flomoxef, yet to a much lesser extent than observed for cephalosporins with NMTT, TDT or MTDT side chains. This defect was quickly normalized by vitamin K injection. There were no differences between oxacephem (1-O) and cephem (1-S) compounds with respect to effects on blood clotting and platelet aggregation. Flomoxef and its side chain HTT showed no influence on alcohol metbolism.

  7. Anti-Factor V inhibitor in patients with autoimmune diseases: case report and literature review

    Directory of Open Access Journals (Sweden)

    Imashuku S

    2011-04-01

    Full Text Available Shinsaku Imashuku1, Takeshi Hasegawa2, Kagekatsu Kubo2, Masaki Nakato2, Midori Shima31Division of Pediatrics and Hematology, 2Division of Internal Medicine, Takasago-Seibu Hospital, Takasago, Hyogo; 3Department of Pediatrics, Nara Medical University, Kashihara, Nara, JapanAbstract: Acquired anti-Factor V deficiency caused by inhibitor production is a rare coagulation disorder. Although this is a well known entity in the literature, choice of optimal treatment for an individual patient is difficult, given that no standard therapeutic measures are available because of rare incidence and various underlying diseases occurring in the elderly. An 88 year-old man treated for Hashimoto's disease was found to exhibit prolongation of both prothrombin time and activated partial thromboplastin time. Detailed study of coagulation factors revealed a deficiency of Factor V. Our patient's coagulation disorder resolved in two weeks with intravenous administration of prednisolone 20 mg/day. Clinical features of autoimmune disease-related Factor V deficiency are discussed, along with eight previously reported cases over the past 20 years.Keywords: anti-Factor V inhibitor, Hashimoto's thyroiditis, autoimmune disease

  8. Measurement of blood coagulation with considering RBC aggregation through a microchip-based light transmission aggregometer.

    Science.gov (United States)

    Lim, Hyunjung; Nam, Jeonghun; Xue, Shubin; Shin, Sehyun

    2011-01-01

    Even though blood coagulation can be tested by various methods and techniques, the effect of RBC aggregation on blood coagulation is not fully understood. The present study monitored clot formation in a microchip-based light transmission aggregometer. Citrated blood samples with and without the addition of calcium ion solution were initially disaggregated by rotating a stirrer in the microchip. After abrupt stop of the rotating stirrer, the transmitted light intensity over time was recorded. The syllectogram (light intensity vs. time graph) manifested a rapid increase that is associated with RBC aggregation followed by a decrease that is associated with blood coagulation. The time to reach the peak point was used as a new index of coagulation time (CT) and ranged from 200 to 500 seconds in the present measurements. The CT was inversely proportional to the concentration of fibrinogen, which enhances RBC aggregation. In addition, the CT was inversely proportional to the hematocrit, which is similar to the case of the prothrombin time (PT), as measured by a commercial coagulometer. Thus, we carefully concluded that RBC aggregation should be considered in tests of blood coagulation.

  9. [Factor XIII-guided treatment algorithm reduces blood transfusion in burn surgery].

    Science.gov (United States)

    Carneiro, João Miguel Gonçalves Valadares de Morais; Alves, Joana; Conde, Patrícia; Xambre, Fátima; Almeida, Emanuel; Marques, Céline; Luís, Mariana; Godinho, Ana Maria Mano Garção; Fernandez-Llimos, Fernando

    Major burn surgery causes large hemorrhage and coagulation dysfunction. Treatment algorithms guided by ROTEM ® and factor VIIa reduce the need for blood products, but there is no evidence regarding factor XIII. Factor XIII deficiency changes clot stability and decreases wound healing. This study evaluates the efficacy and safety of factor XIII correction and its repercussion on transfusion requirements in burn surgery. Randomized retrospective study with 40 patients undergoing surgery at the Burn Unit, allocated into Group A those with factor XIII assessment (n = 20), and Group B, those without assessment (n = 20). Erythrocyte transfusion was guided by a hemoglobin trigger of 10g.dL -1 and the other blood products by routine coagulation and ROTEM ® tests. Analysis of blood product consumption included units of erythrocytes, fresh frozen plasma, platelets, and fibrinogen. The coagulation biomarker analysis compared the pre- and post-operative values. Group A (with factor XIII study) and Group B had identical total body surface area burned. All patients in Group A had a preoperative factor XIII deficiency, whose correction significantly reduced units of erythrocyte concentrate transfusion (1.95 vs. 4.05, p = 0.001). Pre- and post-operative coagulation biomarkers were similar between groups, revealing that routine coagulation tests did not identify factor XIII deficiency. There were no recorded thromboembolic events. Correction of factor XIII deficiency in burn surgery proved to be safe and effective for reducing perioperative transfusion of erythrocyte units. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  10. Blood coagulation and fibrinolysis of the whole-body irradiated rabbits

    International Nuclear Information System (INIS)

    Hishikawa-Itoh, Youko; Ayakawa, Yoshio; Miyata, Nobuki

    1984-01-01

    To study the effects of irradiation on blood coagulation and fibrinolysis, rabbits were irradiated with 60 Co γ-rays (whole-body: 0, 100, 400, 800, 1200 rads). Clotting time, activity of plasmin and plasminogen, and fibrinogen contents of irradiated rabbit plasma were measured at 4 days before, immediately after, and at 1, 3, 7, 10, and 14 days after irradiation. Both clotting times obtained by addition of (kaolin+phospholipid) which expressed effects on the total intrinsic coagulation system, and by addition of (Ca 2+ ) which expressed effects on the total extrinsic coagulation system, were prolonged with small dose irradiation (100 rads) immediately and 3 days after irradiation. However, with high dose irradiation (400-1200 rads), these clotting times were prolonged 1 day after irradiation. The times of manifestation of irradiation effects on clotting time were different in small and high dose irradiation. Plasmin activity was decreased immediately, 1 day after and recovered 3 days after irradiation. Plasminogen activity was markedly increased in 800 and 1200 rads irradiated groups from 3 days after irradiation. Conversion of plasminogen into plasmin was impaired by irradiation. Fibrinogen contents increased rapidly in all irradiated rabbits except for 100 rads from 1 day after irradiation. These results revealed decreased coagulation and fibrinolysis activities in rabbit blood, irradiation injury of both coagulation and fibrinolysis activation systems, and accumulation of the precursors of fibrin and plasmin (i.e., fibrinogen and plasminogen). (author)

  11. In-traffic air pollution exposure and CC16, blood coagulation, and inflammation markers in healthy adults.

    Science.gov (United States)

    Zuurbier, Moniek; Hoek, Gerard; Oldenwening, Marieke; Meliefste, Kees; Krop, Esmeralda; van den Hazel, Peter; Brunekreef, Bert

    2011-10-01

    Exposure to traffic-related air pollution is a risk factor for cardiovascular events, probably involving mechanisms of inflammation and coagulation. Little is known about effects of the short exposures encountered while participating in traffic. The objective of the study was to examine effects of exposure of commuters to air pollution on cardiovascular biomarkers. Thirty-four healthy adult volunteers commuted for 2 hr by bus, car, or bicycle during the morning rush hour. During the commute, exposure to particle number, particulate matter (PM) ≤ 2.5 µm in aerodynamic diameter (PM2.5), PM ≤ 10 µm in diameter (PM10), and soot was measured. We estimated inhaled doses based on heart rate monitoring. Shortly before exposure and 6 hr after exposure, blood samples were taken and analyzed for CC16 (Clara cell protein 16), blood cell count, coagulation markers, and inflammation markers. Between June 2007 and June 2008, 352 pre- and postexposure blood samples were collected on 47 test days. We used mixed models to analyze the associations between exposure and changes in health parameters. We observed no consistent associations between the air pollution exposures and doses and the various biomarkers that we investigated. Air pollution exposure during commuting was not consistently associated with acute changes in inflammation markers, blood cell counts, or blood coagulation markers.

  12. Quality control in the development of coagulation factor concentrates.

    Science.gov (United States)

    Snape, T J

    1987-01-01

    Limitation of process change is a major factor contributing to assurance of quality in pharmaceutical manufacturing. This is particularly true in the manufacture of coagulation factor concentrates, for which presumptive testing for poorly defined product characteristics is an integral feature of finished product quality control. The development of new or modified preparations requires that this comfortable position be abandoned, and that the effect on finished product characteristics of changes to individual process steps (and components) be assessed. The degree of confidence in the safety and efficacy of the new product will be determined by, amongst other things, the complexity of the process alteration and the extent to which the results of finished product tests can be considered predictive. The introduction of a heat-treatment step for inactivation of potential viral contaminants in coagulation factor concentrates presents a significant challenge in both respects, quite independent of any consideration of assessment of the effectiveness of the viral inactivation step. These interactions are illustrated by some of the problems encountered with terminal dry heat-treatment (72 h. at 80 degrees C) of factor VIII and prothrombin complex concentrates manufactured by the Blood Products Laboratory.

  13. Coagulation defects in experimental hepatic injury in the dog.

    Science.gov (United States)

    Osbaldiston, G W; Hoffman, M W

    1971-04-01

    Alteration in activity of blood coagulation factors in dogs with acute hepatic injury caused by oral carbon tetrachloride dosing was studied. Coagulation Factors II, VII and IX were dramatically reduced within 48 hours but recovered to normal in the next five days. Because surgery is rarely performed on dogs with hepatic necrosis, the use of fresh whole blood tranfusion to improve the coagulation defect in hepatic injury was also studied. Transfusion was found to have only a temporary beneficial effect.

  14. Blood coagulation parameters and activity indices in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    A. A. Arshinov

    2005-01-01

    Full Text Available Objective. To assess coagulation parameters and activity indices in pts with systemic lupus erythematosus (SLE. Material and methods . 86 pts with SLE (83 female and 3 male were examined. 12 of them had antiphospholipid syndrome. Mean age was 35,9±1,5 years (from 18 to 58 years, mean disease duration was 9,8+1,4 years. Control group consisted of 60 healthy volunteers with mean age 37,1+4,1 years. SLE activity assessment was performed with SLAM, SLEDAI and ECLAM indices. Results. SLE pts showed 5-fold (p<0,01 increase of spontaneous platelets aggregation and more than 3-fold increase of factor von Willebrand antigen (FWA concentration. Platelet activation in pts was accompanied by decrease of platelet aggregation with collagen (on 27%, p<0,01. Characteristic sign of coagulation hemostasis activation was significant increase of soluble fibrin-monomer complexes (SFMC concentration on 81 % (p<0,01 so as increase D-dimers level in 53,3% of pts. Fibrinogen concentration was increased on 29%, spontaneous fibrinolysis parameters were decreased on 20%, antithrombin (AT 111 - on 21% in comparison with control. Direct correlation between activity indiccs and SFMC(ECLAM, r=0,5, fibrinogen concentration (SLAM, r=0,34, D- dimers level (ECLAM, r=0,5, spontaneous platelet aggregation (ECLAM, r=0,5 so as inverse correlation with AT III activity (SLEDAI, r-0,73 was revealed. Conclusion. Changes of hemostasis parameters in SLE may serve as predictors of thrombotic disorders development and indication to drug correction of blood coagulation disorders. Direct correlation between blood coagulation system activity and indices of SLE activity.

  15. Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia.

    Science.gov (United States)

    Tatsumi, Kohei; Ohashi, Kazuo; Taminishi, Sanae; Takagi, Soichi; Utoh, Rie; Yoshioka, Akira; Shima, Midori; Okano, Teruo

    2009-11-14

    To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia (DH)-mediated liver regeneration. Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a representative hepatomitogen. Mice were weighed and sacrificed at various time points [Day 0 (D0: prior to injection), 3 h, D1, D2, D3, and D10] after TCPOBOP administration to obtain liver and blood samples. Using the RNA samples extracted from the liver, a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, protein S, ADAMTS13, and VWF). The corresponding plasma levels of coagulation factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, X, XI, XII, XIII, and VWF) were also analyzed and compared with their mRNA levels. Gavage administration of TCPOBOP (3 mg/kg body weight) resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the D0 (control) ratios. At the peak of liver regeneration (D1 and D2), the gene expression levels for most of the coagulation-related factors (fibrinogen, prothrombin, factors V, VII, VIII, IX, XI, XII, XIIIbeta, plasminogen, antithrombin, protein C, ADAMTS13, VWF) were found to be down-regulated in a time-dependent manner, and gradually recovered by D10 to the basal levels. Only mRNA levels of factor X and protein S failed to show any decrease during the regenerative phase. As for the plasma levels, 5 clotting factors (prothrombin, factors VIII, IX, XI, and XII) demonstrated a significant decrease (Pfactors, factor IX and factor XI showed the most dramatic decline in their activities by about 50% at D2 compared to the basal levels, and these reductions in

  16. Influences of ABO blood group, age and gender on plasma coagulation factor VIII, fibrinogen, von Willebrand factor and ADAMTS13 levels in a Chinese population.

    Science.gov (United States)

    Wang, Zongkui; Dou, Miaomiao; Du, Xi; Ma, Li; Sun, Pan; Cao, Haijun; Ye, Shengliang; Jiang, Peng; Liu, Fengjuan; Lin, Fangzhao; Zhang, Rong; Li, Changqing

    2017-01-01

    ABO blood group is a hereditary factor of plasma levels of coagulation factor VIII (FVIII) and von Willebrand factor (VWF). Age and gender have been shown to influence FVIII, VWF, fibrinogen (Fbg), and ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 motif, 13). We investigated the effects of ABO type, age, and gender on plasma levels of FVIII, Fbg, VWF, and ADAMTS13 in a Chinese population. A total of 290 healthy volunteers were eligible for this study. ABO blood group was determined by indirect technique. FVIII:C and Fbg were measured by clotting assays. VWF antigen (VWF:Ag), collagen-binding activity (VWF:CBA), and ADAMTS13 antigen were assessed by ELISA, whereas VWF ristocetin cofactor activity (VWF:Rcof) was performed by agglutination of platelets with ristocetin. Mean FVIII:C and VWF levels (VWF:Ag, VWF:CBA, and VWF:Rcof) were significantly higher in non-O than in O type subjects ( p  blood group, age, and gender showed different effects on plasma levels of FVIII:C, Fbg, VWF:Ag, VWF:CBA, VWF:Rcof, and ADAMTS13 antigen. These new data on a Chinese population are quite helpful to compare with other ethnic groups.

  17. Whole blood coagulation time, haematocrit, haemoglobin and total ...

    African Journals Online (AJOL)

    The study was carried out to determine the values of whole blood coagulation time (WBCT), haematocrit (HM), haemaglobin (HB) and total protein (TP) of one hundred and eighteen apparently healthy turkeys reared under an extensive management system in Zaria. The mean values for WBCT, HM, HB and TP were 1.12 ...

  18. Interaction of blood coagulation factor Va with phospholipid vesicles examined by using lipophilic photoreagents

    International Nuclear Information System (INIS)

    Krieg, U.C.; Isaacs, B.S.; Yemul, S.S.; Esmon, C.T.; Bayley, H.; Johnson, A.E.

    1987-01-01

    Two different lipophilic photoreagents, [ 3 H]adamantane diazirine and 3-(trifluoromethyl)-3-(m-[ 125 I]iodophenyl)diazirine (TID), have been utilized to examine the interactions of blood coagulation factor Va with calcium, prothrombin, factor Xa, and, in particular, phospholipid vesicles. With each of these structurally dissimilar reagents, the extent of photolabeling of factor Va was greater when the protein was bound to a membrane surface than when it was free in solution. Specifically, the covalent photoreaction with Vl, the smaller subunit of factor Va, was 2-fold higher in the presence of phosphatidylcholine/phosphatidylserine (PC/PS, 3:1) vesicles, to which factor Va binds, than in the presence of 100% PC vesicles, to which the protein does not bind. However, the magnitude of the PC/PS-dependent photolabeling was much less than has been observed previously with integral membrane proteins. It therefore appears that the binding of factor Va to the membrane surface exposes Vl to the lipid core of the bilayer, but that only a small portion of the Vl polypeptide is exposed to, or embedded in, the bilayer core. Addition of either prothrombin or active-site-blocked factor Xa to PC/PS-bound factor Va had little effect on the photolabeling of Vl with TID, but reduced substantially the covalent labeling of Vh, the larger subunit of factor Va. This indicates that prothrombin and factor Xa each cover nonpolar surfaces on Vh when the macromolecules associate on the PC/PS surface. It therefore seems likely that the formation of the prothrombinase complex involves a direct interaction between Vh and factor Xa and between Vh and prothrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Purification and Autoactivation Method for Recombinant Coagulation Factor VII.

    Science.gov (United States)

    Granovski, Vladimir; Freitas, Marcela C C; Abreu-Neto, Mario Soares; Covas, Dimas T

    2018-01-01

    Recombinant coagulation factor VII is a very important and complex protein employed for treatment of hemophiliac patients (hemophilia A/B) who develop inhibitors antibodies to conventional treatments (FVIII and FIX). The rFVII is a glycosylated molecule and circulates in plasma as zymogen of 50 kDa. When activated the molecule is cleaved to 20-30 kDa and has a half-life of about 3 h, needing to be processed fast and efficiently until freeze-drying. Here, we describe a very simple and fast purification sequence for rFVII using affinity FVII Select resin and a dialysis system that can be easily scaled up.

  20. Blood Coagulation and Acid-Base Balance at Craniocerebral Hypothermia in Patients with Severe Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    V. E. Avakov

    2015-01-01

    Full Text Available Systemic therapeutic hypothermia has gained a negative reputation in treating multiple trauma patients and is regarded as one of the factors in the lethal triad of shock, acidosis, and hypothermia. This fact owes to no relationship between acidosis and hypothermia; the effects of the latter on coagulation are evident and complexly reversible in the presence of acidosis.Objective: to determine the impact of noninvasive local brain cooling on the metabolic and blood coagulation indicators of a patient with acute cerebral ischemia.Subjects and methods. The subjects of the study were 113 patients with severe brain injury, including that complicated by the involvement of stem structures, who underwent brain cooling in different modifications. In so doing, the val ues of acidbase balance and coagulation system in arterial and venous blood were investigated.Results. Local brain hypother mia was not found to affect coagulation while the baseline negative values of excess buffer bases showed positive values (a right shift by the end of cooling. Recommendations were given to prevent metabolic shifts.Conclusion. Patients at very high risk for bleeding may be safely cooled to a brain temperature of 32—34°C even in the presence of moderatetosevere acidosis. This is a great advantage of local hypothermia over systemic one.

  1. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

    Science.gov (United States)

    Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

    2016-06-23

    The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

  2. Theories of blood coagulation.

    Science.gov (United States)

    Riddel, James P; Aouizerat, Bradley E; Miaskowski, Christine; Lillicrap, David P

    2007-01-01

    Although the concept of the coagulation cascade represented a significant advance in the understanding of coagulation and served for many years as a useful model, more recent clinical and experimental observations demonstrate that the cascade/waterfall hypothesis does not fully and completely reflect the events of hemostasis in vivo. The goal of this article is to review the evolution of the theories of coagulation and their proposed models to serve as a tool when reviewing the research and practice literature that was published in the context of these different theories over time.

  3. Anomalous coagulation factors in non-arteritic anterior ischemic optic neuropathy with central retinal vein occlusion: A case report.

    Science.gov (United States)

    Kim, Ji Hong; Kang, Min Ho; Seong, Mincheol; Cho, Heeyoon; Shin, Yong Un

    2018-04-01

    Non-arteritic anterior ischemic optic neuropathy (NAION) is characterized by sudden, painless visual loss and optic disc edema. NAION occurs mainly in the presence of cardiovascular disease and hypercoagulability, mainly in patients over 50 years of age. We experienced a case of NAION associated with central retinal vein occlusion (CRVO) in a young man with no underlying disease. A 46-year-old man was referred to our clinic following a sudden loss of vision in his right eye. The patient exhibited no underlying disease and reported no ongoing medication. Significant visual loss and visual disturbance of the right eye were observed. The pupil of the right eye was enlarged and an afferent pupillary defect was observed. On fundus examination, retinal hemorrhage was observed in the peripheral retina; macular edema was observed in optical coherence tomography analysis. However, optic disc edema was not evident. No abnormal findings were found in routine blood tests for hypercoagulability. After 3 days of steroid intravenous injection, macular edema disappeared and visual acuity was improved, but optic disc edema began to appear. One week later, optic disc edema was evident and visual acuity was significantly reduced; thus, the patient was diagnosed with NAION. In fluorescein angiography, peripheral retinal ischemia was observed, suggesting that CRVO was complicated. Blood tests, including analysis of coagulation factors, were performed again, showing that coagulation factors IX and XI were increased. Anomalous coagulation factors in non-arteritic anterior ischemic optic neuropathy with central retinal vein occlusion. Systemic steroids were administered. One month later, optic disc edema and retinal hemorrhage gradually diminished and eventually disappeared; however, visual acuity did not recover. In young patients without underlying disease, cases of NAION require careful screening for coagulation disorders. Even if there is no abnormality in the test for routine

  4. Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time.

    Science.gov (United States)

    Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

    2015-12-01

    Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs) = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2) and melittin, and that can increase the blood clotting times in vitro.

  5. Honey Bee Venom (Apis mellifera Contains Anticoagulation Factors and Increases the Blood-clotting Time

    Directory of Open Access Journals (Sweden)

    Hossein Zolfagharian

    2015-12-01

    Full Text Available Objectives: Bee venom (BV is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50, and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. Blood samples were obtained from 10 rabbits, and the prothrombin time (PT and the partial thromboplastin time (PTT tests were conducted. The approximate lethal dose (LD values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa, respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2 and melittin, and that can increase the blood clotting times in vitro.

  6. Review Blood coagulation factor VIII

    Indian Academy of Sciences (India)

    Unknown

    the development of inhibitors in patients with hemophilia A. 2. Lifespan. 2.1 FVIII gene .... intron 22 inversion is principally an error of DNA repli- cation during ..... Pittman D D, Wang J H and Kaufman R J 1992 Identification and functional ...

  7. Blood coagulation in lead poisoning and the influence of specific treatment

    Energy Technology Data Exchange (ETDEWEB)

    Levantovskaya, O M; Lyubcenko, P N; Dayhin, I S; Sorkina, N S

    1974-07-01

    Results of blood coagulation studies in 104 workers with long-term exposure in a storage-battery plant. Over-all coagulation activity is unchanged in cases of mild lead poisoning, but long-term exposure gives rise to increased fibrinogen levels, activated fibrinolysis, and reduced serum accelerator globulin and prothrombin activities. 13 workers were given D-penicillamine (oral doses of 450 mg daily). All coagulation indices had become normal after 10 days' treatment. The changes observed are thought to be due to protein synthesis disturbances in the liver and to inhibition of enzymes by lead which combines with their sulfhydryl and disulfide groups. (CIS Abstr. Vol. 2)

  8. Perioperative coagulation management and blood conservation in cardiac surgery: a Canadian Survey.

    Science.gov (United States)

    Taneja, Ravi; Fernandes, Philip; Marwaha, Gulshan; Cheng, Davy; Bainbridge, Daniel

    2008-10-01

    To determine which strategies are currently used for (anti)coagulation management and blood conservation during cardiac surgery in Canada. Institutional survey. University hospital. All sites performing cardiac surgery in Canada. None. The response rate was 85%. Anticoagulation with heparin is monitored routinely through the activated coagulation time (ACT). Less than 10% of centers use heparin concentrations (Hepcon HMS, Medtronic), thromboelastography, or other point-of-care tests perioperatively. Eighty percent of centers routinely use tranexamic acid as the primary antifibrinolytic agent; however aprotinin until recently, was used more commonly for patients at increased risk for bleeding. Retrograde autologous prime is commonly used (62%); however, cell savers are uncommon for routine patients undergoing cardiac surgery (29%). Although most hospitals use a hematocrit of 20% to 21% for transfusing red blood cells, more than 50% of intensive care units do not have written guidelines for the administration of protamine, fresh frozen plasma, platelets, or factor VIIa. At least one third of centers do not audit their transfusion practices regularly. The majority of Canadian institutions do not use point-of-care tests other than ACT. Most institutions do not have algorithms for management of bleeding following cardiac surgery and at least 30% do not monitor their transfusion practice perioperatively. Cardiac surgery patients in Canada may benefit from a standardized approach to blood conservation in the perioperative period.

  9. Hydroxyethyl Starch Reduces Coagulation Competence and Increases Blood Loss During Major Surgery

    DEFF Research Database (Denmark)

    Rasmussen, Kirsten C; Johansson, Pär I; Højskov, Michael

    2014-01-01

    OBJECTIVE: This study evaluated whether administration of hydroxyethyl starch (HES) 130/0.4 affects coagulation competence and influences the perioperative blood loss. BACKGROUND: Artificial colloids substitute blood volume during surgery; with the administration of HES 130/0.4 (Voluven, Fresenius...

  10. Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells

    Science.gov (United States)

    Göbel, Kerstin; Pankratz, Susann; Asaridou, Chloi-Magdalini; Herrmann, Alexander M.; Bittner, Stefan; Merker, Monika; Ruck, Tobias; Glumm, Sarah; Langhauser, Friederike; Kraft, Peter; Krug, Thorsten F.; Breuer, Johanna; Herold, Martin; Gross, Catharina C.; Beckmann, Denise; Korb-Pap, Adelheid; Schuhmann, Michael K.; Kuerten, Stefanie; Mitroulis, Ioannis; Ruppert, Clemens; Nolte, Marc W.; Panousis, Con; Klotz, Luisa; Kehrel, Beate; Korn, Thomas; Langer, Harald F.; Pap, Thomas; Nieswandt, Bernhard; Wiendl, Heinz; Chavakis, Triantafyllos; Kleinschnitz, Christoph; Meuth, Sven G.

    2016-01-01

    Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. PMID:27188843

  11. Characterization of coagulation factor synthesis in nine human primary cell types

    NARCIS (Netherlands)

    Dashty, Monireh; Akbarkhanzadeh, Vishtaseb; Zeebregts, Clark J.; Spek, C. Arnold; Sijbrands, Eric J.; Peppelenbosch, Maikel P.; Rezaee, Farhad

    2012-01-01

    The coagulation/fibrinolysis system is essential for wound healing after vascular injury. According to the standard paradigm, the synthesis of most coagulation factors is restricted to liver, platelets and endothelium. We challenged this interpretation by measuring coagulation factors in nine human

  12. Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders

    Directory of Open Access Journals (Sweden)

    Pär I Johansson

    2010-06-01

    Full Text Available Pär I Johansson, Sisse R OstrowskiCapital Region Blood Bank, Section for Transfusion Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkBackground: Recombinant activated factor VII (rFVIIa, NovoSeven® was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX.Objective: To review the evidence supporting the use of rFVIIa for the treatment of patients with congenital bleeding disorders.Patients and methods: English-language databases were searched in September 2009 for reports of randomized controlled trials (RCTs evaluating the ability of rFVIIa to restore hemostasis in patients with congenital bleeding disorders.Results: Eight RCTs involving 256 hemophilic patients with antibodies against coagulation factors, also known as inhibitors, were identified. The evidence supporting the use of rFVIIa in these patients was weak with regard to dose, clinical setting, mode of administration, efficacy, and adverse events, given the limited sample size of each RCT and the heterogeneity of the studies.Conclusion: The authors suggest that rFVIIa therapy in hemophilic patients with inhibitors should be based on the individual’s ability to generate thrombin and form a clot, and not on the patient’s weight alone. Therefore, assays for thrombin generation, such as whole-blood thromboelastography, have the potential to significantly improve the treatment of these patients.Keywords: hemophilia, inhibitors, coagulation factor VIII, coagulation factor IX, rFVIIa, NovoSeven, FEIBA, hemostasis, RCT

  13. Networks of enzymatically oxidized membrane lipids support calcium-dependent coagulation factor binding to maintain hemostasis

    NARCIS (Netherlands)

    Lauder, S.N.; Allen-Redpath, K.; Slatter, D.A.; Aldrovandi, M.; O'Connor, A.; Farewell, D.; Percy, C.L.; Molhoek, J.E.; Rannikko, S.; Tyrrell, V.J.; Ferla, S.; Milne, G.L.; Poole, A.W.; Thomas, C.P.; Obaji, S.; Taylor, P.R.; Jones, S.A.; Groot, P.G. de; Urbanus, R.T.; Horkko, S.; Uderhardt, S.; Ackermann, J.; Jenkins, P.V.; Brancale, A.; Kronke, G.; Collins, P.W.; O'Donnell, V.B.

    2017-01-01

    Blood coagulation functions as part of the innate immune system by preventing bacterial invasion, and it is critical to stopping blood loss (hemostasis). Coagulation involves the external membrane surface of activated platelets and leukocytes. Using lipidomic, genetic, biochemical, and mathematical

  14. Air quality improvement during 2010 Asian games on blood coagulability in COPD patients.

    Science.gov (United States)

    Zhang, Zili; Wang, Jian; Guo, Meihua; Xiong, Mingmei; Zhou, Qipeng; Li, Defu; Shu, Jiaze; Lu, Wenju; Sun, Dejun

    2016-04-01

    Exposure to elevated levels of ambient air pollutants can lead to adverse cardiovascular effects. Perturbation of the coagulation balance is one of the potential mechanisms. However, evidence regarding the impact of improvement in air pollution on blood coagulability in COPD patients has never been reported. Coagulation processes are known to be of relevance for cardiovascular pathology; therefore, this study aimed to investigate the association of short-term air pollution exposure with blood marker (D-dimer) of coagulation. A 3-year (through the Asian game) cohort study based on the GIRD COPD Biobank Project was conducted in 36 COPD patients to estimate whether changes in measurements of D-dimer were associated with changes in pollutant concentration, comparing for 51 intervention days (November 1-December 21) in 2010 with the same calendar date of baseline years (2009 and 2011). Daily mean concentrations of air pollutants and meteorological variables were measured during the time. Daily PM10 decreased from 65.86 μg/m(3) during the baseline period to 62.63 μg/m(3) during the Asian Games period; daily NO2 decreased from 51.33 to 42.63 μg/m(3). SO2 and other weather variables did not differ substantially. We did not observe statistically significant improvements in D-dimer levels by 9.86% from a pre-Asian game mean of 917 ng/ml to a during-Asian game mean of 1007 ng/ml, platelet number by 11.66%, PH by -0.15%, PCO2 by -6.54%, and PO2 by -1.16%. In the post-Asian game period, when pollutant concentrations increased, most outcomes approximated pre-Asian game levels, and similar effects were also demonstrated in D-dimer, platelet number, and arterial blood gas. For D-dimer and platelet number, we observed statistically significant increases associated with increases in NO2 at lag 1-3 and SO2 at lag 2-4. For PH, PCO2, and PO2, any significant effect was not demonstrated. This study gives no support to the hypothesis that reduction in air pollution levels during the

  15. In Vitro impairment of whole blood coagulation and platelet function by hypertonic saline hydroxyethyl starch

    Directory of Open Access Journals (Sweden)

    Görlinger Klaus

    2011-02-01

    Full Text Available Abstract Background Hypertonic saline hydroxyethyl starch (HH has been recommended for first line treatment of hemorrhagic shock. Its effects on coagulation are unclear. We studied in vitro effects of HH dilution on whole blood coagulation and platelet function. Furthermore 7.2% hypertonic saline, 6% hydroxyethylstarch (as ingredients of HH, and 0.9% saline solution (as control were tested in comparable dilutions to estimate specific component effects of HH on coagulation. Methods The study was designed as experimental non-randomized comparative in vitro study. Following institutional review board approval and informed consent blood samples were taken from 10 healthy volunteers and diluted in vitro with either HH (HyperHaes®, Fresenius Kabi, Germany, hypertonic saline (HT, 7.2% NaCl, hydroxyethylstarch (HS, HAES6%, Fresenius Kabi, Germany or NaCl 0.9% (ISO in a proportion of 5%, 10%, 20% and 40%. Coagulation was studied in whole blood by rotation thrombelastometry (ROTEM after thromboplastin activation without (ExTEM and with inhibition of thrombocyte function by cytochalasin D (FibTEM, the latter was performed to determine fibrin polymerisation alone. Values are expressed as maximal clot firmness (MCF, [mm] and clotting time (CT, [s]. Platelet aggregation was determined by impedance aggregrometry (Multiplate after activation with thrombin receptor-activating peptide 6 (TRAP and quantified by the area under the aggregation curve (AUC [aggregation units (AU/min]. Scanning electron microscopy was performed to evaluate HyperHaes induced cell shape changes of thrombocytes. Statistics: 2-way ANOVA for repeated measurements, Bonferroni post hoc test, p Results Dilution impaired whole blood coagulation and thrombocyte aggregation in all dilutions in a dose dependent fashion. In contrast to dilution with ISO and HS, respectively, dilution with HH as well as HT almost abolished coagulation (MCFExTEM from 57.3 ± 4.9 mm (native to 1.7 ± 2.2 mm (HH 40

  16. Lowering blood glucose during hip surgery does not influence coagulation activation

    Directory of Open Access Journals (Sweden)

    Marjolein K. Sechterberger

    2015-06-01

    Conclusion: Although the human GLP-1 analogue liraglutide moderately reduced post-operative blood glucose levels in non-diabetic and prediabetic obese patients undergoing elective hip surgery, no changes were observed with respect to coagulation activation.

  17. The feed gas composition determines the degree of physical plasma-induced platelet activation for blood coagulation

    Science.gov (United States)

    Bekeschus, Sander; Brüggemeier, Janik; Hackbarth, Christine; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Partecke, Lars-Ivo; van der Linde, Julia

    2018-03-01

    Cold atmospheric (physical) plasma has long been suggested to be a useful tool for blood coagulation. However, the clinical applicability of this approach has not been addressed sufficiently. We have previously demonstrated the ability of a clinically accepted atmospheric pressure argon plasma jet (kINPen® MED) to coagulate liver incisions in mice with similar performance compared to the gold standard electrocauterization. We could show that plasma-mediated blood coagulation was dependent on platelet activation. In the present work, we extended on this by investigating kINPen®-mediated platelet activation in anticoagulated human donor blood ex vivo. With focus on establishing high-throughput, multi-parametric platelet activation assays and performing argon feed gas parameter studies we achieved the following results: (i) plasma activated platelets in heparinized but not in EDTA-anticoagulated blood; (ii) plasma decreased total platelet counts but increased numbers of microparticles; (iii) plasma elevated the expression of several surface activation markers on platelets (CD62P, CD63, CD69, and CD41/61); (iv) in platelet activation, wet and dry argon plasma outperformed feed gas admixtures with oxygen and/or nitrogen; (v) plasma-mediated platelet activation was accompanied by platelet aggregation. Platelet aggregation is a necessary requirement for blood clot formation. These findings are important to further elucidate molecular details and clinical feasibility of cold physical plasma-mediated blood coagulation.

  18. Numerical simulations of a reduced model for blood coagulation

    Science.gov (United States)

    Pavlova, Jevgenija; Fasano, Antonio; Sequeira, Adélia

    2016-04-01

    In this work, the three-dimensional numerical resolution of a complex mathematical model for the blood coagulation process is presented. The model was illustrated in Fasano et al. (Clin Hemorheol Microcirc 51:1-14, 2012), Pavlova et al. (Theor Biol 380:367-379, 2015). It incorporates the action of the biochemical and cellular components of blood as well as the effects of the flow. The model is characterized by a reduction in the biochemical network and considers the impact of the blood slip at the vessel wall. Numerical results showing the capacity of the model to predict different perturbations in the hemostatic system are discussed.

  19. coagulation factors level in fresh frozen plasma in rwanda

    African Journals Online (AJOL)

    2014-02-02

    Feb 2, 2014 ... Setting: Jomo Kenyatta University of Agriculture and Technology in ... a major role in blood coagulation process. ... storage conditions and quality control prior to clinical ... instrumentation Laboratory Company USA made in.

  20. Overview of the coagulation system.

    Science.gov (United States)

    Palta, Sanjeev; Saroa, Richa; Palta, Anshu

    2014-09-01

    Coagulation is a dynamic process and the understanding of the blood coagulation system has evolved over the recent years in anaesthetic practice. Although the traditional classification of the coagulation system into extrinsic and intrinsic pathway is still valid, the newer insights into coagulation provide more authentic description of the same. Normal coagulation pathway represents a balance between the pro coagulant pathway that is responsible for clot formation and the mechanisms that inhibit the same beyond the injury site. Imbalance of the coagulation system may occur in the perioperative period or during critical illness, which may be secondary to numerous factors leading to a tendency of either thrombosis or bleeding. A systematic search of literature on PubMed with MeSH terms 'coagulation system, haemostasis and anaesthesia revealed twenty eight related clinical trials and review articles in last 10 years. Since the balance of the coagulation system may tilt towards bleeding and thrombosis in many situations, it is mandatory for the clinicians to understand physiologic basis of haemostasis in order to diagnose and manage the abnormalities of the coagulation process and to interpret the diagnostic tests done for the same.

  1. Overview of the coagulation system

    Directory of Open Access Journals (Sweden)

    Sanjeev Palta

    2014-01-01

    Full Text Available Coagulation is a dynamic process and the understanding of the blood coagulation system has evolved over the recent years in anaesthetic practice. Although the traditional classification of the coagulation system into extrinsic and intrinsic pathway is still valid, the newer insights into coagulation provide more authentic description of the same. Normal coagulation pathway represents a balance between the pro coagulant pathway that is responsible for clot formation and the mechanisms that inhibit the same beyond the injury site. Imbalance of the coagulation system may occur in the perioperative period or during critical illness, which may be secondary to numerous factors leading to a tendency of either thrombosis or bleeding. A systematic search of literature on PubMed with MeSH terms ′coagulation system, haemostasis and anaesthesia revealed twenty eight related clinical trials and review articles in last 10 years. Since the balance of the coagulation system may tilt towards bleeding and thrombosis in many situations, it is mandatory for the clinicians to understand physiologic basis of haemostasis in order to diagnose and manage the abnormalities of the coagulation process and to interpret the diagnostic tests done for the same.

  2. Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector.

    Science.gov (United States)

    Herzog, R W; Yang, E Y; Couto, L B; Hagstrom, J N; Elwell, D; Fields, P A; Burton, M; Bellinger, D A; Read, M S; Brinkhous, K M; Podsakoff, G M; Nichols, T C; Kurtzman, G J; High, K A

    1999-01-01

    Hemophilia B is a severe X-linked bleeding diathesis caused by the absence of functional blood coagulation factor IX, and is an excellent candidate for treatment of a genetic disease by gene therapy. Using an adeno-associated viral vector, we demonstrate sustained expression (>17 months) of factor IX in a large-animal model at levels that would have a therapeutic effect in humans (up to 70 ng/ml, adequate to achieve phenotypic correction, in an animal injected with 8.5x10(12) vector particles/kg). The five hemophilia B dogs treated showed stable, vector dose-dependent partial correction of the whole blood clotting time and, at higher doses, of the activated partial thromboplastin time. In contrast to other viral gene delivery systems, this minimally invasive procedure, consisting of a series of percutaneous intramuscular injections at a single timepoint, was not associated with local or systemic toxicity. Efficient gene transfer to muscle was shown by immunofluorescence staining and DNA analysis of biopsied tissue. Immune responses against factor IX were either absent or transient. These data provide strong support for the feasibility of the approach for therapy of human subjects.

  3. UPLC-MRM Mass Spectrometry Method for Measurement of the Coagulation Inhibitors Dabigatran and Rivaroxaban in Human Plasma and Its Comparison with Functional Assays.

    Directory of Open Access Journals (Sweden)

    Joachim Kuhn

    Full Text Available The fast, precise, and accurate measurement of the new generation of oral anticoagulants such as dabigatran and rivaroxaban in patients' plasma my provide important information in different clinical circumstances such as in the case of suspicion of overdose, when patients switch from existing oral anticoagulant, in patients with hepatic or renal impairment, by concomitant use of interaction drugs, or to assess anticoagulant concentration in patients' blood before major surgery.Here, we describe a quick and precise method to measure the coagulation inhibitors dabigatran and rivaroxaban using ultra-performance liquid chromatography electrospray ionization-tandem mass spectrometry in multiple reactions monitoring (MRM mode (UPLC-MRM MS. Internal standards (ISs were added to the sample and after protein precipitation; the sample was separated on a reverse phase column. After ionization of the analytes the ions were detected using electrospray ionization-tandem mass spectrometry. Run time was 2.5 minutes per injection. Ion suppression was characterized by means of post-column infusion.The calibration curves of dabigatran and rivaroxaban were linear over the working range between 0.8 and 800 μg/L (r >0.99. Limits of detection (LOD in the plasma matrix were 0.21 μg/L for dabigatran and 0.34 μg/L for rivaroxaban, and lower limits of quantification (LLOQ in the plasma matrix were 0.46 μg/L for dabigatran and 0.54 μg/L for rivaroxaban. The intraassay coefficients of variation (CVs for dabigatran and rivaroxaban were < 4% and 6%; respectively, the interassay CVs were < 6% for dabigatran and < 9% for rivaroxaban. Inaccuracy was < 5% for both substances. The mean recovery was 104.5% (range 83.8-113.0% for dabigatran and 87.0% (range 73.6-105.4% for rivaroxaban. No significant ion suppressions were detected at the elution times of dabigatran or rivaroxaban. Both coagulation inhibitors were stable in citrate plasma at -20°C, 4°C and even at RT for at

  4. Coagulation factor VII variants resistant to inhibitory antibodies.

    Science.gov (United States)

    Branchini, Alessio; Baroni, Marcello; Pfeiffer, Caroline; Batorova, Angelika; Giansily-Blaizot, Muriel; Schved, Jean F; Mariani, Guglielmo; Bernardi, Francesco; Pinotti, Mirko

    2014-11-01

    Replacement therapy is currently used to prevent and treat bleeding episodes in coagulation factor deficiencies. However, structural differences between the endogenous and therapeutic proteins might increase the risk for immune complications. This study was aimed at identifying factor (F)VII variants resistant to inhibitory antibodies developed after treatment with recombinant activated factor VII (rFVIIa) in a FVII-deficient patient homozygous for the p.A354V-p.P464Hfs mutation, which predicts trace levels of an elongated FVII variant in plasma. We performed fluorescent bead-based binding, ELISA-based competition as well as fluorogenic functional (activated FX and thrombin generation) assays in plasma and with recombinant proteins. We found that antibodies displayed higher affinity for the active than for the zymogen FVII (half-maximal binding at 0.54 ± 0.04 and 0.78 ± 0.07 BU/ml, respectively), and inhibited the coagulation initiation phase with a second-order kinetics. Isotypic analysis showed a polyclonal response with a large predominance of IgG1. We hypothesised that structural differences in the carboxyl-terminus between the inherited FVII and the therapeutic molecules contributed to the immune response. Intriguingly, a naturally-occurring, poorly secreted and 5-residue truncated FVII (FVII-462X) escaped inhibition. Among a series of truncated rFVII molecules, we identified a well-secreted and catalytically competent variant (rFVII-464X) with reduced binding to antibodies (half-maximal binding at 0.198 ± 0.003 BU/ml) as compared to the rFVII-wt (0.032 ± 0.002 BU/ml), which led to a 40-time reduced inhibition in activated FX generation assays. Taken together our results provide a paradigmatic example of mutation-related inhibitory antibodies, strongly support the FVII carboxyl-terminus as their main target and identify inhibitor-resistant FVII variants.

  5. Pulsed cold plasma-induced blood coagulation and its pilot application in stanching bleeding during rat hepatectomy

    Science.gov (United States)

    Keping, YAN; Qikang, JIN; Chao, ZHENG; Guanlei, DENG; Shengyong, YIN; Zhen, LIU

    2018-04-01

    This paper presents plasma-induced blood coagulation and its pilot application in rat hepatectomy by using a home-made pulsed cold plasma jet. Experiments were conducted on blood coagulation in vitro, the influence of plasma on tissue in vivo, and the pilot application of rat hepatectomy. Experimental results show that the cold plasma can lead to rapid blood coagulation. Compared with the control sample, the plasma-induced agglomerated layer of blood is thicker and denser, and is mostly composed of broken platelets. When the surface of the liver was treated by plasma, the influence of the plasma can penetrate into the liver to a depth of about 500 μm. During the rat hepatectomy, cold plasma was proved to be effective for stanching bleeding on incision. No obvious bleeding was found in the abdominal cavities of all six rats 48 h after the hepatectomy. This implies that cold plasma can be an effective modality to control bleeding during surgical operation.

  6. The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

    DEFF Research Database (Denmark)

    Larsen, L F; Marckmann, P; Bladbjerg, Else-Marie

    2000-01-01

    Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples...... that triglyceride-rich lipoproteins may activate prokallikrein. Neither plasma triglycerides nor kallikrein and activated FVII were statistically associated. This may suggest that additional factors are involved in the postprandial FVII activation. No clear evidence for a role of tissue factor expression...... by monocytes, factor XII or insulin in postprandial FVII activation was observed. Tissue factor pathway inhibitor and prothrombin fragment 1+2, a marker of thrombin generation, were not affected postprandially after either the high-fat or the low-fat meals. Our findings indicate that triglyceride...

  7. Anxiety and depression in patients three months after myocardial infarction: Association with markers of coagulation and the relevance of age.

    Science.gov (United States)

    Geiser, Franziska; Urbach, Anne Sarah; Harbrecht, Ursula; Conrad, Rupert; Pötzsch, Bernd; Amann, Nele; Kiesewetter, Katharina; Sieke, Alexandra; Wolffs, Kyra; Skowasch, Dirk

    2017-08-01

    Anxiety and depression are associated with an activation of coagulation and an impairment of fibrinolysis, which may contribute to the increased cardiovascular risk associated with the two disorders. However, very few studies have examined the impact of psychological distress on coagulation factors in coronary artery disease patients. The aim of this study was to assess the correlation between anxiety/depression and factors of coagulation and fibrinolysis in patients who had suffered an acute MI three months prior. In 148 patients, anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS) shortly after MI and three months later. At the second time of assessment, plasma levels of fibrinogen, factor VII, factor VIII, von Willebrand factor, prothrombin-fragment 1 and 2, tissue-plasminogen-activator, plasminogen activator inhibitor-1, D-dimer, and homocysteine were measured. In 32% of the patients, elevated levels of anxiety and depression were found three months after a MI. Multiple regression analyses showed that coagulation and fibrinolysis markers were not significantly associated with HADS anxiety and depression scores. We found that age, gender, BMI, and smoking status were significant predictors for haemostasis factors. A higher age was associated with a higher coagulability but lower anxiety levels. We measured parameters of coagulation and fibrinolysis in patients three months after MI and found no predictive value of HADS anxiety and depression scores shortly after MI or at the time of blood sampling. The effects of age on the relationship between anxiety and haemostasis should be further investigated. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Natural coagulation inhibitors and active protein c resistance in preeclampsia

    Directory of Open Access Journals (Sweden)

    Cengiz Demir

    2010-01-01

    Full Text Available INTRODUCTION: The etiology of preeclampsia is not fully established. A few studies have shown a relationship between natural coagulation inhibitors and preeclampsia. OBJECTIVES: The purpose of this study was to investigate the status of natural coagulation inhibitors and active protein C resistance (APC-R in preeclampsia. PATIENTS AND METHODS: We studied 70 women with preeclampsia recruited consecutively and 70 healthy pregnant and 70 nonpregnant women as controls. Plasma protein C (PC, free protein S (fPS, antithrombin III (ATIII and APC-R were evaluated. RESULTS: ATIII values were found to be significantly lower in preeclamptic patients than in the control groups (p< 0.001. Nevertheless, there was no significant difference between the healthy pregnant and nonpregnant women groups (p=0.141. The fPS values of the preeclamptic and healthy pregnant groups were lower than that of the nonpregnant group (p< 0.001, and the fPS value of the preeclamptic pregnant women was lower than that of healthy pregnant women (p<0.001. The PC value of the preeclamptic pregnant women was lower than that of the control groups (p< 0.001. The PC value of the healthy pregnant women was lower than that of the nonpregnant women (p< 0.001. The mean APC activity values were lower in the preeclamptic patients than that of the control groups (p< 0.001, p< 0.001. The APC-R positivity rates of the preeclamptic groups were higher than that of the control groups (p<0.001. CONCLUSIONS: This study demonstrated that ATIII, fPS, PC values and APC resistance were lower and APC-R positivity was higher in preeclamptic women than in normal pregnant and nonpregnant women.

  9. [Influence of Gentiana lutea L extract on blood coagulation].

    Science.gov (United States)

    Bakuridze, A D; Nikolaev, S M; Tsagarenshvili, N T; Kurdiani, N G; Mikaia, G A

    2009-01-01

    The dry extract from the terrestrial parts of Gentiana Lutea was received in accordance to the developed by us general technological scheme. Study of the pharmacological influence of obtained extract on the coagulating properties of blood revealed that after its per os instillation into experimental animals the time of the formation of active thromboplastin reliably increases, while the time of thrombin and fibrinous cluster formation is shortened in comparison with those indices in the animals, that did not receive phyto-preparation, at the same time morphological appearance of the peripheral blood remains unchanged. Dry extract of terrestrial parts of Gentiana Lutea prepared in accordance to the technology recommended by us, together with widely known pharmacological effects, is characterized with new activity - influence on haemostasis. Obtained preliminary data concerning influence of the extract on coagulation of the blood request further deep studies of its mechanism. Revealed new activity of the terrestrial parts of Gentiana Lutea and the studies of the mechanism of its activity will serve in future as a basis for the recommendation of its use in new nosology. Terrestrial parts of Gentiana lutea L. are proposed as an alternative of the underground parts of the plant. Alongside with that, it is expedient to continue the studies devoted to the development of the haemostatic remedies of plant origin with systemic and local action (sponges, films, skin glues) from terrestrial parts of Gentiana lutea L.

  10. Factor XI and XII as antithrombotic targets.

    Science.gov (United States)

    Müller, Felicitas; Gailani, David; Renné, Thomas

    2011-09-01

    Arterial and venous thrombosis are major causes of morbidity and mortality, and the incidence of thromboembolic diseases increases as a population ages. Thrombi are formed by activated platelets and fibrin. The latter is a product of the plasma coagulation system. Currently available anticoagulants such as heparins, vitamin K antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for terminating blood loss at sites of vascular injury. As a result, anticoagulants currently in clinical use increase the risk of bleeding, partially offsetting the benefits of reduced thrombosis. This review focuses on new targets for anticoagulation that are associated with minimal or no therapy-associated increased bleeding. Data from experimental models using mice and clinical studies of patients with hereditary deficiencies of coagulation factors XI or XII have shown that both of these clotting factors are important for thrombosis, while having minor or no apparent roles in processes that terminate blood loss (hemostasis). Hereditary deficiency of factor XII (Hageman factor) or factor XI, plasma proteases that initiate the intrinsic pathway of coagulation, impairs thrombus formation and provides protection from vascular occlusive events, while having a minimal impact on hemostasis. As the factor XII-factor XI pathway contributes to thrombus formation to a greater extent than to normal hemostasis, pharmacological inhibition of these coagulation factors may offer the exciting possibility of anticoagulation therapies with minimal or no bleeding risk.

  11. Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer.

    Science.gov (United States)

    Cui, X Y; Tinholt, M; Stavik, B; Dahm, A E A; Kanse, S; Jin, Y; Seidl, S; Sahlberg, K K; Iversen, N; Skretting, G; Sandset, P M

    2016-02-01

    ESSENTIALS: A hypoxic microenvironment is a common feature of tumors that may influence activation of coagulation. MCF-7 and SK-BR-3 breast cancer cells and breast cancer tissue samples were used. The results showed transcriptional repression of tissue factor pathway inhibitor expression in hypoxia. Hypoxia-inducible factor 1α may be a target for the therapy of cancer-related coagulation and thrombosis. Activation of coagulation is a common finding in patients with cancer, and is associated with an increased risk of venous thrombosis. As a hypoxic microenvironment is a common feature of solid tumors, we investigated the role of hypoxia in the regulation of tissue factor (TF) pathway inhibitor (TFPI) expression in breast cancer. To explore the transcriptional regulation of TFPI by hypoxia-inducible factor (HIF)-1α in breast cancer cells and their correlation in breast cancer tissues. MCF-7 and SK-BR-3 breast cancer cells were cultured in 1% oxygen or treated with cobalt chloride (CoCl2 ) to mimic hypoxia. Time-dependent and dose-dependent downregulation of TFPI mRNA (quantitative RT-PCR) and of free TFPI protein (ELISA) were observed in hypoxia. Western blotting showed parallel increases in the levels of HIF-1α protein and TF. HIF-1α inhibitor abolished or attenuated the hypoxia-induced downregulation of TFPI. Luciferase reporter assay showed that both hypoxia and HIF-1α overexpression caused strong repression of TFPI promoter activity. Subsequent chromatin immunoprecipitation and mutagenesis analysis demonstrated a functional hypoxia response element within the TFPI promoter, located at -1065 to -1060 relative to the transcriptional start point. In breast cancer tissue samples, gene expression analyses showed a positive correlation between the mRNA expression of TFPI and that of HIF-1α. This study demonstrates that HIF-1α is involved in the transcriptional regulation of the TFPI gene, and suggests that a hypoxic microenvironment inside a breast tumor may

  12. The production of coagulation factor VII by adipocytes is enhanced by tumor necrosis factor-α or isoproterenol.

    Science.gov (United States)

    Takahashi, N; Yoshizaki, T; Hiranaka, N; Kumano, O; Suzuki, T; Akanuma, M; Yui, T; Kanazawa, K; Yoshida, M; Naito, S; Fujiya, M; Kohgo, Y; Ieko, M

    2015-05-01

    A relationship has been reported between blood concentrations of coagulation factor VII (FVII) and obesity. In addition to its role in coagulation, FVII has been shown to inhibit insulin signals in adipocytes. However, the production of FVII by adipocytes remains unclear. We herein investigated the production and secretion of FVII by adipocytes, especially in relation to obesity-related conditions including adipose inflammation and sympathetic nerve activation. C57Bl/6J mice were fed a low- or high-fat diet and the expression of FVII messenger RNA (mRNA) was then examined in adipose tissue. 3T3-L1 cells were used as an adipocyte model for in vitro experiments in which these cells were treated with tumor necrosis factor-α (TNF-α) or isoproterenol. The expression and secretion of FVII were assessed by quantitative real-time PCR, Western blotting and enzyme-linked immunosorbent assays. The expression of FVII mRNA in the adipose tissue of mice fed with high-fat diet was significantly higher than that in mice fed with low-fat diet. Expression of the FVII gene and protein was induced during adipogenesis and maintained in mature adipocytes. The expression and secretion of FVII mRNA were increased in the culture medium of 3T3-L1 adipocytes treated with TNF-α, and these effects were blocked when these cells were exposed to inhibitors of mitogen-activated kinases or NF-κB activation. The β-adrenoceptor agonist isoproterenol stimulated the secretion of FVII from mature adipocytes via the cyclic AMP/protein kinase A pathway. Blockade of secreted FVII with the anti-FVII antibody did not affect the phosphorylation of Akt in the isoproterenol-stimulated adipocytes. Obese adipose tissue produced FVII. The production and secretion of FVII by adipocytes was enhanced by TNF-α or isoproterenol via different mechanisms. These results indicate that FVII is an adipokine that plays an important role in the pathogenesis of obesity.

  13. Synthesis, purification, and characterization of an Arg152 → Glu site-directed mutant of recombinant human blood clotting factor VII

    International Nuclear Information System (INIS)

    Wildgoose, P.; Kisiel, W.; Berkner, K.L.

    1990-01-01

    Coagulation factor VII circulates in blood as a single-chain zymogen of a serine protease and is converted to its activated two-chain form, factor VIIa, by cleavage of an internal peptide bond located at Arg 152 -Ile 153 . Previous studies using serine protease active-site inhibitors suggest that zymogen factor VII may possess sufficient proteolytic activity to initiate the extrinsic pathway of blood coagulation. In order to assess the putative intrinsic proteolytic activity of single-chain factor VII, the authors have constructed a site-specific mutant of recombinant human factor VII in which arginine-152 has been replaced with a glutamic acid residue. Mutant factor VII was purified in a single step from culture supernatants of baby hamster kidney cells transfected with a plasmid containing the sequence for Arg 152 → Glu factor VII using a calcium-dependent, murine anti-factor VII monoclonal antibody column. The clotting activity of mutant factor VII was completely inhibited following incubation with dansyl-Glu-Gly-Arg chloromethyl ketone, suggesting that the apparent clotting activity of mutant factor VII was due to a contaminating serine protease. Immunoblots of mutant factor VII with human factor IXa revealed no cleavage, whereas incubation of mutant factor VII with human factor Xa resulted in cleavage of mutant factor VII and the formation of a lower molecular weight degradation product migrating at M r ∼40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX

  14. Identification of anthranilamide derivatives as potential factor Xa inhibitors: drug design, synthesis and biological evaluation.

    Science.gov (United States)

    Xing, Junhao; Yang, Lingyun; Li, Hui; Li, Qing; Zhao, Leilei; Wang, Xinning; Zhang, Yuan; Zhou, Muxing; Zhou, Jinpei; Zhang, Huibin

    2015-05-05

    The coagulation enzyme factor Xa (fXa) plays a crucial role in the blood coagulation cascade. In this study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharmacophore (SBP) model and structural consensus docking were employed to identify novel fXa inhibitors. After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent high performance were identified. Then, these two hit compounds and several analogs were synthesized and screened for in-vitro inhibition of fXa. The experimental data showed that most of the designed compounds displayed significant in vitro potency against fXa. Among them, compound 9b displayed the greatest in vitro potency against fXa with the IC50 value of 23 nM and excellent selectivity versus thrombin (IC50 = 40 μM). Moreover, the prolongation of the prothrombin time (PT) was measured for compound 9b to evaluate its in vitro anticoagulant activity. As a result, compound 9b exhibited pronounced anticoagulant activity with the 2 × PT value of 8.7 μM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. Synthesis, purification, and characterization of an Arg sub 152 yields Glu site-directed mutant of recombinant human blood clotting factor VII

    Energy Technology Data Exchange (ETDEWEB)

    Wildgoose, P.; Kisiel, W. (Univ. of New Mexico, Albuquerque (USA)); Berkner, K.L. (ZymoGenetics, Inc., Seattle, WA (USA))

    1990-04-03

    Coagulation factor VII circulates in blood as a single-chain zymogen of a serine protease and is converted to its activated two-chain form, factor VIIa, by cleavage of an internal peptide bond located at Arg{sub 152}-Ile{sub 153}. Previous studies using serine protease active-site inhibitors suggest that zymogen factor VII may possess sufficient proteolytic activity to initiate the extrinsic pathway of blood coagulation. In order to assess the putative intrinsic proteolytic activity of single-chain factor VII, the authors have constructed a site-specific mutant of recombinant human factor VII in which arginine-152 has been replaced with a glutamic acid residue. Mutant factor VII was purified in a single step from culture supernatants of baby hamster kidney cells transfected with a plasmid containing the sequence for Arg{sub 152} {yields} Glu factor VII using a calcium-dependent, murine anti-factor VII monoclonal antibody column. The clotting activity of mutant factor VII was completely inhibited following incubation with dansyl-Glu-Gly-Arg chloromethyl ketone, suggesting that the apparent clotting activity of mutant factor VII was due to a contaminating serine protease. Immunoblots of mutant factor VII with human factor IXa revealed no cleavage, whereas incubation of mutant factor VII with human factor Xa resulted in cleavage of mutant factor VII and the formation of a lower molecular weight degradation product migrating at M{sup r}{approx}40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX.

  16. Predictive Value of Whole Blood and Plasma Coagulation Tests for Intra- and Postoperative Bleeding Risk: A Systematic Review

    DEFF Research Database (Denmark)

    Larsen, Julie Brogaard; Hvas, Anne-Mette

    2017-01-01

    review of the existing literature assessing the ability of whole blood coagulation (thromboelastography [TEG]/thromboelastometry [ROTEM]/Sonoclot), platelet function tests, and standard plasma-based coagulation tests to predict bleeding in the perioperative setting. We searched PubMed and Embase...... value of testing in patients receiving antithrombotic medication. In general, studies reported low positive predictive values for perioperative testing, whereas negative predictive values were high. The studies yielded moderate areas under receiver operator characteristics (ROC) curve (for the majority...... recommend that both whole blood and plasma-based coagulation tests are primarily used in case of bleeding and not for screening in unselected patients prior to surgery....

  17. Prevalence of nucleic acid sequences specific for human parvoviruses, hepatitis A and hepatitis E viruses in coagulation factor concentrates.

    Science.gov (United States)

    Modrow, S; Wenzel, J J; Schimanski, S; Schwarzbeck, J; Rothe, U; Oldenburg, J; Jilg, W; Eis-Hübinger, A M

    2011-05-01

    Due to their high resistance to inactivation procedures, nonenveloped viruses such as parvovirus B19, human bocavirus (HBoV), human parvovirus 4 (PARV4), hepatitis A (HAV) and hepatitis E virus (HEV) pose a particular threat to blood products. Virus transmission to patients treated with blood products presents an additional burden to disease. We determined the frequency and the amount of nucleic acid specific for nonenveloped viruses in recently manufactured preparations of commercial coagulation factor concentrates. At least three different batches of each of 13 different plasma-derived and recombinant coagulation factor products were tested for the presence and the amount of nucleic acid for parvovirus B19, HBoV, human parvovirus 4, hepatitis A virus and HEV by using quantitative polymerase chain reaction. Whereas none of the recombinant products tested positive for any of these viruses, parvovirus B19 DNA with amounts ranging between 2×10(1) and 1.3×10(3) genome equivalents/ml was detected in five plasma-derived products. In addition to parvovirus B19 genotype 1, genotypes 2 and 3 were observed in two batches of a factor VIII/von-Willebrand factor product. In two products (one factor VIII concentrate and one activated prothrombin complex concentrate), a combination of both genotypes 1 and 2 of parvovirus B19 was detected. The data show that nucleic acids from several relevant nonenveloped viruses are not found at detectable levels in coagulation factor concentrates. In some cases, parvovirus B19 DNA was detectable at low levels. Testing of the plasma pools for the full range of parvovirus genotypes is advocated for ensuring product safety. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

  18. Coagulation measurement from whole blood using vibrating optical fiber in a disposable cartridge.

    Science.gov (United States)

    Yaraş, Yusuf Samet; Gündüz, Ali Bars; Sağlam, Gökhan; Ölçer, Selim; Civitçi, Fehmi; Baris, İbrahim; Yaralioğlu, Göksenin; Urey, Hakan

    2017-11-01

    In clinics, blood coagulation time measurements are performed using mechanical measurements with blood plasma. Such measurements are challenging to do in a lab-on-a-chip (LoC) system using a small volume of whole blood. Existing LoC systems use indirect measurement principles employing optical or electrochemical methods. We developed an LoC system using mechanical measurements with a small volume of whole blood without requiring sample preparation. The measurement is performed in a microfluidic channel where two fibers are placed inline with a small gap in between. The first fiber operates near its mechanical resonance using remote magnetic actuation and immersed in the sample. The second fiber is a pick-up fiber acting as an optical sensor. The microfluidic channel is engineered innovatively such that the blood does not block the gap between the vibrating fiber and the pick-up fiber, resulting in high signal-to-noise ratio optical output. The control plasma test results matched well with the plasma manufacturer's datasheet. Activated-partial-thromboplastin-time tests were successfully performed also with human whole blood samples, and the method is proven to be effective. Simplicity of the cartridge design and cost of readily available materials enable a low-cost point-of-care device for blood coagulation measurements. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  19. UPLC-MRM Mass Spectrometry Method for Measurement of the Coagulation Inhibitors Dabigatran and Rivaroxaban in Human Plasma and Its Comparison with Functional Assays.

    Science.gov (United States)

    Kuhn, Joachim; Gripp, Tatjana; Flieder, Tobias; Dittrich, Marcus; Hendig, Doris; Busse, Jessica; Knabbe, Cornelius; Birschmann, Ingvild

    2015-01-01

    The fast, precise, and accurate measurement of the new generation of oral anticoagulants such as dabigatran and rivaroxaban in patients' plasma my provide important information in different clinical circumstances such as in the case of suspicion of overdose, when patients switch from existing oral anticoagulant, in patients with hepatic or renal impairment, by concomitant use of interaction drugs, or to assess anticoagulant concentration in patients' blood before major surgery. Here, we describe a quick and precise method to measure the coagulation inhibitors dabigatran and rivaroxaban using ultra-performance liquid chromatography electrospray ionization-tandem mass spectrometry in multiple reactions monitoring (MRM) mode (UPLC-MRM MS). Internal standards (ISs) were added to the sample and after protein precipitation; the sample was separated on a reverse phase column. After ionization of the analytes the ions were detected using electrospray ionization-tandem mass spectrometry. Run time was 2.5 minutes per injection. Ion suppression was characterized by means of post-column infusion. The calibration curves of dabigatran and rivaroxaban were linear over the working range between 0.8 and 800 μg/L (r >0.99). Limits of detection (LOD) in the plasma matrix were 0.21 μg/L for dabigatran and 0.34 μg/L for rivaroxaban, and lower limits of quantification (LLOQ) in the plasma matrix were 0.46 μg/L for dabigatran and 0.54 μg/L for rivaroxaban. The intraassay coefficients of variation (CVs) for dabigatran and rivaroxaban were method comparison between our UPLC-MRM MS method, the commercially available automated Direct Thrombin Inhibitor assay (DTI assay) for dabigatran measurement from CoaChrom Diagnostica, as well as the automated anti-Xa assay for rivaroxaban measurement from Chromogenix both performed by ACL-TOP showed a high degree of correlation. However, UPLC-MRM MS measurement of dabigatran and rivaroxaban has a much better selectivity than classical functional

  20. Recombinant human tissue factor pathway inhibitor exerts anticoagulant, anti-inflammatory and antimicrobial effects in murine pneumococcal pneumonia

    NARCIS (Netherlands)

    van den Boogaard, F. E.; Brands, X.; Schultz, M. J.; Levi, M. [=Marcel M.; Roelofs, J. J. T. H.; van 't Veer, C.; van der Poll, T.

    2011-01-01

    Background: Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia and a major cause of sepsis. Recombinant human tissue factor pathway inhibitor (rh-TFPI) attenuates sepsis-induced coagulation and has been evaluated in clinical trials involving patients

  1. The protein concentration of blood coagulation factor VII can be measured equally well in plasma and serum

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Overgaard, K; Gram, J

    1995-01-01

    In the Northwick Park Heart Study, the coagulant activity of factor VII (FVII:C) has been identified as a risk marker of ischaemic heart disease. In the fasting state, the protein concentration of FVII (FVII:Ag) might be an even better risk marker, because of the low coefficient of variation...

  2. Coagulation Profile as a Risk Factor for 30-day Morbidity Following Cervical Laminectomy and Fusion.

    Science.gov (United States)

    Bronheim, Rachel S; Oermann, Eric K; Cho, Samuel K; Caridi, John M

    2018-02-15

    Retrospective analysis of prospectively collected data. The aim of this study was to determine the ability of abnormal coagulation profile to predict adverse events following posterior cervical laminectomy and fusion (PCLF). PCLF is an increasingly common procedure used to treat a variety of traumatic and degenerative spinal conditions. Abnormal coagulation profile is associated with postoperative adverse events, including blood transfusion. There is a paucity of literature that specifically addresses the relationship between coagulation profile and complications following PCLF. ACS-NSQIP was utilized to identify patients undergoing PCLF between 2006 and 2013. A total of 3546 patients met inclusion criteria. Multivariate analysis was utilized to identify associations between abnormal coagulation profile and postoperative complications. Membership in the low-platelet cohort was an independent risk factor for myocardial infarction (Odds Ratio (OR) = 5.4 [1.0, 29.1], P = 0.049) and bleeding transfusion (OR = 2.0 [1.2, 3.4], P = 0.011). Membership in the high international normalized ratio group was an independent risk factor for pneumonia (OR = 6.3 [2.5, 16.1], P 48 hours (OR = 6.5 [2.3, 18.4], P 48 hours (OR = 4.8 [1.9, 12.4], P = 0.001), cerebrovascular accident/stroke with neurological deficit (OR = 24.8 [2.9, 210.6], P = 0.003), bleeding transfusion (OR = 2.1 [1.1, 4.1], P = 0.032), reoperation (OR = 3.6 [1.4, 9.3], P = 0.008), and sepsis (OR = 3.4 [1.1, 10.4], P = 0.031). This is the first large study to document abnormal coagulation profile as an independent predictor of outcomes following PCLF. Abnormal coagulation profile represents a predictor of complications that can be medically mitigated, and is therefore a valuable parameter to assess preoperatively. Coagulation profile should continue to play a role in targeting patients for risk stratification, preoperative optimization, and

  3. Acquired Factor XI Inhibitor Presenting as Spontaneous Bilateral Subdural Hematoma in an Elderly Patient

    Directory of Open Access Journals (Sweden)

    Natale Vazzana

    2014-01-01

    Full Text Available Development of autoantibodies against coagulation factors is an uncommon bleeding disorder associated with cancer, autoimmune conditions, pregnancy, or no apparent disease. Spontaneous FVIII inhibitors are the most frequently encountered; those against FXI have been only anecdotally reported. We report a case of acquired FXI inhibitor presenting as fatal intracranial spontaneous bleeding in an elderly patient with history of cancer and previous transfusions. Few cases of acquired FXI inhibitor have been reported in association with connective tissue disease, cancer, or surgery. Bleeding includes mucocutaneous bleeding, postsurgical hemorrhage, or life-threatening events. Treatment consists of arresting the bleeding and inhibitor eradication. High degree of suspicion is essential to promptly diagnose and treat this uncommon condition.

  4. Coagulation factor XI improves host defence during murine pneumonia-derived sepsis independent of factor XII activation

    NARCIS (Netherlands)

    Stroo, Ingrid; Zeerleder, Sacha; Ding, Chao; Luken, Brenda M.; Roelofs, Joris J. T. H.; de Boer, Onno J.; Meijers, Joost C. M.; Castellino, Francis J.; van 't Veer, Cornelis; van der Poll, Tom

    2017-01-01

    Bacterial pneumonia, the most common cause of sepsis, is associated with activation of coagulation. Factor XI (FXI), the key component of the intrinsic pathway, can be activated via factor XII (FXII), part of the contact system, or via thrombin. To determine whether intrinsic coagulation is involved

  5. EFFECTS OF ORAL CONTRACEPTIVES ON COAGULATING FACTORS

    Directory of Open Access Journals (Sweden)

    H.R. Sadeghipour Roudsari.

    1997-06-01

    Full Text Available Thirty young, healthy, nonsmoking women (mean age approximately 28 years taking low-dose oral contraceptive pills were recruited for the study of the effects of these pills on coagulating factors. Twenty subjects were taking LD pill (Ethinyl estradiol 0.03 mg, levonorgestrel 0.15 mg and 10 others were taking Cilest (Ethinyl estradiol 0.035 mg, Norgestimate 0.25 mg for six months. The control subjects did not receive any oral contraceptives or other medications. Our results showed that:"n1. There is no significant difference between the effects of LD and Cilest (with a different progestin content on coagulating factors."n2. No significant changes were observed between both LD users and controls in PT, APTT, and fibrinogen levels."n3. No significant changes were observed between both Cilest users and controls in PT, APTT, and fibrinogen levels."n

  6. Systems biology of coagulation initiation: kinetics of thrombin generation in resting and activated human blood.

    Directory of Open Access Journals (Sweden)

    Manash S Chatterjee

    2010-09-01

    Full Text Available Blood function defines bleeding and clotting risks and dictates approaches for clinical intervention. Independent of adding exogenous tissue factor (TF, human blood treated in vitro with corn trypsin inhibitor (CTI, to block Factor XIIa will generate thrombin after an initiation time (T(i of 1 to 2 hours (depending on donor, while activation of platelets with the GPVI-activator convulxin reduces T(i to ∼20 minutes. Since current kinetic models fail to generate thrombin in the absence of added TF, we implemented a Platelet-Plasma ODE model accounting for: the Hockin-Mann protease reaction network, thrombin-dependent display of platelet phosphatidylserine, VIIa function on activated platelets, XIIa and XIa generation and function, competitive thrombin substrates (fluorogenic detector and fibrinogen, and thrombin consumption during fibrin polymerization. The kinetic model consisting of 76 ordinary differential equations (76 species, 57 reactions, 105 kinetic parameters predicted the clotting of resting and convulxin-activated human blood as well as predicted T(i of human blood under 50 different initial conditions that titrated increasing levels of TF, Xa, Va, XIa, IXa, and VIIa. Experiments with combined anti-XI and anti-XII antibodies prevented thrombin production, demonstrating that a leak of XIIa past saturating amounts of CTI (and not "blood-borne TF" alone was responsible for in vitro initiation without added TF. Clotting was not blocked by antibodies used individually against TF, VII/VIIa, P-selectin, GPIb, protein disulfide isomerase, cathepsin G, nor blocked by the ribosome inhibitor puromycin, the Clk1 kinase inhibitor Tg003, or inhibited VIIa (VIIai. This is the first model to predict the observed behavior of CTI-treated human blood, either resting or stimulated with platelet activators. CTI-treated human blood will clot in vitro due to the combined activity of XIIa and XIa, a process enhanced by platelet activators and which proceeds

  7. Vitamin K: from coagulation to calcification.

    Science.gov (United States)

    Paakkari, Ilari

    Vitamin K is not only essential for the synthesis of coagulation factors in the liver, but it also strengthens the bones and prevents calcification of the arteries. These effects are mediated through the same mechanism, i.e. carboxylation of Gla target proteins. The discovery of novel Gla proteins that are not associated with blood coagulation or calcium metabolism indicates that vitamin K has additional effects in the pancreas and the central nervous system, for example. As dietary supplements, vitamin K1 of plant origin and vitamins K2 of bacterial origin may exert different effects.

  8. Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1 in Human Macrophages

    Directory of Open Access Journals (Sweden)

    G. Chinetti-Gbaguidi

    2016-01-01

    Full Text Available Tissue factor (TF is the initiator of the blood coagulation cascade after interaction with the activated factor VII (FVIIa. Moreover, the TF/FVIIa complex also activates intracellular signalling pathways leading to the production of inflammatory cytokines. The TF/FVIIa complex is inhibited by the tissue factor pathway inhibitor-1 (TFPI-1. Peroxisome proliferator-activated receptor gamma (PPARγ is a transcription factor that, together with PPARα and PPARβ/δ, controls macrophage functions. However, whether PPARγ activation modulates the expression of TFP1-1 in human macrophages is not known. Here we report that PPARγ activation increases the expression of TFPI-1 in human macrophages in vitro as well as in vivo in circulating peripheral blood mononuclear cells. The induction of TFPI-1 expression by PPARγ ligands, an effect shared by the activation of PPARα and PPARβ/δ, occurs also in proinflammatory M1 and in anti-inflammatory M2 polarized macrophages. As a functional consequence, treatment with PPARγ ligands significantly reduces the inflammatory response induced by FVIIa, as measured by variations in the IL-8, MMP-2, and MCP-1 expression. These data identify a novel role for PPARγ in the control of TF the pathway.

  9. Overuse of preoperative laboratory coagulation testing and ABO blood typing: a French national study.

    Science.gov (United States)

    Beloeil, H; Ruchard, D; Drewniak, N; Molliex, S

    2017-12-01

    Following publication of guidelines on routine preoperative tests, the French Society of Anaesthesiology and Intensive Care (SFAR), in association with French national public health insurance, conducted a survey to evaluate adherence to guidelines and the economic consequences. Using the French Hospital Discharge Database and National Health Insurance Information system, tests performed during the 30 days before surgery were analysed for two situations: (1) standard laboratory coagulation tests and ABO blood typing in children able to walk and scheduled for tonsillectomy/adenoidectomy; and (2) ABO blood typing in adults before laparoscopic cholecystectomy, thyroidectomy, lumbar discectomy or breast surgery. Guidelines do not recommend any preoperative tests in these settings. Between 2013 and 2015, a coagulation test was performed in 49% of the 241 017 children who underwent tonsillectomy and 39% of the 133 790 children who underwent adenoidectomy. A similar pattern was observed for ABO blood typing although re-operation rates for bleeding on the first postoperative day were very low (0.12-0.31% for tonsillectomy and 0.01-0.02% for adenoidectomy). Between 2012 and 2015, ABO blood typing was performed in 32-45% of the 1 114 082 patients who underwent one of the four selected procedures. The transfusion rate was very low (0.02-0.31%). The mean cost for the four procedures over the 4 yr period was €5 310 000 (sd €325 000). Standard laboratory coagulation tests and ABO blood typing are still routinely prescribed before surgery and anaesthesia despite current guidelines. This over-prescription represents a high and unnecessary cost, and should therefore be addressed. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  10. Nucleotide sequence of the gene coding for human factor VII, a vitamin K-dependent protein participating in blood coagulation

    International Nuclear Information System (INIS)

    O'Hara, P.J.; Grant, F.J.; Haldeman, B.A.; Gray, C.L.; Insley, M.Y.; Hagen, F.S.; Murray, M.J.

    1987-01-01

    Activated factor VII (factor VIIa) is a vitamin K-dependent plasma serine protease that participates in a cascade of reactions leading to the coagulation of blood. Two overlapping genomic clones containing sequences encoding human factor VII were isolated and characterized. The complete sequence of the gene was determined and found to span about 12.8 kilobases. The mRNA for factor VII as demonstrated by cDNA cloning is polyadenylylated at multiple sites but contains only one AAUAAA poly(A) signal sequence. The mRNA can undergo alternative splicing, forming one transcript containing eight segments as exons and another with an additional exon that encodes a larger prepro leader sequence. The latter transcript has no known counterpart in the other vitamin K-dependent proteins. The positions of the introns with respect to the amino acid sequence encoded by the eight essential exons of factor VII are the same as those present in factor IX, factor X, protein C, and the first three exons of prothrombin. These exons code for domains generally conserved among members of this gene family. The comparable introns in these genes, however, are dissimilar with respect to size and sequence, with the exception of intron C in factor VII and protein C. The gene for factor VII also contains five regions made up of tandem repeats of oligonucleotide monomer elements. More than a quarter of the intron sequences and more than a third of the 3' untranslated portion of the mRNA transcript consist of these minisatellite tandem repeats

  11. Coagulation Factor Tests: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... K. Brunner & Suddarth's Handbook of Laboratory and Diagnostic Tests. 2nd Ed, Kindle. Philadelphia: Wolters Kluwer Health, Lippincott Williams & Wilkins; c2014. Coagulation Factor Assay; 156–7 p. ...

  12. Comparison of two blood sampling techniques for the determination of coagulation parameters in the horse: Jugular venipuncture and indwelling intravenous catheter.

    Science.gov (United States)

    Mackenzie, C J; McGowan, C M; Pinchbeck, G; Carslake, H B

    2018-05-01

    Evaluation of coagulation status is an important component of critical care. Ongoing monitoring of coagulation status in hospitalised horses has previously been via serial venipuncture due to concerns that sampling directly from the intravenous catheter (IVC) may alter the accuracy of the results. Adverse effects such as patient anxiety and trauma to the sampled vessel could be avoided by the use of an indwelling IVC for repeat blood sampling. To compare coagulation parameters from blood obtained by jugular venipuncture with IVC sampling in critically ill horses. Prospective observational study. A single set of paired blood samples were obtained from horses (n = 55) admitted to an intensive care unit by direct jugular venipuncture and, following removal of a presample, via an indwelling IVC. The following coagulation parameters were measured on venipuncture and IVC samples: whole blood prothrombin time (PT), fresh plasma PT and activated partial thromboplastin time (aPTT) and stored plasma antithrombin activity (AT) and fibrinogen concentration. D-dimer concentration was also measured in some horses (n = 22). Comparison of venipuncture and IVC results was performed using Lin's concordance correlation coefficient. Agreement between paired results was assessed using Bland Altman analysis. Correlation was substantial and agreement was good between sample methods for all parameters except AT and D-dimers. Each coagulation parameter was tested using only one assay. Sampling was limited to a convenience sample and timing of sample collection was not standardised in relation to when the catheter was flushed with heparinised saline. With the exception of AT and D-dimers, coagulation parameters measured on blood samples obtained via an IVC have clinically equivalent values to those obtained by jugular venipuncture. © 2017 EVJ Ltd.

  13. Further insight into the roles of the glycans attached to human blood protein C inhibitor

    DEFF Research Database (Denmark)

    Sun, Wei; Parry, Simon; Ubhayasekera, Wimal

    2010-01-01

    Protein C inhibitor (PCI) is a 57-kDa glycoprotein that exists in many tissues and secretions in human. As a member of the serpin superfamily of proteins it displays unusually broad protease specificity. PCI is implicated in the regulation of a wide range of processes, including blood coagulation......, fertilization, prevention of tumors and pathogen defence. It has been reported that PCI isolated from human blood plasma is highly heterogeneous, and that this heterogeneity is caused by differences in N-glycan structures, N-glycosylation occupancy, and the presence of two forms that differ by the presence...... or absence of 6 amino acids at the amino-terminus. In this study we have verified that such heterogeneity exists in PCI purified from single individuals, and that individuals of two different ethnicities possess a similar PCI pattern, verifying that the micro-heterogeneity is conserved among humans...

  14. Prognostic significance of blood coagulation tests in carcinoma of the lung and colon.

    Science.gov (United States)

    Wojtukiewicz, M Z; Zacharski, L R; Moritz, T E; Hur, K; Edwards, R L; Rickles, F R

    1992-08-01

    Blood coagulation test results were collected prospectively in patients with previously untreated, advanced lung or colon cancer who entered into a clinical trial. In patients with colon cancer, reduced survival was associated (in univariate analysis) with higher values obtained at entry to the study for fibrinogen, fibrin(ogen) split products, antiplasmin, and fibrinopeptide A and accelerated euglobulin lysis times. In patients with non-small cell lung cancer, reduced survival was associated (in univariate analysis) with higher fibrinogen and fibrin(ogen) split products, platelet counts and activated partial thromboplastin times. In patients with small cell carcinoma of the lung, only higher activated partial thromboplastin times were associated (in univariate analysis) with reduced survival in patients with disseminated disease. In multivariate analysis, higher activated partial thromboplastin times were a significant independent predictor of survival for patients with non-small cell lung cancer limited to one hemithorax and with disseminated small cell carcinoma of the lung. Fibrin(ogen) split product levels were an independent predictor of survival for patients with disseminated non-small cell lung cancer as were both the fibrinogen and fibrinopeptide A levels for patients with disseminated colon cancer. These results suggest that certain tests of blood coagulation may be indicative of prognosis in lung and colon cancer. The heterogeneity of these results suggests that the mechanism(s), intensity, and pathophysiological significance of coagulation activation in cancer may differ between tumour types.

  15. An assessment of thromboelastometry to monitor blood coagulation and guide transfusion support in liver transplantation.

    Science.gov (United States)

    Blasi, Annabel; Beltran, Joan; Pereira, Arturo; Martinez-Palli, Graciela; Torrents, Abiguei; Balust, Jaume; Zavala, Elizabeth; Taura, Pilar; Garcia-Valdecasas, Juan-Carlos

    2012-09-01

    Rotation thromboelastometry (TEM) has been proposed as a convenient alternative to standard coagulation tests in guiding the treatment of coagulopathy during orthotopic liver transplantation (OLT). This study was aimed at assessing the value of TEM in monitoring blood coagulation and guide transfusion support in OLT. Standard coagulation and TEM (EXTEM and FIBTEM) tests were performed at four preestablished intraoperative time points in 236 OLTs and prospectively recorded in a dedicated database together with the main operative and transfusion data. Transfusion thresholds were based on standard coagulation tests. Spearman's rank correlation (ρ), linear regression, and receiver operating characteristic curves were used when appropriate. EXTEM maximum clot firmness (MCF(EXTEM)) was the TEM variable that best correlated with the platelet (PLT) and fibrinogen levels (ρ = 0.62 and ρ = 0.69, respectively). MCF(FIBTEM) correlated with fibrinogen level (ρ = 0.70). EXTEM clot amplitude at 10 minutes (A10(EXTEM)) was a good linear predictor of MCF(EXTEM) (R(2) =0.93). The cutoff values that best predicted the transfusion threshold for PLTs and fibrinogen were A10(EXTEM) = 35 mm and A10(FIBTEM) = 8 mm. At these values, the negative and positive predictive accuracies of TEM to predict the transfusion thresholds were 95 and 27%, respectively. A10(EXTEM) is an adequate TEM variable to guide therapeutic decisions during OLT. Patients with A10(EXTEM) of greater than 35 mm are unlikely to bleed because of coagulation deficiencies, but using A10(EXTEM) of not more than 35 mm as the sole transfusion criterion can lead to unnecessary utilization of PLTs and fibrinogen-rich products. © 2012 American Association of Blood Banks.

  16. The effect of a new impregnated gauze containing bentonite and halloysite minerals on blood coagulation and wound healing.

    Science.gov (United States)

    Alavi, Mehrosadat; Totonchi, Alireza; Okhovat, Mohammad Ali; Motazedian, Motahareh; Rezaei, Peyman; Atefi, Mohammad

    2014-12-01

    In recent years, a wide variety of research has been carried out in the field of novel technologies to stop severe bleeding. In several studies, coagulation properties of minerals such as zeolite, bentonite and halloysite have been proven. In this study, the effect of a new impregnated sterile gauze containing bentonite and halloysite minerals was studied on blood coagulation and wound healing rate in male Wistar rats. Initially, impregnated sterile gauze was prepared from the mixture of bentonite and halloysite minerals and petroleum jelly (Vaseline). Then, the effect of gauze was studied on the blood coagulation time and wound healing process in 40 Wistar rats. SPSS software was used for data analysis and P values less than 0.05 were considered significant. The coagulation time of 81.10 ± 2.532 s in the control group and 33.00 ± 1.214 s in the study group (bentonite-halloysite treated) were reported (P halloysite impregnated sterile gauze significantly decreases the clotting time and increase the wound healing rate.

  17. The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity.

    Directory of Open Access Journals (Sweden)

    Ashis K Mukherjee

    Full Text Available Proteases from Russell's viper venom (RVV induce a variety of toxic effects in victim. Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. These proteases were found to be different from previously reported factor V activators isolated from snake venoms. These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. Their Km and Vmax values towards fibrinogen were determined in the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein, respectively. On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis.

  18. The interplay between platelets and coagulation

    NARCIS (Netherlands)

    Weeterings, C.

    2009-01-01

    Platelet activation and blood coagulation are two processes often studied separately, but which cannot be seen independently from each other. Platelets play a pivotal role in coagulation, not only by providing negatively charged phospholipids, but also in localizing the coagulation process from a

  19. Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays.

    Science.gov (United States)

    Lindahl, Tomas L; Baghaei, Fariba; Blixter, Inger Fagerberg; Gustafsson, Kerstin M; Stigendal, Lennart; Sten-Linder, Margareta; Strandberg, Karin; Hillarp, Andreas

    2011-02-01

    Dabigatran is an oral, reversible thrombin inhibitor that has shown promising results in large clinical trials. Laboratory monitoring is not needed but the effects on common coagulation assays are incompletely known. Dabigatran was added to plasma from healthy subjects in the concentration range 0-1,000 μg/l and analysed using several reagents for activated thromboplastin time (APTT), prothrombin time (PT), fibrinogen, antithrombin, and activated protein C resistance. Typical trough concentrations are about 50 μg/l, peak concentrations 100-300 μg/l. At 100 μg/l all APTT-results were prolonged. The concentration required to double APTT ranged between 227 and 286 μg/l, the responses for all five reagents were similar. PT-reagents were much less affected with almost no samples above INR 1.2 at 100 μg/l. The effect was sample dilution dependent with PT Quick type more sensitive than PT Owren type methods. If a patient on dabigatran has prolonged APTT, >90 seconds, and Quick PT INR>2 or Owren PT INR>1.5 over-dosing or accumulation of dabigatran should be considered. Two of four fibrinogen reagents underestimated the fibrinogen concentration considerably at expected peak concentration. Methods based on inhibition of thrombin over-estimated the antithrombin concentration, but not Xa-based. The APC-resistance methods over-estimated the APC-ratio, which may lead to miss-classification of factor V Leiden patients as being normal. Different coagulation assays, and even different reagents within an assay group, display variable effects at therapeutic concentrations of dabigatran. Some of these assay variations are of clinical importance, thus knowledge is needed for a correct interpretation of results.

  20. Fasxiator, a novel factor XIa inhibitor from snake venom, and its site-specific mutagenesis to improve potency and selectivity.

    Science.gov (United States)

    Chen, W; Carvalho, L P D; Chan, M Y; Kini, R M; Kang, T S

    2015-02-01

    Bleeding remains a major limitation of standard anticoagulant drugs that target the extrinsic and common coagulation pathways. Recently, intrinsic coagulation factors are increasingly being investigated as alternative targets for developing anticoagulant drugs with lower bleeding risk. Goals were to (i) identify novel anticoagulants selectively targeting intrinsic coagulation pathway and (ii) characterize and further improve the properties of the identified anticoagulants. We have isolated and sequenced a specific factor XIa (FXIa) inhibitor, henceforth named Fasxiator, from the venom of the banded krait snake, Bungarus fasciatus. It is a Kunitz-type protease inhibitor that prolonged activated partial thromboplastin time without significant effects on prothrombin time. Fasxiator was recombinantly expressed (rFasxiator), purified, and characterized to be a slow-type inhibitor of FXIa that exerts its anticoagulant activities (doubled activated partial thromboplastin time at ~ 3 μmol L(-1) ) by selectively inhibiting human FXIa in in vitro assays. A series of mutants were subsequently generated to improve the potency and selectivity of recombinant rFasxiator. rFasxiatorN17R,L19E showed the best balance between potency (IC50 ~ 1 nmol L(-1) ) and selectivity (> 100 times). rFasxiatorN17R,L19E is a competitive slow-type inhibitor of FXIa (Ki  = 0.86 nmol L(-1) ), possesses anticoagulant activity that is ~ 10 times stronger in human plasma than in murine plasma, and prolonged the occlusion time of mice carotid artery in FeCl3 -induced thrombosis models. We have isolated an exogenous FXIa specific inhibitor, engineered it to improve its potency by ~ 1000 times and demonstrated its in vitro and in vivo efficacy. These proof-of-principle data supported the further development of Fasxiator as a novel anticoagulant candidate. © 2014 International Society on Thrombosis and Haemostasis.

  1. Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

    Directory of Open Access Journals (Sweden)

    Reed JW

    2016-10-01

    Full Text Available James W Reed Morehouse School of Medicine, Atlanta, GA, USA Abstract: SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM. These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin on BP in patients with T2DM. Boolean searches were conducted that included terms related to BP or hypertension with terms for SGLT2 inhibitors, canagliflozin, dapagliflozin, or empagliflozin using PubMed, Google, and Google Scholar. Data from numerous randomized controlled trials of SGLT2 inhibitors in patients with T2DM demonstrated clinically relevant reductions in both systolic and diastolic BP, assessed via seated office measurements and 24-hour ambulatory BP monitoring. Observed BP lowering was not associated with compensatory increases in heart rate. Circadian BP rhythm was also maintained. The mechanism of SGLT2 inhibitor-associated BP reduction is not fully understood, but is assumed to be related to osmotic diuresis and natriuresis. Other factors that may also contribute to BP reduction include SGLT2 inhibitor-associated decreases in body weight and reduced arterial stiffness. Local inhibition of the renin–angiotensin–aldosterone system secondary to increased delivery of sodium to the juxtaglomerular apparatus during SGLT2 inhibition has also been postulated. Although SGLT2 inhibitors are not indicated as BP-lowering agents, the modest decreases in systolic and diastolic BP observed with SGLT2 inhibitors may provide an extra clinical advantage for the majority of patients with T2DM, in addition to improving blood glucose

  2. Rare coagulation disorders: fibrinogen, factor VII and factor XIII.

    Science.gov (United States)

    de Moerloose, P; Schved, J-F; Nugent, D

    2016-07-01

    Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII. © 2016 John Wiley & Sons Ltd.

  3. Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice.

    Science.gov (United States)

    Verma, Dheeraj; Moghimi, Babak; LoDuca, Paul A; Singh, Harminder D; Hoffman, Brad E; Herzog, Roland W; Daniell, Henry

    2010-04-13

    To address complications of pathogenic antibody or life-threatening anaphylactic reactions in protein replacement therapy for patients with hemophilia or other inherited protein deficiencies, we have developed a prophylactic protocol using a murine hemophilia B model. Oral delivery of coagulation factor IX fused with cholera toxin beta-subunit (with or without a furin cleavage site; CTB-FFIX or CTB-FIX), expressed in chloroplasts (up to 3.8% soluble protein or 0.4 mg/g leaf tissue), bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies (undetectable or up to 100-fold less than controls). Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous F.IX. Whereas only 20-25% of control animals survived after six to eight F.IX doses, 90-93% of F.IX-fed mice survived 12 injections without signs of allergy or anaphylaxis. Immunostaining confirmed delivery of F.IX to Peyer's patches in the ileum. Within 2-5 h, feeding of CTB-FFIX additionally resulted in systemic delivery of F.IX antigen. This high-responder strain of hemophilia B mice represents a new animal model to study anaphylactic reactions. The protocol was effective over a range of oral antigen doses (equivalent to 5-80 microg recombinant F.IX/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months (approximately 40% life span of this mouse strain). Oral antigen administration caused a deviant immune response that suppressed formation of IgE and inhibitory antibodies. This cost-effective and efficient approach of antigen delivery to the gut should be applicable to several genetic diseases that are prone to pathogenic antibody responses during treatment.

  4. Sphingosine 1-Phosphate as a Link between Blood Coagulation and Inflammation

    Directory of Open Access Journals (Sweden)

    Bernhard Hermann Rauch

    2014-06-01

    Full Text Available Sphingosine 1-phosphate (S1P is a multifunctional signaling lipid generated from sphingosine by sphingosine kinases. S1P formation has been shown in numerous cells in the circulation, including platelets, vascular endothelial and smooth muscle cells and monocytes. S1P also exerts multiple effects on these cells, i.e. cell proliferation and migration, activation of proinflammatory signaling pathways and release of additional inflammatory mediators. Similar activities and targets have also been identified for activated clotting factors such as thrombin or the activated factor-X (FXa, suggesting a possible involvement of S1P in thrombus-associated cellular signaling and thrombin-induced inflammatory reactions. Several levels of S1P-mediated, thrombin /FXa-induced signaling have already been identified: regulation of sphingosine kinase expression and activity, stimulation of S1P release from platelets and other cells and, possibly regulation of S1P-receptors on target cells. This review summarizes the current state of knowledge about S1P as a clotting factor-regulated molecular link between blood coagulation and inflammation. It is concluded that S1P might represent an until now underestimated lipid mediator of inflammatory reactions following activation of the clotting system and, in this context, also involved in the development and progression of atherosclerosis.

  5. Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

    Science.gov (United States)

    Reed, James W

    2016-01-01

    SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM). These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP) lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin) on BP in patients with T2DM. Boolean searches were conducted that included terms related to BP or hypertension with terms for SGLT2 inhibitors, canagliflozin, dapagliflozin, or empagliflozin using PubMed, Google, and Google Scholar. Data from numerous randomized controlled trials of SGLT2 inhibitors in patients with T2DM demonstrated clinically relevant reductions in both systolic and diastolic BP, assessed via seated office measurements and 24-hour ambulatory BP monitoring. Observed BP lowering was not associated with compensatory increases in heart rate. Circadian BP rhythm was also maintained. The mechanism of SGLT2 inhibitor-associated BP reduction is not fully understood, but is assumed to be related to osmotic diuresis and natriuresis. Other factors that may also contribute to BP reduction include SGLT2 inhibitor-associated decreases in body weight and reduced arterial stiffness. Local inhibition of the renin–angiotensin–aldosterone system secondary to increased delivery of sodium to the juxtaglomerular apparatus during SGLT2 inhibition has also been postulated. Although SGLT2 inhibitors are not indicated as BP-lowering agents, the modest decreases in systolic and diastolic BP observed with SGLT2 inhibitors may provide an extra clinical advantage for the majority of patients with T2DM, in addition to improving blood glucose control. PMID:27822054

  6. The role of stress hormones in the relationship between resting blood pressure and coagulation activity.

    Science.gov (United States)

    Wirtz, Petra H; Ehlert, Ulrike; Emini, Luljeta; Rüdisüli, Katharina; Groessbauer, Sara; Mausbach, Brent T; von Känel, Roland

    2006-12-01

    Systemic hypertension confers a hypercoagulable state. We hypothesized that resting mean blood pressure (MBP) interacts with stress hormones in predicting coagulation activity at rest and with acute mental stress. We measured plasma clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, epinephrine and norepinephrine, and saliva cortisol in 42 otherwise healthy normotensive and hypertensive medication-free men (mean age 43 +/- 14 years) at rest, immediately after stress, and twice during 60 min of recovery from stress. At rest, the MBP-by-epinephrine interaction predicted FVII:C (beta = -0.33, P AUC) predicted D-dimer AUC (beta = 0.34, P = 0.04) independent of MBP. The MBP-by-epinephrine AUC interaction predicted FVII:C AUC (beta = 0.28) and fibrinogen AUC (beta = -0.30), and the MBP-by-norepinephrine AUC interaction predicted FVIII:C AUC (beta = -0.28), all with borderline significance (Ps < 0.09) and independent of age and BMI. MBP significantly altered the association between stress hormones and coagulation activity at rest and, with borderline significance, across the entire stress and recovery interval. Independent of MBP, catecholamines were associated with procoagulant effects and cortisol reactivity dampened the acute procoagulant stress response.

  7. Expression of the human blood coagulation protein factor XIIIa in Saccharomyces cerevisiae: dependence of the expression levels from host-vector systems and medium conditions.

    Science.gov (United States)

    Bröker, M; Bäuml, O; Göttig, A; Ochs, J; Bodenbenner, M; Amann, E

    1991-03-01

    The human blood coagulation protein Factor XIIIa (FXIIIa) was expressed in Saccharomyces cerevisiae employing Escherichia coli-yeast shuttle vectors based on a 2-mu plasmid. Several factors affecting high production yield of recombinant FXIIIa were analysed. The use of the regulatable GAL-CYC1 hybrid promoter resulted in higher FXIIIa expression when compared with the constitutive ADCI promoter. Screening for suitable yeast strains for expression of FXIIIa under the transcriptional control of the GAL-CYC1 hybrid promoter revealed a broad spectrum of productivity. No obvious correlation between the expression rate and the genetic markers of the strains could be identified. The medium composition markedly influenced the FXIIIa expression rates. The expression of FXIIIa was strictly regulated by the carbon source. Glucose as the only sugar and energy source repressed the synthesis of FXIIIa, whereas addition of galactose induced FXIIIa expression. Special feeding schemes resulted in a productivity of up to 100 mg FXIIIa/l in shake flasks.

  8. Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.

    Science.gov (United States)

    Nadir, Yona; Brenner, Benjamin; Fux, Liat; Shafat, Itay; Attias, Judith; Vlodavsky, Israel

    2010-11-01

    Heparanase is an endo-β-D-glucuronidase dominantly involved in tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is involved in the regulation of the hemostatic system. Our hypothesis was that heparanase is directly involved in activation of the coagulation cascade. Activated factor X and thrombin were studied using chromogenic assays, immunoblotting and thromboelastography. Heparanase levels were measured by enzyme-linked immunosorbent assay. A potential direct interaction between tissue factor and heparanase was studied by co-immunoprecipitation and far-western assays. Interestingly, addition of heparanase to tissue factor and activated factor VII resulted in a 3- to 4-fold increase in activation of the coagulation cascade as shown by increased activated factor X and thrombin production. Culture medium of human embryonic kidney 293 cells over-expressing heparanase and its derivatives increased activated factor X levels in a non-enzymatic manner. When heparanase was added to pooled normal plasma, a 7- to 8-fold increase in activated factor X level was observed. Subsequently, we searched for clinical data supporting this newly identified role of heparanase. Plasma samples from 35 patients with acute leukemia at presentation and 20 healthy donors were studied for heparanase and activated factor X levels. A strong positive correlation was found between plasma heparanase and activated factor X levels (r=0.735, P=0.001). Unfractionated heparin and an inhibitor of activated factor X abolished the effect of heparanase, while tissue factor pathway inhibitor and tissue factor pathway inhibitor-2 only attenuated the procoagulant effect. Using co-immunoprecipitation and far-western analyses it was shown that heparanase interacts directly with tissue factor. Overall, our results support the notion that heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated

  9. Improved coagulation and blood conservation in the golden hours after cardiopulmonary bypass.

    Science.gov (United States)

    Beckmann, Scott R; Carlile, Dee; Bissinger, Randall C; Burrell, M; Winkler, Thomas; Shely, William W

    2007-06-01

    The Hemobag (HB) technique allows the open-heart team to safely concentrate the residual cardiopulmonary bypass (CPB) circuit contents and return a high volume of concentrated clotting factors and blood cells back to the patient as autotransfusion. Hematocrit, platelet count, fibrinogen concentration ([Fib]), prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR) were compared between two prospective convenience groups of cardiac surgical patients whose residual circuit blood was processed by the HB (n=10) or by the Cell Saver (CS; n=10) at two times after CPB: (a) after acute normovolemic hemodilution (ANH) infusion and protamine administration and (b) after admission to the intensive care unit (ICU), approximately 1 hour after CPB and HB content infusion. Minimal cell processing was also used in the HB patients to conserve blood. "Golden hours" is defined as the first few hours after CPB and protamine sulfate administration and extend into the ICU, when maintaining hemostasis is vital during cardiac surgery and is the most susceptible period for blood product administration and the opportunity to improve patient outcome. Except for PTT, all parameters changed significantly from the ANH infusion and protamine administration to approximately 1 hour after HB blood infusion and arrival in the ICU. Fibrinogen (p = .048) and hematocrit (p = .046) were significantly higher in the HB group compared with the CS group at the end of the golden hour despite infusion of significantly more allogeneic blood products (p = .070) and more washed red blood cells (RBCs; p = .001) in the CS group. All but one of the HB patients did not receive any allogeneic blood products during the golden hours. Use of the HB technique for salvaging blood is associated with significant increases in the patient's protein and cellular concentrations and lowered coagulation times in the important, first few golden hours after CPB, and except for one patient

  10. Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban-an oral, direct Factor Xa inhibitor.

    Science.gov (United States)

    Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Niederalt, Christoph; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Tanigawa, Takahiko; Lippert, Jörg

    2014-01-01

    The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2-3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban.

  11. Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban—an oral, direct Factor Xa inhibitor

    Science.gov (United States)

    Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Niederalt, Christoph; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Tanigawa, Takahiko; Lippert, Jörg

    2014-01-01

    The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2–3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban. PMID:25426077

  12. Trauma and Coagulation

    Directory of Open Access Journals (Sweden)

    Murat Yılmaz

    2011-08-01

    Full Text Available Bleeding and coagulation disorders related to trauma are pathological processes which are frequently seen and increase mortality. For the purpose, trauma patients should be protected from hypoperfusion, hypothermia, acidosis and hemodilution which may aggravate the increase in physiological responses to trauma as anticoagulation and fibrinolysis. Performing damage control surgery and resuscitation and transfusion of adequate blood and blood products in terms of amount and content as stated in protocols may increase the rate of survival. Medical treatments augmenting fibrin formation (fibrinogen, desmopressin, factor VIIa or preventing fibrin degradation (tranexamic acid have been proposed in selected cases but the efficacy of these agents in trauma patients are not proven. (Journal of the Turkish Society Intensive Care 2011; 9:71-6

  13. Chronic sleep deprivation markedly reduces coagulation factor VII expression

    Science.gov (United States)

    Pinotti, Mirko; Bertolucci, Cristiano; Frigato, Elena; Branchini, Alessio; Cavallari, Nicola; Baba, Kenkichi; Contreras-Alcantara, Susana; Ehlen, J. Christopher; Bernardi, Francesco; Paul, Ketema N.; Tosini, Gianluca

    2010-01-01

    Chronic sleep loss, a common feature of human life in industrialized countries, is associated to cardiovascular disorders. Variations in functional parameters of coagulation might contribute to explain this relationship. By exploiting the mouse model and a specifically designed protocol, we demonstrated that seven days of partial sleep deprivation significantly decreases (−30.5%) the thrombin generation potential in plasma evaluated upon extrinsic (TF/FVIIa pathway) but not intrinsic activation of coagulation. This variation was consistent with a decrease (−49.8%) in the plasma activity levels of factor VII (FVII), the crucial physiologicalal trigger of coagulation, which was even more pronounced at the liver mRNA level (−85.7%). The recovery in normal sleep conditions for three days completely restored thrombin generation and FVII activity in plasma. For the first time, we demonstrate that chronic sleep deprivation on its own reduces, in a reversible manner, the FVII expression levels, thus influencing the TF/FVIIa activation pathway efficiency. PMID:20418241

  14. Disseminated intravascular coagulation caused by moojenactivase, a procoagulant snake venom metalloprotease.

    Science.gov (United States)

    Sartim, Marco A; Cezarette, Gabriel N; Jacob-Ferreira, Anna L; Frantz, Fabiani G; Faccioli, Lucia H; Sampaio, Suely V

    2017-10-01

    Snake venom toxins that activate coagulation factors are key players in the process of venom-induced coagulopathy, and account for severe clinical manifestations. The present study applies a variety of biochemical, hematological, and histopathological approaches to broadly investigate the intravascular and systemic effects of moojenactivase (MooA), the first described PIIId subclass metalloprotease isolated from Bothrops sp. venom that activates coagulation factors. MooA induced consumption coagulopathy with high toxic potency, characterized by prolongation of prothrombin and activated partial thromboplastin time, consumption of fibrinogen and the plasma coagulation factors X and II, and thrombocytopenia. MooA promoted leukocytosis and expression of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-α, accompanied by tissue factor-dependent procoagulant activity in peripheral blood mononuclear cells. This metalloprotease also caused intravascular hemolysis, elevated plasma levels of creatine kinase-MB, aspartate transaminase, and urea/creatinine, and induced morphopathological alterations in erythrocytes, heart, kidney, and lungs associated with thrombosis and hemorrhage. Diagnosis of MooA-induced disseminated intravascular coagulation represents an important approach to better understand the pathophysiology of Bothrops envenomation and develop novel therapeutic strategies targeting hemostatic disturbances. Copyright © 2017. Published by Elsevier B.V.

  15. More efficient reversal of dabigatran inhibition of coagulation by activated prothrombin complex concentrate or recombinant factor VIIa than by four-factor prothrombin complex concentrate.

    Science.gov (United States)

    Lindahl, Tomas L; Wallstedt, Maria; Gustafsson, Kerstin M; Persson, Egon; Hillarp, Andreas

    2015-03-01

    The number of patients on antithrombotic treatment due to atrial fibrillation and venous thromboembolism is increasing fast due to an aging population. A growing proportion will be treated with novel oral anticoagulants, the first in clinical use was the direct oral thrombin inhibitor dabigatran (Pradaxa®). A small percentage of the patients on dabigatran will experience serious bleeding or be in need of urgent surgery. The aim of this study was to test the effects of different hemostatic agents in potentially reversing the anticoagulant effects in vitro in blood or platelet-rich plasma (PRP) spiked with dabigatran. Whole blood or PRP was spiked with the active substance dabigatran, 200 μg/L. We measured clotting time being induced by 1.4 pmol/L tissue factor using the instrument ReoRox2™ and initial clot growth velocity from a tissue factor covered surface using the instrument Thrombodynamics Analyzer T-2™. Dabigatran prolonged clotting time 5-fold but reduced clot growth velocity only slightly. The reversing effects of prothrombin complex concentrates (PCC), activated PCC (APCC) and recombinant activated factor VII (rFVIIa) were then tested. APCC (1.8 U/mL) reduced the prolonged clotting time by 1/3, rFVIIa (2 μg/L) only slightly (n = 10-20). The reduction was not significant using Mann-Whitney test but significant using t-test with Bonferronis' correction for multiple comparisons, whereas PCC (0.56 U/mL) had no effect on clotting time. APCC doubled initial clot growth velocity, although even more in the absence of dabigatran. In conclusion, APCC and rFVIIa, but not PCC, seem to reverse, at least partially, some effects of dabigatran on coagulation parameters. Systematic evaluation of case reports, registries and, ultimately, randomized clinical trials are needed to elucidate potential benefit for patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Theories About Blood Coagulation in the Writings of Ancient Greek Medico-philosophers.

    Science.gov (United States)

    Tsoucalas, Gregory; Karamanou, Marianna; Papaioannou, Theodoros G; Sgantzos, Markos

    2017-01-01

    Anaxagoras and Empedocles both established during the Presocratic era a pioneering theory for the creation of everything in the universe. Macrocosmos' impact through the "Four Elements Theory" explained the conglomeration of the blood inside the vessels. Hippocrates, who instituted the "Four Humours theory", clearly understood blood's coagulation and introduced the term "thrombus". Plato, Aristotle and Galen, all engaged with the clotting phenomenon trying to interpret it. After eons of inquiry, it was the innovative thinking of the ancient Greek medico philosophers that set the scientific bases towards the understanding of a process that had been analyzing until our era. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. The Inflammatory Actions of Coagulant and Fibrinolytic Proteases in Disease

    Directory of Open Access Journals (Sweden)

    Michael Schuliga

    2015-01-01

    Full Text Available Aside from their role in hemostasis, coagulant and fibrinolytic proteases are important mediators of inflammation in diseases such as asthma, atherosclerosis, rheumatoid arthritis, and cancer. The blood circulating zymogens of these proteases enter damaged tissue as a consequence of vascular leak or rupture to become activated and contribute to extravascular coagulation or fibrinolysis. The coagulants, factor Xa (FXa, factor VIIa (FVIIa, tissue factor, and thrombin, also evoke cell-mediated actions on structural cells (e.g., fibroblasts and smooth muscle cells or inflammatory cells (e.g., macrophages via the proteolytic activation of protease-activated receptors (PARs. Plasmin, the principle enzymatic mediator of fibrinolysis, also forms toll-like receptor-4 (TLR-4 activating fibrin degradation products (FDPs and can release latent-matrix bound growth factors such as transforming growth factor-β (TGF-β. Furthermore, the proteases that convert plasminogen into plasmin (e.g., urokinase plasminogen activator evoke plasmin-independent proinflammatory actions involving coreceptor activation. Selectively targeting the receptor-mediated actions of hemostatic proteases is a strategy that may be used to treat inflammatory disease without the bleeding complications of conventional anticoagulant therapies. The mechanisms by which proteases of the coagulant and fibrinolytic systems contribute to extravascular inflammation in disease will be considered in this review.

  18. Blood coagulation parameters and platelet indices: changes in normal and preeclamptic pregnancies and predictive values for preeclampsia.

    Directory of Open Access Journals (Sweden)

    Lei Han

    Full Text Available Preeclampsia (PE is an obstetric disorder with high morbidity and mortality rates but without clear pathogeny. The dysfunction of the blood coagulation-fibrinolysis system is a salient characteristic of PE that varies in severity, and necessitates different treatments. Therefore, it is necessary to find suitable predictors for the onset and severity of PE.We aimed to evaluate blood coagulation parameters and platelet indices as potential predictors for the onset and severity of PE.Blood samples from 3 groups of subjects, normal pregnant women (n = 79, mild preeclampsia (mPE (n = 53 and severe preeclampsia (sPE (n = 42, were collected during early and late pregnancy. The levels of coagulative parameters and platelet indices were measured and compared among the groups. The receiver-operating characteristic (ROC curves of these indices were generated, and the area under the curve (AUC was calculated. The predictive values of the selected potential parameters were examined in binary regression analysis.During late pregnancy in the normal pregnancy group, the activated partial thromboplastin time (APTT, prothrombin time (PT, thrombin time (TT and platelet count decreased, while the fibrinogen level and mean platelet volume (MPV increased compared to early pregnancy (p<0.05. However, the PE patients presented with increased APTT, TT, MPV and D-dimer (DD during the third trimester. In the analysis of subjects with and without PE, TT showed the largest AUC (0.743 and high predictive value. In PE patients with different severities, MPV showed the largest AUC (0.671 and ideal predictive efficiency.Normal pregnancy causes a maternal physiological hypercoagulable state in late pregnancy. PE may trigger complex disorders in the endogenous coagulative pathways and consume platelets and FIB, subsequently activating thrombopoiesis and fibrinolysis. Thrombin time and MPV may serve as early monitoring markers for the onset and severity of PE

  19. Changing the inhibitory specificity and function of Cucurbita maxima trypsin inhibitor-V by site-directed mutagenesis.

    Science.gov (United States)

    Wen, L; Lee, I; Chen, G; Huang, J K; Gong, Y; Krishnamoorthi, R

    1995-02-27

    Cucurbita maxima trypsin inhibitor-V (CMTI-V) is also a specific inhibitor of human blood coagulation factor beta-factor XIIa. A recombinant version of CMTI-V has allowed probing of roles of individual amino acid residues including the reactive site residue, lysine (P1), by site-directed mutagenesis. The K44R showed at least a 5-fold increase in inhibitory activity toward human beta-factor XIIa, while there was no change toward bovine trypsin. This result demonstrates that beta-factor-XIIa prefers an arginine residue over lysine residue, while trypsin is non-specific to lysine or arginine in its binding pocket. On the other hand, the specificity of CMTI-V could be changed from trypsin to chymotrypsin inhibition by mutation of the P1 residue to either leucine or methionine (K44L or K44M).

  20. Alterations of blood and blood coagulation by extracorporeal irradiation in leukemia and radiophosphor therapy in polycythemia

    International Nuclear Information System (INIS)

    Huhn, D.; Kaboth, W.; Theml, H.; Murr, H.; Schramm, W.; Leisner, B.

    1974-01-01

    Animal experiments prove a high radiation resistance of megakaryocytes and thrombocytes. Radiophosphorus is thought to influence mainly the megakaryocytes in their beginnings; an effect on the vessel system of the bone marrow is particularly to be discussed in the case of very early and quickly reversible drop in thrombocytes. In the very first week after radiophosphorus administration, a considerable drop in thrombocytes is already seen in some patients, the number of patients remaining the same during the following 3 weeks. After blood irradiation, the thrombocytes are for a certain period reduced due to the influence of the extracorporal circulation, but in general their number increases again during the following months. A considerable disfunction of the thrombocytes or a disturbed coagulation is not found either after radiophosphorus treatment or after extracorporal blood irradiation. (orig.) [de

  1. Coagulation system changes associated with susceptibility to infection in trauma patients.

    Science.gov (United States)

    Cole, Elaine; Davenport, Ross; De'Ath, Henry; De-Ath, Henry; Manson, Joanna; Brockamp, Thomas; Brohi, Karim

    2013-01-01

    Infection following trauma is associated with increased morbidity and mortality and is common following severe hemorrhage. There is a strong interaction between the coagulation and immunity. The objective of this study was to establish if there was an association between changes in coagulation status after hemorrhage and the subsequent incidence of infection. Prospective cohort study of adult injured patients presenting to a major trauma center during a 2-year period. Blood was drawn at 24 hours following admission and analyzed using functional thromboelastography testing and laboratory defined tests of coagulation and blood count. Patients were followed up for infectious episodes while in the hospital using Center for Disease Control definitions. A total of 158 patients were recruited; 71 (45%) developed infection and were older (44 years vs. 32 years, p = 0.01) and more severely injured (Injury Severity Score [ISS], 25 vs.10; p < 0.01). White blood cell counts at 24 hours were normal, and there was no difference between groups (both 9.6 × 10/(9)L). Protein C was lower in those with infection (70.2 IU/dL vs. 83.3 IU/dL, p = 0.02), with a dose-dependent increase in infection as levels of protein C decreased. Plasmin activation at 24 hours was also strongly associated with infection plasmin-antiplasmin (infection vs. no infection, 6,156 μg/L vs. 3,324 μg/L, p = 0.03). The infection cohort had overall 12% lower procoagulant levels (varied between factor VIII 6.4% and factor II 16.2%). There is a strong association between the status of the coagulation system after 24 hours and the development of infection following trauma. Improved early coagulation management may decrease infection rates in this patient group. Prognostic prospective study, level III.

  2. Experimental melanoma metastasis in lungs of mice with congenital coagulation disorders

    NARCIS (Netherlands)

    Brüggemann, Lois W.; Versteeg, Henri H.; Niers, Tatjana M.; Reitsma, Pieter H.; Spek, C. Arnold

    2008-01-01

    Experimental animal studies as well as clinical trials have shown that interventions targeting the blood coagulation cascade inhibit cancer cell metastasis. These data support the hypothesis that congenital prothrombotic disorders, like factor V Leiden, facilitate metastasis whereas bleeding

  3. Inventive activity of the Department of Protein Structure and Function of the Palladin Institute of Biochemistry of NAS of Ukraine. Part I. Development of the diagnostic methods for detection of hemostasis disorders and characterization of certain blood coagulation factors

    Directory of Open Access Journals (Sweden)

    V. M. Danilova

    2016-04-01

    Full Text Available The practical aspects of inventive activity of the Department of Protein Structure and Function of the Palladin Institute of Biochemistry, NAS of Ukraine are highlighted in this article. Through years of fundamental and applied researches of blood coagulation system proteins, initiated by luminaries of the world biochemistry O. V. Palladin and V. O. Belitser, the Department staff have developed a considerable number of methods, techniques and tests for the assessment of the state of the hemostasis system, which were approved in many clinics. In the first part of this work the authors describe the development of the diagnostic methods for identifying the homeostasis system disorders in detail, as well as characterize certain coagulation factors.

  4. Coagulation Profile as a Risk Factor for 30-Day Morbidity and Mortality Following Posterior Lumbar Fusion.

    Science.gov (United States)

    Bronheim, Rachel S; Oermann, Eric K; Cho, Samuel K; Caridi, John M

    2017-06-15

    A retrospective cohort study. The aim of this study was to identify associations between abnormal coagulation profile and postoperative morbidity and mortality in patients undergoing posterior lumbar fusion (PLF). The literature suggests that abnormal coagulation profile is associated with postoperative complications, notably the need for blood transfusion. However, there is little research that directly addresses the influence of coagulation profile on postoperative complications following PLF. The American College of Surgeons National Surgical Quality Improvement Program database (ACS-NSQIP) was utilized to identify patients undergoing PLF between 2006 and 2013. Nine thousand two hundred ninety-five patients met inclusion criteria. Multivariate analysis was utilized to identify associations between abnormal coagulation profile and postoperative complications. Low platelet count was an independent risk factor for organ space surgical site infections (SSIs) [odds ratio (OR) = 6.0, P 48 hours (OR = 4.5, P = 0.002), Acute renal failure (OR = 5.8, P = 0.007), transfusion (OR = 1.6, P risk factor for ventilation >48 hours (OR = 5.6, P = 0.002), cerebrovascular accident (CVA)/stroke with neurological deficit (OR = 5.1, P = 0.011), cardiac arrest (OR = 5.4, P = 0.030), transfusion (OR = 1.5, P = 0.020), and death (OR = 4.5, P = 0.050). High International Normalized Ration (INR) was an independent risk factor for pneumonia (OR = 8.7, P = 0.001), pulmonary embolism (OR = 5.6, P = 0.021), deep venous thrombosis/Thrombophlebitis (OR = 4.8, P = 0.011), septic shock (OR = 8.4, P = 0.048), and death (OR = 9.8, P = 0.034). Bleeding disorder was an independent risk factor for organ space SSI (OR = 5.4, P = 0.01), pneumonia (OR = 3.0, P = 0.023), and sepsis (OR = 4.4, P profile was an independent predictor of morbidity and mortality in patients

  5. Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

    Science.gov (United States)

    Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

    2013-07-01

    Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

  6. Plasma fractionation for blood products: isolation and purification of coagulating factors, albumin and immunoglobulin

    International Nuclear Information System (INIS)

    Siti Najila Mohd Janib; Shaharuddin Mohd; Wan Hamirul Bahrin Wan Kamal

    2005-01-01

    Approximately 12 million liters of human plasma are fractionated world-wide annually. However, with the market for clotting factors and other haemoderivatives steadily increasing from year to year, the amount processed will also increase correspondingly to keep up with the demand. In Malaysia, part of the need for the blood products are obtained commercially but a major portion of the requirement involves sending the plasma collected by the National Blood Centre to Australia for processing. Following purification and isolation of the blood products, they are sent back to Malaysia for local consumption. As yet there are no plasma fractionation plants in the South East Asia region, it would be advantageous to establish a local fractionation plant as it would be able to cater for local demands of the haemoderivatives and thus reduces the cost of importing these products. Besides, this facility will be able to provide contract fractionation services to the surrounding region. Early work in MINT has started in trying to purify plasma obtained from rats. Purification of the plasma was performed by using Sephadex G-25 column. Short term objective of this project is to develop the technique of extraction, fractionation and purification of blood products such as albumin, globulin and clotting factors (Factor VIII and Factor IX). The long term emphasis will be to scale up the production facility to a pilot plant stage and eventually to a national fractionation and purification plant. (Author)

  7. Thrombin activatable fibrinolysis inhibitor (TAFI in cord blood.

    Directory of Open Access Journals (Sweden)

    Krzysztof Góralczyk

    2007-03-01

    Full Text Available Thrombin activatable fibrinolysis inhibitor (TAFI is a plasma zymogene (procarboxypeptidase B which can decrease fibrinolysis and thus act as a haemostatic factor. TAFI is now extensively studied in many complications as well as in physiological and complicated pregnancy. The question we posed in the present study was whether TAFI antigen is present in cord blood plasma. The study group consisted of 38 parturient women, 26 primiparous and 12 multiparous with normal course of pregnancy and delivery. The cord blood was sampled from the cord vein, and the mother's blood from the antecubital vein. 3.2% sodium citrate was used as an anticoagulant. TAFIa/ai antigen was measured by ELISA method. TAFIa/ai antigen was identified in all samples of cord blood plasma. Its level was 91.50 ng/ml (range: 71.76 - 160.77 ng/ml vs. 55.46 ng/ml (range: 39.77 - 68.54 ng/ml in the mother's blood, which means that the level of TAFIa/ai antigen was significantly higher in fetal blood than in maternal blood (p<0.00001. TAFIa/ai antigen is an integral component of cord blood plasma. The concentration of TAFIa/ai antigen is about two times higher in fetal blood than in maternal blood.

  8. Recombinant coagulation factor VIIa labelled with the fac-99 mTc(CO)3-core: synthesis and in vitro evaluation of a putative new radiopharmaceutical for imaging in acute bleeding lesion

    DEFF Research Database (Denmark)

    Madsen, Jacob; Christensen, Jesper B.; Olsen, Ole H.

    2011-01-01

    Coagulation in blood is initiated when coagulation factor VII (FVII) binds to exposed TF and is activated to FVIIa, and the TF/ FVIIa complex may therefore provide a marker of vascular injury potentially applicable in diagnostic imaging of acute gastrointestinal (GI) bleeding. Methods: Recombinant...... yield and in 495% radiochemical purity. Pull down experiments showed that the biological activity (binding to tissue factor and to anti-FVII antibody) of the radiolabelled product remained intact in the formulation mixture as well as in human serum. By computer modeling analysis, two candidate sites...

  9. Effects of Blood Coagulate Removal Method on Aedes albopictus (Diptera: Culicidae) Life Table Characteristics and Vector Competence for Dengue Virus.

    Science.gov (United States)

    van Dodewaard, Caitlin A M; Richards, Stephanie L; Harris, Jonathan W

    2016-01-01

    Commercially available blood can be used as an alternative to live animals to maintain mosquito colonies and deliver infectious bloodmeals during research studies. We analyzed the extent to which two methods for blood coagulate removal (defibrination or addition of sodium citrate) affected life table characteristics (i.e., fecundity, fertility, hatch rate, and adult survival) and vector competence (infection, dissemination, and transmission) of Aedes albopictus (Skuse) for dengue virus (DENV). Two types of bovine blood were tested at two extrinsic incubation temperatures (27 or 30°C) for DENV-infected and uninfected mosquitoes. Fully engorged mosquitoes were transferred to individual cages containing an oviposition cup and a substrate. Eggs (fecundity) and hatched larvae (fertility) were counted. At 14 and 21 d post feeding on a DENV-infected bloodmeal, 15 mosquitoes were sampled from each group, and vector competence was analyzed (bodies [infection], legs [dissemination], and saliva [transmission]). Differences in life table characteristics and vector competence were analyzed for mosquitoes fed blood processed using different methods for removal of coagulates. The method for removal of coagulates significantly impacted fecundity, fertility, and hatch time in the uninfected group, but not DENV-infected group. Infected mosquitoes showed significantly higher fecundity and faster hatch time than uninfected mosquitoes. We show no significant differences in infection or dissemination rates between groups; however, horizontal transmission rate was significantly higher in mosquitoes fed DENV-infected citrated compared with defibrinated blood. We expect the findings of this study to inform research using artificial blood delivery methods to assess vector competence. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Sphingosine-1-Phosphate and Its Receptors: A Mutual Link between Blood Coagulation and Inflammation

    Directory of Open Access Journals (Sweden)

    Shailaja Mahajan-Thakur

    2015-01-01

    Full Text Available Sphingosine-1-phosphate (S1P is a versatile lipid signaling molecule and key regulator in vascular inflammation. S1P is secreted by platelets, monocytes, and vascular endothelial and smooth muscle cells. It binds specifically to a family of G-protein-coupled receptors, S1P receptors 1 to 5, resulting in downstream signaling and numerous cellular effects. S1P modulates cell proliferation and migration, and mediates proinflammatory responses and apoptosis. In the vascular barrier, S1P regulates permeability and endothelial reactions and recruitment of monocytes and may modulate atherosclerosis. Only recently has S1P emerged as a critical mediator which directly links the coagulation factor system to vascular inflammation. The multifunctional proteases thrombin and FXa regulate local S1P availability and interact with S1P signaling at multiple levels in various vascular cell types. Differential expression patterns and intracellular signaling pathways of each receptor enable S1P to exert its widespread functions. Although a vast amount of information is available about the functions of S1P and its receptors in the regulation of physiological and pathophysiological conditions, S1P-mediated mechanisms in the vasculature remain to be elucidated. This review summarizes recent findings regarding the role of S1P and its receptors in vascular wall and blood cells, which link the coagulation system to inflammatory responses in the vasculature.

  11. Laser speckle contrast imaging of skin blood perfusion responses induced by laser coagulation

    Energy Technology Data Exchange (ETDEWEB)

    Ogami, M; Kulkarni, R; Wang, H; Reif, R; Wang, R K [University of Washington, Department of Bioengineering, Seattle, Washington 98195 (United States)

    2014-08-31

    We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for highresolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing. (laser biophotonics)

  12. Laser speckle contrast imaging of skin blood perfusion responses induced by laser coagulation

    Science.gov (United States)

    Ogami, M.; Kulkarni, R.; Wang, H.; Reif, R.; Wang, R. K.

    2014-08-01

    We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for highresolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing.

  13. Relative effects of plasma, fibrinogen concentrate, and factor XIII on ROTEM coagulation profiles in an in vitro model of massive transfusion in trauma.

    Science.gov (United States)

    Schmidt, David E; Halmin, Märit; Wikman, Agneta; Östlund, Anders; Ågren, Anna

    2017-10-01

    Massive traumatic haemorrhage is aggravated through the development of trauma-induced coagulopathy, which is managed by plasma transfusion and/or fibrinogen concentrate administration. It is yet unclear whether these treatments are equally potent in ensuring adequate haemostasis, and whether additional factor XIII (FXIII) administration provides further benefits. In this study, we compared ROTEM whole blood coagulation profiles after experimental massive transfusion with different transfusion regimens in an in vitro model of dilution- and transfusion-related coagulopathy. Healthy donor blood was mixed 1 + 1 with six different transfusion regimens. Each regimen contained RBC, platelet concentrate, and either fresh frozen plasma (FFP) or Ringer's acetate (RA). The regimens were further augmented through addition of a low- or medium-dose fibrinogen concentrate and FXIII. Transfusion with FFP alone was insufficient to maintain tissue-factor activated clot strength, coincidental with a deficiency in fibrin-based clot strength. Fibrinogen concentrate conserved, but did not improve coagulation kinetics and overall clot strength. Only combination therapy with FFP and low-dose fibrinogen concentrate improved both coagulation kinetics and fibrin-based clot strength. Administration of FXIII did not result in an improvement of clot strength. In conclusion, combination therapy with both FFP and low-dose fibrinogen concentrate improved clotting time and produced firm clots, representing a possible preferred first-line regimen to manage trauma-induced coagulopathy when RBC and platelets are also transfused. Further research is required to identify optimal first-line transfusion fluids for massive traumatic haemorrhage.

  14. Factors contributing to the disturbance of coagulation and fibrinolysis in dengue virus infection

    Directory of Open Access Journals (Sweden)

    Yung-Chun Chuang

    2013-01-01

    Full Text Available Hemorrhage is one of the hallmarks of dengue hemorrhagic fever. However, the mechanisms that cause hemorrhage are unclear. In this review we focus on the possible factors that may be involved in the disturbance of coagulation and fibrinolysis during dengue virus (DENV infection. Factors such as autoantibodies and cytokines induced by DENV infection as well as hemostatic molecules expressed on DENV-infected cells, and DENV viral proteins may all contribute to the defect of hemostasis during DENV infection. It is the combination of these viral and host factors that may tilt the balance of coagulation and fibrinolysis toward bleeding in dengue patients.

  15. Characterization and pharmacological properties of a novel multifunctional Kunitz inhibitor from Erythrina velutina seeds.

    Directory of Open Access Journals (Sweden)

    Richele J A Machado

    Full Text Available Inhibitors of peptidases isolated from leguminous seeds have been studied for their pharmacological properties. The present study focused on purification, biochemical characterization and anti-inflammatory and anticoagulant evaluation of a novel Kunitz trypsin inhibitor from Erythrina velutina seeds (EvTI. Trypsin inhibitors were purified by ammonium sulfate (30-60%, fractionation followed by Trypsin-Sepharose affinity chromatography and reversed-phase high performance liquid chromatography. The purified inhibitor showed molecular mass of 19,210.48 Da. Furthermore, a second isoform with 19,228.16 Da was also observed. The inhibitor that showed highest trypsin specificity and enhanced recovery yield was named EvTI (P2 and was selected for further analysis. The EvTI peptide fragments, generated by trypsin and pepsin digestion, were further analyzed by MALDI-ToF-ToF mass spectrometry, allowing a partial primary structure elucidation. EvTI exhibited inhibitory activity against trypsin with IC50 of 2.2×10(-8 mol.L(-1 and constant inhibition (Ki of 1.0×10(-8 mol.L(-1, by a non-competitive mechanism. In addition to inhibit the activity of trypsin, EvTI also inhibited factor Xa and neutrophil elastase, but do not inhibit thrombin, chymotrypsin or peptidase 3. EvTI was investigated for its anti-inflammatory and anti-coagulant properties. Firstly, EvTI showed no cytotoxic effect on human peripheral blood cells. Nevertheless, the inhibitor was able to prolong the clotting time in a dose-dependent manner by using in vitro and in vivo models. Due to anti-inflammatory and anticoagulant EvTI properties, two sepsis models were here challenged. EvTI inhibited leukocyte migration and specifically acted by inhibiting TNF-α release and stimulating IFN-α and IL-12 synthesis. The data presented clearly contribute to a better understanding of the use of Kunitz inhibitors in sepsis as a bioactive agent capable of interfering in blood coagulation and inflammation.

  16. In vitro anti-thrombotic and anti-coagulant properties of blacklip abalone (Haliotis rubra) viscera hydrolysate.

    Science.gov (United States)

    Suleria, Hafiz Ansar Rasul; Masci, Paul P; Addepalli, Rama; Chen, Wei; Gobe, Glenda C; Osborne, Simone A

    2017-07-01

    Abalone viscera contain sulphated polysaccharides with anti-thrombotic and anti-coagulant activities. In this study, a hydrolysate was prepared from blacklip abalone (Haliotis rubra) viscera using papain and bromelain and fractionated using ion exchange and size exclusion chromatography. Hydrolysates and fractions were investigated for in vitro thrombin inhibition mediated through heparin cofactor II (HCII) as well as anti-coagulant activity in plasma and whole blood. On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited thrombin through HCII with an inhibitor concentration at 50% (IC50) of 16.5 μg/mL compared with 2.1 μg/mL for standard heparin. Fractionation concentrated HCII-mediated thrombin inhibition down to an IC50 of 1.8 μg/mL and improved anti-coagulant activities by significantly delaying clotting time. This study confirmed the presence of anti-thrombotic and anti-coagulant molecules in blacklip abalone viscera and demonstrated that these activities can be enriched with a simple chromatography regime. Blacklip abalone viscera warrant further investigation as a source of nutraceutical or functional food ingredients. Graphical abstract Schematic showing preparation of bioactive extracts and fractions from blacklip abalone.

  17. Tissue regenerating functions of coagulation factor XIII

    DEFF Research Database (Denmark)

    Soendergaard, C; Kvist, P H; Seidelin, J B

    2013-01-01

    The protransglutaminase factor XIII (FXIII) has recently gained interest within the field of tissue regeneration, as it has been found that FXIII significantly influences wound healing by exerting a multitude of functions. It supports haemostasis by enhancing platelet adhesion to damaged......-receptor 2 and the αVβ3 integrin is important for angiogenesis supporting formation of granulation tissue. Chronic inflammatory conditions involving bleeding and activation of the coagulation cascade have been shown to lead to reduced FXIII levels in plasma. Of particular importance for this review...

  18. Coagulation sensors based on magnetostrictive delay lines for biomedical and chemical engineering applications

    International Nuclear Information System (INIS)

    Maliaritsi, E.; Zoumpoulakis, L.; Simitzis, J.; Vassiliou, P.; Hristoforou, E.

    2006-01-01

    Coagulation sensors based on the magnetostrictive delay line technique are presented in this paper. They are based on magnetostrictive ribbons and are used for measuring the coagulation, curing or solidification time of different liquids. Experimental results indicate that the presented sensing elements can determine the blood coagulation with remarkable repeatability, thus allowing their use as blood coagulation sensors. Additionally, results indicate that they can also measure curing time of resins, solidification of fluids and coagulation of chemical substances, therefore allowing their implementation in chemical engineering applications

  19. Interactions of PLGA nanoparticles with blood components: protein adsorption, coagulation, activation of the complement system and hemolysis studies.

    Science.gov (United States)

    Fornaguera, Cristina; Calderó, Gabriela; Mitjans, Montserrat; Vinardell, Maria Pilar; Solans, Conxita; Vauthier, Christine

    2015-04-14

    The intravenous administration of poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been widely reported as a promising alternative for delivery of drugs to specific cells. However, studies on their interaction with diverse blood components using different techniques are still lacking. Therefore, in the present work, the interaction of PLGA nanoparticles with blood components was described using different complementary techniques. The influence of different encapsulated compounds/functionalizing agents on these interactions was also reported. It is worth noting that all these techniques can be simply performed, without the need for highly sophisticated apparatus or skills. Moreover, their transference to industries and application of quality control could be easily performed. Serum albumin was adsorbed onto all types of tested nanoparticles. The saturation concentration was dependent on the nanoparticle size. In contrast, fibrinogen aggregation was dependent on nanoparticle surface charge. The complement activation was also influenced by the nanoparticle functionalization; the presence of a functionalizing agent increased complement activation, while the addition of an encapsulated compound only caused a slight increase. None of the nanoparticles influenced the coagulation cascade at low concentrations. However, at high concentrations, cationized nanoparticles did activate the coagulation cascade. Interactions of nanoparticles with erythrocytes did not reveal any hemolysis. Interactions of PLGA nanoparticles with blood proteins depended both on the nanoparticle properties and the protein studied. Independent of their loading/surface functionalization, PLGA nanoparticles did not influence the coagulation cascade and did not induce hemolysis of erythrocytes; they could be defined as safe concerning induction of embolization and cell lysis.

  20. SGLT2 inhibitors: their potential reduction in blood pressure.

    Science.gov (United States)

    Maliha, George; Townsend, Raymond R

    2015-01-01

    The sodium glucose co-transporter 2 (SGLT2) inhibitors represent a promising treatment option for diabetes and its common comorbidity, hypertension. Emerging data suggests that the SGLT2 inhibitors provide a meaningful reduction in blood pressure, although the precise mechanism of the blood pressure drop remains incompletely elucidated. Based on current data, the blood pressure reduction is partially due to a combination of diuresis, nephron remodeling, reduction in arterial stiffness, and weight loss. While current trials are underway focusing on cardiovascular endpoints, the SGLT2 inhibitors present a novel treatment modality for diabetes and its associated hypertension as well as an opportunity to elucidate the pathophysiology of hypertension in diabetes. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  1. Epsilon aminocaproic acid reduces blood transfusion and improves the coagulation test after pediatric open-heart surgery: a meta-analysis of 5 clinical trials.

    Science.gov (United States)

    Lu, Jun; Meng, Haoyu; Meng, Zhaoyi; Sun, Ying; Pribis, John P; Zhu, Chunyan; Li, Quan

    2015-01-01

    Excessive postoperative blood loss after cardiopulmonary bypass is a common problem, especially in patients suffering from congenital heart diseases. The efficacy of epsilon aminocaproic acid (EACA) as a prophylactic treatment for postoperative bleeding after pediatric open-heart surgery has not been determined. This meta-analysis investigates the efficacy of EACA in the minimization of bleeding and blood transfusion and the maintenance of coagulation tests after pediatric open-heart surgery. A comprehensive literature search was performed to identify all randomized clinical trials on the subject. PubMed, Embase, the Cochrane Library, and the Chinese Medical Journal Network were screened. The primary outcome used for the analysis was postoperative blood loss. Secondary outcomes included postoperative blood transfusion, re-exploration rate and postoperative coagulation tests. The mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) were used as summary statistics. Five trials were included in this meta-analysis of 515 patients. Prophylactic EACA was associated with a reduction in postoperative blood loss, but this difference did not reach statistical significance (MD: -7.08; 95% CI: -16.11 to 1.95; P = 0.12). Patients treated with EACA received fewer postoperative blood transfusions, including packed red blood cells (MD: -8.36; 95% CI: -12.63 to -4.09; P = 0.0001), fresh frozen plasma (MD: -3.85; 95% CI: -5.63 to -2.08; P open-heart surgery. Prophylactic EACA minimizes postoperative blood transfusion and helps maintain coagulation in pediatric patients undergoing open-heart surgery. Therefore, the results of this study indicate that adjunctive EACA is a good choice for the prevention of postoperative blood transfusion following pediatric cardiac surgery.

  2. Coagulation of sheep intestinal and prefemoral lymph.

    Science.gov (United States)

    Hanley, C A; Johnston, M G; Nelson, W

    1988-06-01

    We have determined the most suitable method for the automated analysis of the clotting parameters in sheep intestinal and prefemoral lymph as defined by the Activated Partial Thromboplastin Times (APTT; measure of intrinsic coagulation pathway) and the Prothrombin Times (PT; measure of extrinsic coagulation pathway). As opposed to optical density systems, the use of a Fibro-System Fibrometer was found to provide the most consistent assessment of coagulation with the endpoint being the time to fibrin strand formation. We measured APTT in sheep intestinal and prefemoral lymph of 59.78 +/- 7.69 seconds and 51.03 +/- 10.49 seconds respectively. These values were more prolonged than those obtained from sheep blood plasma but only in the case of intestinal lymph were the differences significant (p less than 0.025). Human blood APTT values were significantly less than both sheep blood (p less than 0.05) and sheep intestinal (p less than 0.001) and prefemoral lymph (p less than 0.01). PT values were found to be 21.56 +/- 1.14 seconds in intestinal and 22.00 +/- 1.88 seconds in prefemoral lymph. These values were also significantly greater than those obtained from sheep blood (both p less than 0.001). Human blood PTs were significantly less than both sheep blood (p less than 0.001) and intestinal and prefemoral lymph (both p less than 0.001). Measurement of APTT and PT values in intestinal lymph and PT determinations in prefemoral lymph were not affected by storage in the refrigerator or freezer. There was some indication that APTT values in prefemoral samples were susceptible to storage artifacts; however, the differences in coagulation times were not significant.

  3. Production and properties of monoclonal antibodies to human blood coagulation factor VII and factor VIIa

    International Nuclear Information System (INIS)

    Mann, P.; Nesbitt, J.A.; Ge, M.; Kisiel, W.

    1986-01-01

    Human factor VII is a trace vitamin K-dependent protein that circulates in blood as a single-chain precursor to a serine protease. Upon activation, two-chain factor VIIa activates factor x in the presence of tissue factor and calcium. Purified preparations of single-chain (SC) human factor VII and two-chain (TC) factor VIIa were utilized to immunize Balb/c mice. Spleen cells from these immunized mice were fused to a non-secreting NS-1 derivative of X63-Ag8 myeloma cells and grown in selective medium. Analysis of culture supernatants by EIA revealed several hybridomas that were secreting IgG specific for Sc-factor VII and TC-factor VIIa. In addition, several hybridomas secreted IgG that reacted equally well with factor VII and factor VIIa. One of the latter McAb (A-29) reacted with the heavy chain of factor VIIa and the intact factor VII molecule equally as judged by Western blotting. A-29 was produced in ascites fluid, purified and coupled to activated CH-Sepharose. Application of one liter of normal human plasma to 10 ml of this immunoadsorbent column, elution of factor VII and subsequent Western blot using 125 I-rabbit anti-human factor VII indicated a single species of factor VII(M/sub r/ = 50 KDa) in normal plasma. These specific factor VII/VIIa McAbs may prove useful in the analysis of these factors, and in the separation of SC-factor VII from TC-factor VIIa

  4. Protein C inhibitor acts as a procoagulant by inhibiting the thrombomodulin-induced activation of protein C in human plasma

    NARCIS (Netherlands)

    Elisen, M. G.; von dem Borne, P. A.; Bouma, B. N.; Meijers, J. C.

    1998-01-01

    Protein C inhibitor (PCI), which was originally identified as an inhibitor of activated protein C, also efficiently inhibits coagulation factors such as factor Xa and thrombin. Recently it was found, using purified proteins, that the anticoagulant thrombin-thrombomodulin complex was also inhibited

  5. Serine protease inhibitors of parasitic helminths.

    Science.gov (United States)

    Molehin, Adebayo J; Gobert, Geoffrey N; McManus, Donald P

    2012-05-01

    Serine protease inhibitors (serpins) are a superfamily of structurally conserved proteins that inhibit serine proteases and play key physiological roles in numerous biological systems such as blood coagulation, complement activation and inflammation. A number of serpins have now been identified in parasitic helminths with putative involvement in immune regulation and in parasite survival through interference with the host immune response. This review describes the serpins and smapins (small serine protease inhibitors) that have been identified in Ascaris spp., Brugia malayi, Ancylostoma caninum Onchocerca volvulus, Haemonchus contortus, Trichinella spiralis, Trichostrongylus vitrinus, Anisakis simplex, Trichuris suis, Schistosoma spp., Clonorchis sinensis, Paragonimus westermani and Echinococcus spp. and discusses their possible biological functions, including roles in host-parasite interplay and their evolutionary relationships.

  6. Factors affecting the lung perfused blood volume in patients with intrapulmonary clots after anti-coagulation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Munemasa, E-mail: radokada@yamaguchi-u.ac.jp [Department of Radiology, Yamaguchi University Graduate School of Medicine 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Masuda, Yu [4th Grade of 6-year Medicine Doctor Program, Department of Medicine, Yamaguchi University Faculty of Medicine and Health Sciences 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Nakashima, Yoshiteru [Department of Radiology, Yamaguchi Grand Medical Center, Oosaki 77, Hofu, Yamaguchi 747-8511 (Japan); Nomura, Takafumi; Nakao, Sei [Department of Radiology, Yamaguchi University Graduate School of Medicine 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Suga, Kazuyoshi [Department of Radiology, St Hills Hospital, Imamurakita 3-7-18, Ube, Yamaguchi 755-0155 (Japan); Kido, Shoji [Computer-aided Diagnosis and Biomedical Imaging Research Biomedical Engineering, Applied Medical Engineering Science Graduate School of Medicine, Yamaguchi University, Tokiwadai 2-16-1, Ube, Yamaguchi 755-8611 (Japan); Matsunaga, Naofumi [Department of Radiology, Yamaguchi University Graduate School of Medicine 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan)

    2015-08-15

    Highlights: • Dual-energy CT can provide morphological and functional lung images in the same examination. • The subsequent dual-energy CT demonstrates the increased whole lung perfused blood volume (V{sub 120}) despite the residual intrapulmonary clots after treatment in one examination. • The increased whole lung perfusion (V{sub 120}) and a decreased low perfusion volume (V{sub 5}) result in the improvement in the low perfusion rate (%V{sub 5}) in the patients with acute pulmonary embolism after treatment. - Abstract: Objectives: Factors affecting the improvement in the lung perfused blood volume (LPBV) were evaluated based on the presence of intrapulmonary clots (IPCs) after anti-coagulation therapy using 64-slice dual-energy CT. Materials and methods: 96 patients exhibiting venous thromboembolism underwent initial and repeated LPBV examinations between December 2008 and July 2014. Fifteen patients were excluded due to pulmonary comorbidities, and a total of 81 patients were included in this study. Acute pulmonary embolism (PE) was diagnosed in 46 of the patients (56.7%). LPBV images were three-dimensionally reconstructed with two threshold ranges: 1–120 HU (V{sub 120}) and 1–5 HU (V{sub 5}), and the relative value of V{sub 5} per V{sub 120} expressed as %V{sub 5}. These values were subsequently compared with indicators of the severity of PE, such as the D-dimer level, heart rate and CT measurements. This study was approved by the local ethics committee. Results: In patients with IPCs, the D-dimer, V{sub 5} and %V{sub 5}values were significantly larger (p ≤ 0.01) in the initial LPBV, although these differences disappeared in subsequent LPBV after treatment. The right ventricular (RV) diameter, RV/left ventricular (RV/LV) diameter ratio and %V{sub 5} values were also significantly reduced, whereas the V{sub 5} value did not significantly decrease (p = 0.07), but V{sub 120} value significantly increased (p < 0.001) after treatment. However, in

  7. Inherited coagulation factor VII and X deficiencies associated with severe bleeding diathesis: Molecular genetics and pathophysiology

    NARCIS (Netherlands)

    Borensztajn, K.; Spek, C. A.

    2005-01-01

    The rare inherited coagulation disorders are a fascinating group of diseases that have provided us with important insights into the structure and functions of their respective deficient proteins. Factor (F)VII deficiency is the commonest of these inherited disorders of coagulation, whereas FX

  8. Changes of coagulation and fibrinolysis in middle-old aged patients with nonvalvular atrial fibrillation

    International Nuclear Information System (INIS)

    Li Xi; Xie Ying; Zhang Weijun; Zhao Ruixiang; Peng Xinjie; Zhang Wen; Zhang Yan; Cheng Xiuqin; Wang Longhua; Guo Yonghe; Zhou Yujie; Wen Shaojun; Liu Jielin

    2008-01-01

    Objective: To evaluate the changes of coagulation and fibrinolysis function in the middle-old aged patients with nonvalvular atrial fibrillation. Methods: The levels of D-Dimer and tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were detected in 92 middle-aged patients with nonvalvular atrial fibrillation (AF group) and 60 patients with sinus rhythm (control group) by immune turbidimetry and enzyme linked immunoadsorbent assay (ELISA). Univariate analysis was used to determine the differences between two groups, and covariance analysis was used to determine the factors which might affect coagulation and fibrinolysis indexes. Results: 1)The plasma levels of D-Dimer [(0.16±0.10) mg·L -1 ] and t-PA [(42.58± 30.28) μg·L -1 ] and PAI-1 [(86.03 ± 21.43) μg·L -1 ] in AF group were significantly higher than those in the control group [(0.10 ± 0.08) mg·L -1 , (26.02±13.84) μg·L -1 , (64.94±24.35) μg·L -1 ] (P<0.05 or P <0.001). The ratio of PAI-1/t-PA in AF group was higher than that in control group slightly. 2) After adjustment of the factors which included sex, age and plasma creatinine, uric acid, blood sugar, triglyceride and cholesterol, the levels of D-Dimer (P=0.047), t-PA (P=0.264) and PAI-1 (P=0.001) in AF group were higher than those in the control group. Conclusion: The middle-old aged patients with nonvalvular atrial fibrillation lose their balance of coagulation and fibrinolysis in the state of hypercoagulated and hypofibrinolysis. (authors)

  9. Response of Coagulation Indices to Two Types of Exercise of Eccentric and Isometric in Male Bodybuilding Athletes

    Directory of Open Access Journals (Sweden)

    Maryam Azimpour

    2016-05-01

    Full Text Available Abstract Background and Objectives: Although activation of blood coagulation system in response to physical activity has been identified to some extent, but the contribution of eccentric activity in comparison with isometric activity as resistance exercise, is not clear yet. Therefore, this research was carried out with the purpose of investigating the effect of one session of eccentric and isometric resistance exercise on some coagulation factors in male bodybuilders. Methods: In this semi-experimental study, 28 volunteers were randomly selected from male bodybuilders and divided into two experimental groups and one control group. One of the experimental groups performed eccentric exercise [controlled return (extension of the elbow flexion movement involving an eccentric contraction] and another group performed isometric exercises (holding barbell while flexing elbows at 45 degrees. In order to assess coagulation indices, blood sampling was performed 15 minutes before and immediately after the exercise. Results: Thromboplastin and prothrombin times did not significantly change immediately after the exercise, but the number of platelets significantly increased in both isometric and eccentric types of exercise immediately after the exercise. Conclusion: The results of isometric and eccentric acute resistance exercise showed that the exercise had no negative impact on blood coagulation factors, and increased coagulation system activity reflects the increased number of platelets. The difference between the results of researches carried out in this direction can be resulted from the difference between the exercise protocols, methods and measurement time, and level of preparedness of the participants in the research.

  10. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

    Science.gov (United States)

    Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

    2015-06-25

    Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

  11. Disseminated intravascular coagulation in solid tumors

    International Nuclear Information System (INIS)

    Terzieff, V.; Alonso, I.; Vázquez, A.

    2004-01-01

    It is estimated that 20-25% of cases of disseminated intravascular coagulation (DIC) relate to an underlying neoplasia primarily hematologic. It is estimated that about 5% of patients with solid tumors have CID clinic, although the incidence of subclinical alterations is much higher. The CID is not limited to the activation of the coagulation cascade, which leads to bleeding micro thrombosis and consumption of coagulation factors. Solid tumors are frequently associated adenocarcinomas producers mucin (especially gastric), usually in the context of a disseminated disease. The mucin may act as a promoter of the cascade, but probably it is a multi-event. High levels of TNF to produced by the tumor mass and chemotherapy-induced cell lysis have Also linked. Although the bleeding is usually oriented diagnosis, the most frequent cause of death is thrombosis. There are no specific tests for diagnosis. Elevated levels of D-dimer and products oriented fibrinogen degradation diagnosis. No reduction fibrinogen and almost always, one thrombocytopenia consumption. Treatment is complex and there is no consensus on many points. To recover the lost factors for consumption, it is recommended to use fresh frozen plasma and / or washed red blood cells. the heparin anticoagulation low dose is indicated since the disease causal can not be controlled quickly, but should not be initiated if there thrombocytopenia 50.000.El under profuse bleeding can require the use of tranexamic acid or EACA. Acute DIC, the case of our patient, is rare and very serious

  12. Factor Xa stimulates fibroblast procollagen production, proliferation, and calcium signaling via PAR1 activation

    International Nuclear Information System (INIS)

    Blanc-Brude, Olivier P.; Archer, Fabienne; Leoni, Patricia; Derian, Claudia; Bolsover, Steven; Laurent, Geoffrey J.; Chambers, Rachel C.

    2005-01-01

    Fibroblast proliferation and procollagen production are central features of tissue repair and fibrosis. In addition to its role in blood clotting, the coagulation cascade proteinase thrombin can contribute to tissue repair by stimulating fibroblasts via proteolytic activation of proteinase-activated receptor-1 (PAR 1 ). During hemostasis, the coagulation cascade proteinase factor X is converted into factor Xa. We have previously shown that factor Xa upregulates fibroblast proliferation via production of autocrine PDGF. In this study, we further examined the effects of factor Xa on fibroblast function and aimed to identify its signaling receptor. We showed that factor Xa stimulates procollagen promoter activity and protein production by human and mouse fibroblasts. This effect was independent of PDGF and thrombin production, but dependent on factor Xa proteolytic activity. We also showed that PAR 1 -deficient mouse fibroblasts did not upregulate procollagen production, mobilize cytosolic calcium, or proliferate in response to factor Xa. Desensitization techniques and PAR 1 -specific agonists and inhibitors were used to demonstrate that PAR 1 mediates factor Xa signaling in human fibroblasts. This is the first report that factor Xa stimulates extracellular matrix production. In contrast with endothelial cells and vascular smooth muscle cells, fibroblasts appear to be the only cell type in which the effects of factor Xa are mediated mainly via PAR 1 and not PAR 2 . These findings are critical for our understanding of tissue repair and fibrotic mechanisms, and for the design of novel approaches to inhibit the profibrotic effects of the coagulation cascade without compromising blood hemostasis

  13. Effects of anti-aggregant, anti-inflammatory and anti-coagulant drug consumption on the preparation and therapeutic potential of plasma rich in growth factors (PRGF).

    Science.gov (United States)

    Anitua, Eduardo; Troya, María; Zalduendo, Mar; Orive, Gorka

    2015-02-01

    The prevalence and incidence of trauma-related injuries, coronary heart disease and other chronic diseases increase dramatically with age. This population sector is therefore a regular consumer of different types of drugs that may affect platelet aggregation and the coagulation cascade. We have evaluated whether the consumption of acetylsalicylic acid, acenocoumarol, glucosamine sulfate and chondroitin sulfate, and therefore their presence in blood, could interfere with the preparation and biological outcomes of plasma rich in growth factors (PRGF). Clotting time, clot retraction and platelet activation of PRGF was evaluated. PRGF growth factor content and the release of different biomolecules by tendon fibroblasts were also quantified, as well as cell proliferation and cell migration. The preparation and biological potential of PRGF is not affected by the intake of the evaluated drugs, and solely its angiogenic potential and its capacity to induce HA and fibronectin synthesis, is reduced in patients taking anti-coagulants.

  14. Feasibility and Safety of Local Treatment with Recombinant Human Tissue Factor Pathway Inhibitor in a Rat Model of Streptococcus pneumoniae Pneumonia.

    Directory of Open Access Journals (Sweden)

    Florry E van den Boogaard

    Full Text Available Pulmonary coagulopathy is intrinsic to pulmonary injury including pneumonia. Anticoagulant strategies could benefit patients with pneumonia, but systemic administration of anticoagulant agents may lead to suboptimal local levels and may cause systemic hemorrhage. We hypothesized nebulization to provide a safer and more effective route for local administration of anticoagulants. Therefore, we aimed to examine feasibility and safety of nebulization of recombinant human tissue factor pathway inhibitor (rh-TFPI in a well-established rat model of Streptococcus (S. pneumoniae pneumonia. Thirty minutes before and every 6 hours after intratracheal instillation of S. pneumonia causing pneumonia, rats were subjected to local treatment with rh-TFPI or placebo, and sacrificed after 42 hours. Pneumonia was associated with local as well as systemic activation of coagulation. Nebulization of rh-TFPI resulted in high levels of rh-TFPI in bronchoalveolar lavage fluid, which was accompanied by an attenuation of pulmonary coagulation. Systemic rh-TFPI levels remained undetectable, and systemic TFPI activity and systemic coagulation were not affected. Histopathology revealed no bleeding in the lungs. We conclude that nebulization of rh-TFPI seems feasible and safe; local anticoagulant treatment with rh-TFPI attenuates pulmonary coagulation, while not affecting systemic coagulation in a rat model of S. pneumoniae pneumonia.

  15. Cloning of cDNAs coding for the heavy chain region and connecting region of human factor V, a blood coagulation factor with four types of internal repeats

    International Nuclear Information System (INIS)

    Kane, W.H.; Ichinose, A.; Hagen, F.S.; Davie, E.W.

    1987-01-01

    Human factor V is a high molecular weight plasma glycoprotein that participates as a cofactor in the conversion of prothrombin to thrombin by factor X/sub a/. Prior to its participation in the coagulation cascade, factor V is converted to factor V/sub a/ by thrombin generating a heavy chain and a light chain, and these two chains are held together by calcium ions. A connecting region originally located between the heavy and light chains is liberated during the activation reaction. In a previous study, a cDNA of 2970 nucleotides that codes for the carboxyl-terminal 938 amino acids of factor V was isolated and characterized from a Hep G2 cDNA library. This cDNA has been used to obtain additional clones from Hep G2 and human liver cDNA libraries. Furthermore, a Hep G2 cDNA library prepared with an oligonucleotide from the 5' end of these cDNAs was screened to obtain overlapping cDNA clones that code for the amino-terminal region of the molecule. The composite sequence of these clones spans 6911 nucleotides and is consistent with the size of the factor V message present in Hep G2 cells (approximately 7 kilobases). The cDNA codes for a leader sequence of 28 amino acids and a mature protein of 2196 amino acids. The amino acid sequence predicted from the cDNA was in complete agreement with 139 amino acid residues that were identified by Edman degradation of cyanogen bromide peptides isolated from the heavy chain region and connecting region of plasma factor V. The domain structure of human factor V is similar to that previously reported for human coagulation factor VIII. Two types of tandem repeats (17 and 9 amino acids) have also been identified in the connecting region of factor V. The present data indicate that the amino acid sequence in the heavy and light chain regions of factor V is ∼ 40% identical with the corresponding regions of factor VIII

  16. Acquired factor VIII inhibitor syndrome: A rare cause of hematuria

    Directory of Open Access Journals (Sweden)

    Muthuvel Seral Kannan

    2015-01-01

    Full Text Available A 50-year-old woman presented with gross hematuria for 1 month. Clinical examinations, laboratory investigations, ultrasound and contrast computed tomography were normal, except anemia. Cystoscopy revealed bloody efflux from the right side. Retrograde pyelogram showed filling defect in the renal pelvis and biopsy was inconclusive. Renal angiogram was normal. She developed ecchymosis on the right thigh and arm with elevated activated partial thromboplastin time. The partial thromboplastin time correction study and Bethesda study confirmed the presence of acquired factor VIII inhibitor (acquired hemophilia. With flexible ureterorenoscopy, the mass in the renal pelvis was removed and its histopathology revealed clotted blood. The patient was subsequently managed with steroids and Factor eight inhibitor bypass activity.

  17. Removal of Dye in Wastewater by Adsorption-Coagulation Combined System with Hibiscus sabdariffa as the Coagulant

    Directory of Open Access Journals (Sweden)

    Hoong Ho Nicholas Jian

    2018-01-01

    Full Text Available The conventional process to treat dye wastewater is the physicochemical treatment such as coagulation, flocculation and adsorption process. A new approach has been demonstrated to treat Congo red dye wastewater, which is the adsorption-coagulation hybrid process. Natural coagulant extracted from Hibiscus sabdariffa seeds is used as the coagulant while activated carbon is used as the adsorbent in this case study. The objective of this experiment is to study the significant factors that will affect the efficiency of dye removal. Then, the optimum conditions for the hybrid process is determined using Respond Surface Methodology (RSM. The variables are pH, initial dye concentration, coagulant dosage and adsorbent dosage while the response of experiment is the dye removal percentage. A three-level and four-variable Box-Behnken design (BBD is used for the RSM. A total of 27 sets of experimental results is required to determine the optimum conditions. Jar test is used to conduct the experiment with the addition of coagulant and adsorbent simultaneously. Based on the regression model analysis and ANOVA, the highly significant factors that contribute to the dye removal efficiency through adsorption-coagulation hybrid process are pH of solution and initial dye concentration. The RSM results shows that the optimised process parameters for adsorption-coagulation hybrid process with Hibiscus sabdariffa seeds as the coagulant and activated carbon as the adsorbent are pH 2, initial dye concentration of 385 ppm, coagulant dosage of 209 mg/L and adsorbent dosage of 150 mg/L. The dye removal reaches up to 96.67% under optimum parameters.

  18. Contribution of a portable air plasma torch to rapid blood coagulation as a method of preventing bleeding

    International Nuclear Information System (INIS)

    Kuo, S P; Chen, C Y; Fan, H W; Tarasenko, O; Scott, A; Lahiani, M; Alusta, P; Chang, J; Popovic, S; Drake, J D; Nikolic, M

    2009-01-01

    The effectiveness and mechanism of a low temperature air plasma torch in clotting blood are explored. Both blood droplets and smeared blood samples were used in the tests. The treated droplet samples reveal how blood clotting depends on the distance at which the torch operated, and for how long the droplets have been exposed to the torch. Microscopy and cell count of smeared blood samples shed light on dependencies of erythrocyte and platelet counts on torch distance and exposure time. With an increase of torch distance, the platelet count of treated blood samples increases but is less than that of the control. The flux of reactive atomic oxygen (RAO) and the degree of blood clotting decreased. With an increase of exposure time, platelet count of treated samples decreased, while the degree of clot increased. The correlation among these dependencies and published data support a blood clotting mechanism that RAO as well as other likely reactive oxygen species generated by the plasma torch activate erythrocyte-platelets interactions and induces blood coagulation.

  19. Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease

    Science.gov (United States)

    Uderhardt, Stefan; Ackermann, Jochen A.; Fillep, Tobias; Hammond, Victoria J.; Willeit, Johann; Stark, Konstantin; Rossaint, Jan; Schubert, Irene; Mielenz, Dirk; Dietel, Barbara; Raaz-Schrauder, Dorette; Ay, Cihan; Thaler, Johannes; Heim, Christian; Collins, Peter W.; Schabbauer, Gernot; Mackman, Nigel; Voehringer, David; Nadler, Jerry L.; Lee, James J.; Massberg, Steffen; Rauh, Manfred; O’Donnell, Valerie B.

    2017-01-01

    Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase–derived hydroxyeicosatetraenoic acid–phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease. PMID:28566277

  20. Pathophysiological significance and therapeutic applications of snake venom protease inhibitors.

    Science.gov (United States)

    Thakur, Rupamoni; Mukherjee, Ashis K

    2017-06-01

    Protease inhibitors are important constituents of snake venom and play important roles in the pathophysiology of snakebite. Recently, research on snake venom protease inhibitors has provided valuable information to decipher the molecular details of various biological processes and offer insight for the development of some therapeutically important molecules from snake venom. The process of blood coagulation and fibrinolysis, in addition to affecting platelet function, are well known as the major targets of several snake venom protease inhibitors. This review summarizes the structure-functional aspects of snake venom protease inhibitors that have been described to date. Because diverse biological functions have been demonstrated by protease inhibitors, a comparative overview of their pharmacological and pathophysiological properties is also highlighted. In addition, since most snake venom protease inhibitors are non-toxic on their own, this review evaluates the different roles of individual protease inhibitors that could lead to the identification of drug candidates and diagnostic molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Thrombin and factor Xa link the coagulation system with liver fibrosis.

    Science.gov (United States)

    Dhar, Ameet; Sadiq, Fouzia; Anstee, Quentin M; Levene, Adam P; Goldin, Robert D; Thursz, Mark R

    2018-05-08

    Thrombin activates hepatic stellate cells via protease-activated receptor-1. The role of Factor Xa (FXa) in hepatic fibrosis has not been elucidated. We aimed to evaluate the impact of FXa and thrombin in vitro on stellate cells and their respective inhibition in vivo using a rodent model of hepatic fibrosis. HSC-LX2 cells were incubated with FXa and/or thrombin in cell culture, stained for αSMA and relative gene expression and gel contraction calculated. C57BL/6 J mice were administered thioacetamide (TAA) for 8 weeks with Rivaroxaban (n = 15) or Dabigatran (n = 15). Control animals received TAA alone (n = 15). Fibrosis was scored and quantified using digital image analysis and hepatic tissue hydroxyproline estimated. Stellate cells treated with FXa and thrombin demonstrated upregulation of procollagen, TGF-beta, αSMA and significant cell contraction (43.48%+/- 4.12) compared to culturing with FXa or thrombin alone (26.90%+/- 8.90, p = 0.02; 13.1%+/- 9.84, p < 0.001). Mean fibrosis score, percentage area of fibrosis and hepatic hydroxyproline content (2.46 vs 4.08, p = 0.008; 2.02% vs 3.76%, p = 0.012; 276.0 vs 651.3, p = 0.0001) were significantly reduced in mice treated with the FXa inhibitor compared to control mice. FXa inhibition was significantly more effective than thrombin inhibition in reducing percentage area of fibrosis and hepatic hydroxyproline content (2.02% vs 3.70%,p = 0.031; 276.0 vs 413.1,p = 0.001). FXa promotes stellate cell contractility and activation. Early inhibition of coagulation using a FXa inhibitor significantly reduces TAA induced murine liver fibrosis and may be a viable treatment for liver fibrosis in patients.

  2. Metabolism and toxicity of therapeutic chelating agents Pt. 15. Effect of Ca-DTPA and Zn-DTPA on blood coagulation

    Energy Technology Data Exchange (ETDEWEB)

    Lohbreier, J [Kernforschungszentrum Karlsruhe (Germany, F.R.). Inst. fuer Genetik und fuer Toxikologie von Spaltstoffen

    1977-10-01

    Single subcutaneous injection of Ca-DTPA by a toxic dosage results in rats in a short-term moderate reduction of the plasma concentration of factors belonging to the endogenous coagulation system and of the prothrombin complex. Neither the temporary fibrinolysis nor the thrombocytopenia occurring later deeply affect coagulation as a whole. By fractionation of the daily dose or by continuous infusion of Ca-DTPA-damage to the plasmatic coagulation system is not further increased, although the intensity of thrombocytopenia is enhanced which is minimum after a single administration of the chelate. The platelet functions, on the other hand, are not influenced by Ca-DTPA. The much better compatibility of Zn-DTPA as compared to Ca-DTPA was fully confirmed also with respect to the hematological and coagulation parameters.

  3. Effect of red wine and red grape extract on blood lipids, haemostatic factors, and other risk factors for cardiovascular disease

    DEFF Research Database (Denmark)

    Hansen, Alice Schmidt; Marckmann, P.; Dragsted, L.O.

    2005-01-01

    . Plasma high-density lipoprotein (HDL)- cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol (LDL-C), HDL-C/LDL-C-ratio, very-low-density lipoprotein ( VLDL)- triacylglycerol, total cholesterol, fibrinogen, factor VII coagulant activity (FVIIc), blood pressure, and body weight were determined......-triacylglycerol, total cholesterol, FVIIc, or blood pressure. Drinking wine was associated with relative body weight increments closely corresponding to the energy contributed by the alcohol component. Conclusion: Moderate red wine consumption for 4 weeks is associated with desirable changes in HDL-C and fibrinogen......Objective: Some epidemiological studies found a lower risk of cardiovascular disease among wine drinkers than among drinkers of other types of ethanol. This difference might be due to an effect of nonalcohol compounds in wine on important cardiovascular risk factors. The objective of this study...

  4. Quantitative evaluation of plasma after methylene blue and white light treatment in four Chinese blood centers.

    Science.gov (United States)

    Chunhui, Yang; Guohui, Bian; Hong, Yang; Xiaopu, Xiao; Zherong, Bai; Mingyuan, Wang; Xinsheng, Zhang; Juanjuan, Wang; Changqing, Li; Wuping, Li

    2013-12-01

    Pathogen reduction technology is an important process in the blood safety system, including solvent/detergent treatment, filtration and methylene blue-photochemical technology (MB-PCT). To investigate the quality of MB-PCT-treated plasma, plasma samples from four Chinese blood centers were analyzed over 12 months of storage to determine the recovery of activities and levels of various plasma proteins. Ten plasma units each from the Suzhou, Yancheng, Chongqing and Shandong blood centers were divided into two aliquots. One was subjected to treatment with one of two methylene blue-photochemical technology instruments and the other was used as control. The treated and untreated sample pairs were stored at -30°C. The recovery rates of coagulation factors, inhibitor proteins, total protein, immunoglobulins, and complement proteins were measured at different time points after storage. The mean recovery of most proteins exceeded 80% after MB treatment. The exceptions were factor XI and fibrinogen, of which only 71.3-74% and 69.0-92.3% were retained during storage. The two equipment types differed in terms of residual MB concentration in the plasma samples (0.18 μM and 0.29 μM, respectively). They had similar protein recovery rates at 0.5 month but differed at later time points. The four blood centers differed significantly with regard to factor II, V, VIII and fibrinogen activities. Only the samples from the Shandong blood center met the methylene blue treated fresh frozen plasma requirement. The major factor that influenced the quality of the MB-FFP samples was the time taken between blood collection and storage. Methylene blue treated plasma showed reduced coagulation factor (CF) activity and protein levels. The MB treatment-induced damage to the proteins was acceptable at the four Chinese blood centers, but the quality of the MB-treated plasma in general was not satisfactory. The main factor affecting plasma quality may be the duration of the collection and

  5. Evaluation of Consequences of Dust Positioned in Southwest of Iran on Coagulant Factors

    Science.gov (United States)

    Saeb, Keivan; Sarizade, Gholamreza; Khodadi, Mohammad; Biazar, Esmaeil

    2013-01-01

    Background: Various regions in Iran, especially the Khuzestan Province, have been covered by dust and dirt during the past two years due to environmental changes in the Middle East. We sought to evaluate the effect of these pollutants on the coagulant factors of people residing in Abadan and Khoramshahr, two major cities of Khuzestan Province. Methods: One hundred twenty-nine healthy individuals were enrolled into this study, and their prothrombin time as well as fibrinogen, platelet, and Factor VIII levels were measured before and after climate changes. Results: After climate changes, the mean prothrombin time decreased, while the fibrinogen, platelet, and Factor VIII levels rose. Conclusion: The results of this study suggest that the pollutants deployed in the Middle East can affect prothrombin time as well as fibrinogen, platelet, and Factor VII levels considerably and increase coagulant state. The pollutants can, consequently, increase the risk of cardiovascular diseases. It seems that cooperation at government levels between Iran and its neighboring countries is required to reverse desertification and avoid inaccurate usage of subterranean water resources so as to lessen air pollution. PMID:23825886

  6. Predictive factors for beneficial application of high-frequency electromagnetics for tumour vaporization and coagulation in neurosurgery

    Directory of Open Access Journals (Sweden)

    Koerbel Andrei

    2008-04-01

    Full Text Available Abstract Objective To identify preoperative and intraoperative factors and conditions that predicts the beneficial application of a high-frequency electromagnetic field (EMF system for tumor vaporization and coagulation. Methods One hundred three subsequent patients with brain tumors were microsurgically treated using the EMF system in addition to the standard neurosurgical instrumentarium. A multivariate analysis was performed regarding the usefulness (ineffective/useful/very helpful/essential of the new technology for tumor vaporization and coagulation, with respect to tumor histology and location, tissue consistency and texture, patients' age and sex. Results The EMF system could be used effectively during tumor surgery in 83 cases with an essential contribution to the overall success in 14 cases. In the advanced category of effectiveness (very helpful/essential, there was a significant difference between hard and soft tissue consistency (50 of 66 cases vs. 3 of 37 cases. The coagulation function worked well (very helpful/essential for surface (73 of 103 cases and spot (46 of 103 cases coagulation when vessels with a diameter of less than one millimeter were involved. The light-weight bayonet hand piece and long malleable electrodes made the system especially suited for the resection of deep-seated lesions (34 of 52 cases compared to superficial tumors (19 of 50 cases. The EMF system was less effective than traditional electrosurgical devices in reducing soft glial tumors. Standard methods where also required for coagulation of larger vessels. Conclusion It is possible to identify factors and conditions that predict a beneficial application of high-frequency electromagnetics for tumor vaporization and coagulation. This allows focusing the use of this technology on selective indications.

  7. COAGULATION ACTIVITY IN LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    Dr. Sheikh Sajjadieh Mohammad Reza

    2009-07-01

    Full Text Available Patients with advanced hepatic failure may present with the entire spectrum of coagulation factor deficiencies. This study was designed to determine laboratory abnormalities in coagulation in chronic liver disease and the association of these abnormalities with the extent of chronic hepatitis and cirrhosis. Coagulation markers were assayed in 60 participants: 20 patients with chronic hepatitis, 20 patients with cirrhosis, and 20 healthy individuals (control. Plasma levels of anti-thrombin III were determined by a chromogenic substrate method, and plasma concentrations of fibrinogen were analyzed by the Rutberg method. Commercially available assays were used for laboratory coagulation tests. The levels of coagualation activity markers in patients with chronic liver disease were significantly different in comparison to those in healthy participants. These results indicate the utility of measuring markers for coagulation activity in determining which cirrhosis patients are more susceptible to disseminated intravascular coagulation.

  8. Coagulation parameters as a guide for fresh frozen plasma transfusion practice: A tertiary hospital experience

    Directory of Open Access Journals (Sweden)

    Wan Haslindawani W

    2010-01-01

    Full Text Available Introduction: The appropriate use of blood and blood products means the transfusion of safe blood products only to treat a condition leading to significant morbidity or mortality, which cannot be prevented or managed effectively by other means. The safety and effectiveness of transfusion depend on the appropriate clinical use of blood and blood products. This study was conducted to review the practice of fresh frozen plasma usage (FFP for transfusion, based on the coagulation profile, requested by various departments in the Hospital Universiti Sains Malaysia (HUSM. Methodology: A retrospective review of blood bank records and coagulation profile results of the patients given FFP from October to December 2006, in Hospital USM was undertaken. The criteria set by the College of American Pathologists in 1994, were used as the guidelines. Results: One thousand six hundred and ninety-eight units of FFP were used during this study period. Only 806 (47.47% FFP units were deemed appropriate. 20.38% were based on studies without any coagulation tests prior to transfusion and 21.13% were transfused for mild prolongation of coagulation test results. About 6.41% requested FFP in the setting of normal coagulation results. Conclusion: Our results showed that a significant proportion of the FFP transfusion was not guided by the coagulation profile. We recommend that a continuous education on FFP transfusion may help to guide the appropriate request for FFP.

  9. Structural and functional studies on human coagulation factor V

    OpenAIRE

    Neut Kolfschoten, Marijn van der

    2005-01-01

    The aim of this research was to obtain a better insight into the structure and functioning of clotting factor V (FV), a protein that plays an important role in the regulation of clotting. Congenital defects in FV can greatly disturb the coagulation system, and can lead to symptoms ranging from para-haemophilia to thrombosis. One example of a congenital defect in FV I is the R506Q mutation (an aminoacid change at position 506 in the aminoacid chain of FV). This deviating FV molecule (also know...

  10. Serum Proteome Signature of Radiation Response: Upregulation of Inflammation-Related Factors and Downregulation of Apolipoproteins and Coagulation Factors in Cancer Patients Treated With Radiation Therapy—A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Widlak, Piotr, E-mail: widlak@io.gliwice.pl [Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice (Poland); Jelonek, Karol; Wojakowska, Anna; Pietrowska, Monika [Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice (Poland); Polanska, Joanna [Institute of Automatics Control, Silesian University of Technology, Gliwice (Poland); Marczak, Łukasz [Institute of Bioorganic Chemistry of the Polish Academy of Sciences, Poznan (Poland); Miszczyk, Leszek; Składowski, Krzysztof [Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice (Poland)

    2015-08-01

    features of serum proteome. The signature included upregulation of factors involved in acute or inflammatory response but also downregulation of plasma apolipoproteins and factors involved in blood coagulation.

  11. Biomaterials trigger endothelial cell activation when co-incubated with human whole blood.

    Science.gov (United States)

    Herklotz, Manuela; Hanke, Jasmin; Hänsel, Stefanie; Drichel, Juliane; Marx, Monique; Maitz, Manfred F; Werner, Carsten

    2016-10-01

    Endothelial cell activation resulting from biomaterial contact or biomaterial-induced blood activation may in turn also affect hemostasis and inflammatory processes in the blood. Current in vitro hemocompatibility assays typically ignore these modulating effects of the endothelium. This study describes a co-incubation system of human whole blood, biomaterial and endothelial cells (ECs) that was developed to overcome this limitation. First, human endothelial cells were characterized in terms of their expression of coagulation- and inflammation-relevant markers in response to various activators. Subsequently, their capacity to regulate hemostasis as well as complement and granulocyte activation was monitored in a hemocompatibility assay. After blood contact, quiescent ECs exhibited anticoagulant and anti-inflammatory properties. When they were co-incubated with surfaces exhibiting pro-coagulant or pro-inflammatory characteristics, the ECs down-regulated coagulation but not complement or leukocyte activation. Analysis of intracellular levels of the endothelial activation markers E-selectin and tissue factor showed that co-incubation with model surfaces and blood significantly increased the activation state of ECs. Finally, the coagulation- and inflammation-modulating properties of the ECs were tested after blood/biomaterial exposure. Pre-activation of ECs by biomaterials in the blood induced a pro-coagulant and pro-inflammatory state of the ECs, wherein the pro-coagulant response was higher for biomaterial/blood pre-activated ECs than for TNF-α-pre-activated cells. This work provides evidence that biomaterials, even without directly contacting the endothelium, affect the endothelial activation state with and have consequences for plasmatic and cellular reactions in the blood. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. An updated concept of coagulation with clinical implications.

    Science.gov (United States)

    Romney, Gregory; Glick, Michael

    2009-05-01

    Over the past century, a series of models have been put forth to explain the coagulation mechanism. The coagulation cascade/waterfall model has gained the most widespread acceptance. This model, however, has problems when it is used in different clinical scenarios. A more recently proposed cell-based model better describes the coagulation process in vivo and provides oral health care professionals (OHCPs) with a better understanding of the clinical implications of providing dental care to patients with potentially increased bleeding tendencies. The authors conducted a literature search using the PubMed database. They searched for key words including "coagulation," "hemostasis," "bleeding," "coagulation factors," "models," "prothrombin time," "activated partial thromboplastin time," "international normalized ratio," "anticoagulation therapy" and "hemophilia" separately and in combination. The coagulation cascade/waterfall model is insufficient to explain coagulation in vivo, predict a patient's bleeding tendency, or correlate clinical outcomes with specific laboratory screening tests such as prothrombin time, activated partial thromboplastin time and international normalized ratio. However, the cell-based model of coagulation that reflects the in vivo process of coagulation provides insight into the clinical ramifications of treating dental patients with specific coagulation factor deficiencies. Understanding the in vivo coagulation process will help OHCPs better predict a patient's bleeding tendency. In addition, applying the theoretical concept of the cell-based model of coagulation to commonly used laboratory screening tests for coagulation and bleeding will result in safer and more appropriate dental care.

  13. Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies.

    Science.gov (United States)

    Suleria, Hafiz Ansar Rasul; Masci, Paul P; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A; Gobe, Glenda C

    2017-08-04

    Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic.

  14. The influence of prophylactic factor VIII in severe hemophilia A

    Science.gov (United States)

    Gissel, Matthew; Whelihan, Matthew F; Ferris, Lauren A; Mann, Kenneth G; Rivard, Georges E; Brummel-Ziedins, Kathleen E

    2013-01-01

    Introduction Hemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Aim To evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe hemophilia utilizing both empirical and computational models. Methods We investigated twenty-five clinically severe hemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. Results Due to prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from hemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk. PMID:21899664

  15. Plasma triacylglycerol and coagulation factor concentrations predict the anticoagulant effect of dietary fish oil in overweight subjects

    DEFF Research Database (Denmark)

    Vanschoonbeek, Kristof; Feijge, Marion A H; Saris, Wim H M

    2007-01-01

    fish-oil effects. In study 1, 54 overweight subjects consumed 3.1 g (n-3) PUFA daily. In study 2, which involved 42 overweight patients with type 2 diabetes, 20 subjects consumed (n-3) PUFA, whereas 22 others ingested a preparation rich in (n-6) PUFA. Tissue factor-induced thrombin generation (thrombin...... potential) was determined as an integrated measure of plasma coagulant activity. In both studies, multivariate analysis indicated a strong clustering of fasting concentrations of triacylglycerols, prothrombin, factor V, factor VII, and factor X with one another at baseline. This cluster of factors......-induced lowering of triacylglycerol and coagulation factor V, VII, and X concentrations, and thrombin generation. We conclude that high fasting triacylglycerol concentrations predict high procoagulant activity and a lowering of thrombin potential with dietary fish oil....

  16. Early Blood Transfusion and Resolution of Disseminated Intravascular Coagulation Associated with Massive Subgaleal Hemorrhage.

    Science.gov (United States)

    Modanlou, Houchang; Hutson, Shandee; Merritt, Allan Thurman

    2016-01-01

    A male infant delivered to a primipara woman following vacuum applications. He was vigorous at birth, with small caput and scalp bruising. His head was enlarging; he became pale with respiratory distress. Subgaleal hemorrhage (SGH) was suspected. His hematocrit was noted to be 26.2 percent prior to transfusion of O, Rh-negative blood (40 mL/kg). Moderate disseminated intravascular coagulation (DIC) was noted at 12 hours of age. Posttransfusion of fresh frozen plasma (FFP), his condition became stable, and DIC gradually resolved. Head magnetic resonance imaging did not show intracranial hemorrhage. Although one episode of seizures was noted, electroencephalogram was normal. With the application of obstetric vacuum, we recommend that the neonatal health care professionals frequently evaluate the infant's condition. In light of developing fluctuant subgaleal fluid associated with pallor, anemia, metabolic acidosis, and respiratory distress, immediate blood transfusion is warranted. In the presence of DIC, transfusion of FFP is beneficial.

  17. Characterization and blood coagulation evaluation of the water-soluble chitooligosaccharides prepared by a facile fractionation method.

    Science.gov (United States)

    Lin, Chia-Wen; Lin, Jui-Che

    2003-01-01

    Water-soluble chitooligosaccharides have been reported to have specific biological activities. In this study, the chitosan samples with different degree of acetylation were used separately to prepare chitooligosaccharide (COS) and highly deacetylated chitooligosaccharide (HDCOS) through the nitrous acid depolymerization. Rather than using the conventional fractionation schemes commonly employed, such as dialysis and ultrafiltration which require a large amount of deionized water as well as a fair long dwell time, an unique fractionation scheme is explored to recover and desalt these nitrous-acid depolymerized chitosan with different molecular weights. This fractionation scheme is based on the differential solubility variation of depolymerized products within the aqueous solutions that contain various ratios of methanol. It was noted that chitosan with different molecular weight can be successfully recovered and fractionated with methanol added sequentially up to a volume of four times of original depolmerized product. In addition, chemical characterization of the fractionated water-soluble COS and HDCOS by 1H NMR spectroscopy and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) indicated that the chitosan depolymerization reaction is greatly influenced by the degree of acetylation of the parental chitosan reactant. Moreover, the modified whole blood clotting time assay and the platelet coagulation test suggested that the 1:2 fractionated water-soluble COS and HDCOS obtained are much less procoagulant than their parental chitosan compound and can be of use in biomedical applications in which blood coagulation is not desired.

  18. Coagulation profile in open and video-assisted thoracoscopic lobectomies

    DEFF Research Database (Denmark)

    Christensen, Thomas Decker; Vad, Henrik; Pedersen, Søren

    2018-01-01

    OBJECTIVES: Lung cancer patients are perceived to have a relatively high risk of venous thromboembolic events due to an activation of the coagulation system. In terms of activation of the coagulation system, the difference between video-assisted thoracoscopic surgery (VATS) and open lobectomies...... for primary lung cancer has not been investigated. The aim of this study was to compare the impact on the coagulation system in patients undergoing curative surgery for primary lung cancer by either VATS or open lobectomies. METHODS: In total, 62 patients diagnosed with primary lung cancer were allocated...... to either VATS (n = 32) or open lobectomies (n = 30). All patients received subcutaneous injections with dalteparin (Fragmin®) 5000 IE once daily. The coagulation was assessed pre- and intraoperatively, and the first 2 days postoperatively by standard coagulation blood tests, thromboelastometry (ROTEM...

  19. Joint bleeds increase the inhibitor response to human factor VIII in a rat model of severe haemophilia A

    DEFF Research Database (Denmark)

    Löfgren, Karin Maria; Søndergaard, H.; Skov, Søren

    2016-01-01

    Introduction The most serious complication in haemophilia A (HA) replacement therapy with coagulation factor VIII (FVIII) is neutralizing antibodies, i.e. inhibitors. It has been hypothesized that danger signals generated during a bleed might have an adjuvant effect on the immune response to FVIII...... in on-demand treatment, increasing the inhibitor risk. Aim To compare the antibody response to treatment with recombinant human FVIII (rhFVIII) in relation to induced knee joint bleeds and treatment without concurrent bleeds in a HA rat model. Method HA rats were divided into two groups: one group (n...... = 10) receiving three needle induced knee joint bleeds 14 days apart and a control group (n = 9) receiving three sham procedures. Three hours after each injury/sham 50 IU kg−1 rhFVIII was administrated intravenously. Subsequently, both groups continued rhFVIII treatment for another 9 weeks. Binding...

  20. Transforming growth factor-β1 induces expression of human coagulation factor XII via Smad3 and JNK signaling pathways in human lung fibroblasts.

    Science.gov (United States)

    Jablonska, Ewa; Markart, Philipp; Zakrzewicz, Dariusz; Preissner, Klaus T; Wygrecka, Malgorzata

    2010-04-09

    Coagulation factor XII (FXII) is a liver-derived serine protease involved in fibrinolysis, coagulation, and inflammation. The regulation of FXII expression is largely unknown. Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that has been linked to several pathological processes, including tissue fibrosis by modulating procoagulant and fibrinolytic activities. This study investigated whether TGF-beta1 may regulate FXII expression in human lung fibroblasts. Treatment of human lung fibroblasts with TGF-beta1 resulted in a time-dependent increase in FXII production, activation of p44/42, p38, JNK, and Akt, and phosphorylation and translocation into the nucleus of Smad3. However, TGF-beta1-induced FXII expression was repressed only by the JNK inhibitor and JNK and Smad3 antisense oligonucleotides but not by MEK, p38, or phosphoinositide 3-kinase blockers. JNK inhibition had no effect on TGF-beta1-induced Smad3 phosphorylation, association with Smad4, and its translocation into the nucleus but strongly suppressed Smad3-DNA complex formation. FXII promoter analysis revealed that the -299/+1 region was sufficient for TGF-beta1 to induce FXII expression. Sequence analysis of this region detected a potential Smad-binding element at position -272/-269 (SBE-(-272/-269)). Chromatin immunoprecipitation and streptavidin pulldown assays demonstrated TGF-beta1-dependent Smad3 binding to SBE-(-272/-269). Mutation or deletion of SBE-(-272/-269) substantially reduced TGF-beta1-mediated activation of the FXII promoter. Clinical relevance was demonstrated by elevated FXII levels and its co-localization with fibroblasts in the lungs of patients with acute respiratory distress syndrome. Our results show that JNK/Smad3 pathway plays a critical role in TGF-beta1-induced FXII expression in human lung fibroblasts and implicate its possible involvement in pathological conditions characterized by elevated TGF-beta1 levels.

  1. Studies on coagulation, fibrinolysis, kallikrein-kinin and complement activation in systemic and pulmonary circulation during hip arthroplasty with acrylic cement.

    Science.gov (United States)

    Dahl, O E; Molnar, I; Vinje, A; Rø, J S; Kierulf, P; Andersen, A B; Dalaker, K; Prydz, H

    1988-06-15

    This study was designed to evaluate the contribution of the plasma cascade systems to the cardiopulmonary complications, occasionally leading to sudden death during hip arthroplasty using acrylic cement. The intraoperative pattern following uneventful surgery was therefore investigated in 8 patients with osteoarthrosis with frequent sampling from the radial and pulmonary arteries. The following general findings emerged: A gradual consumption of coagulation factors (platelets, fibrinogen, factor VII, antithrombin III), fibrinolytic components (plasminogen, alpha-2-antiplasmin), kallikrein-kinin factors (prekallikrein, kallikrein inhibitor) and complement factors (C3c, C4) was observed. Some intrapulmonary proteolytic inhibition was noticed as evidenced by lower arterial than mixed venous blood levels of alpha-2-antiplasmin and kallikrein inhibitor. Insignificant changes occurred for factor VII-phospholipid complex. A rapid, massive and transient increase in fibrinopeptide A (FPA) values in the radial artery, as opposed to the moderate increase in the pulmonary artery, was found immediately after reaming and broaching of bone. This probably reflected intrapulmonary fibrinogen to fibrin conversion, reaching a maximum 15-20 minutes before the femoral implantation. As estimated from the FPA arterial peak values and the fall in fibrinogen concentrations, approximately 5-10% of the circulating fibrinogen molecules were devoided of FPA during this intraoperative phase. The marked a-v difference in FPA level supports earlier findings of intrapulmonary fibrin formation and deposition. This process, however preceded the critical period of cardiorespiratory collapse (CRC) by at least 15 minutes, and may thus predispose to this complication.

  2. Association of ABO blood groups with von Willebrand factor, factor VIII and ADAMTS-13 in patients with lung cancer.

    Science.gov (United States)

    Liu, Xia; Chen, Xiaogang; Yang, Jiezuan; Guo, Renyong

    2017-09-01

    Coagulative and fibrinolytic disorders appear to be associated with the development of lung cancer. The aim of the present study was to determine plasma levels of von Willebrand factor (VWF) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif 13 (ADAMTS-13), and factor VIII (FVIII) activity, in association with O and non-O blood groups in patients with lung cancer. Plasma levels of VWF and ADAMTS-13, and FVIII activity were measured in 115 patients with lung cancer and 98 healthy subjects. Phenotyping of the ABO blood groups was also performed for the two groups. Significantly increased VWF levels and FVIII activity, as well as significantly decreased ADAMTS-13 levels, were observed in patients with distant metastasis as compared with those without distant metastasis and the healthy controls. Plasma VWF levels and FVIII activity were significantly increased in subjects with non-O type blood compared with those with type O blood in the two groups. However, a significant decrease in ADAMTS-13 levels was observed only in the control group among those with non-O type blood, compared with those with type O blood. The results of the present study indicate that increased VWF and decreased ADAMTS-13 levels facilitate the invasiveness and metastasis of lung cancer. Non-O blood groups constitute a risk factor for increased VWF and FVIII in plasma. Continued monitoring of VWF and ADAMTS-13 levels, and of FVIII activity in patients with lung cancer with distinct blood groups may help to minimize the incidence of thrombotic events and improve assessment of disease progression.

  3. Splenectomy Improves Hemostatic and Liver Functions in Hepatosplenic Schistosomiasis Mansoni.

    Directory of Open Access Journals (Sweden)

    Luiz Arthur Calheiros Leite

    Full Text Available Schistosomiasis mansoni is a chronic liver disease, in which some patients (5-10% progress to the most severe form, hepatosplenic schistosomiasis. This form is associated with portal hypertension and splenomegaly, and often episodes of gastrointestinal bleeding, even with liver function preserved. Splenectomy is a validated procedure to reduce portal hypertension following digestive bleeding. Here, we evaluate beneficial effects of splenectomy on blood coagulation factors and liver function tests in hepatosplenic schistosomiasis mansoni compared to non-operated patients.Forty-five patients who had undergone splenectomy surgery were assessed by laboratory analyses and ultrasound examination and compared to a non-operated group (n = 55. Blood samples were obtained for liver function tests, platelet count and prothrombin time. Coagulation factors (II, VII, VIII, IX and X, protein C and antithrombin IIa, plasminogen activator inhibitor-1 were measured by routine photometric, chromogenic or enzyme-linked immunosorbent assays, while hyperfibrinolysis was defined by plasminogen activator inhibitor-1 levels. Both groups had similar age, gender and pattern of periportal fibrosis. Splenectomized patients showed significant reductions in portal vein diameter, alkaline phosphatase and bilirubin levels compared to non-operated patients, while for coagulation factors there were significant improvement in prothrombin, partial thromboplastin times and higher levels of factor VII, VIII, IX, X, protein C and plasminogen activator inhibitor-1.This study shows that the decrease of flow pressure in portal circulation after splenectomy restores the capacity of hepatocyte synthesis, especially on the factor VII and protein C levels, and these findings suggest that portal hypertension in patients with hepatosplenic schistosomiasis influences liver functioning and the blood coagulation status.

  4. Coagulation profile in patients undergoing video-assisted thoracoscopic lobectomy

    DEFF Research Database (Denmark)

    Christensen, Thomas Decker; Vad, Henrik; Pedersen, Søren

    2017-01-01

    -, and the first two days postoperatively by standard coagulation blood test, thromboelastometry (ROTEM®) and thrombin generation. Results: Patients undergoing potential curative surgery for lung cancer were not hypercoagulable preoperatively. There was no statistically significant difference in the majority......Background: Knowledge about the impact of Low-Molecular-Weight Heparin (LMWH) on the coagulation system in patients undergoing minimal invasive lung cancer surgery is sparse. The aim of this study was to assess the effect of LMWH on the coagulation system in patients undergoing Video......-Assisted Thoracoscopic Surgery (VATS) lobectomy for primary lung cancer. Methods: Sixty-three patients diagnosed with primary lung cancer undergoing VATS lobectomy were randomized to either subcutaneous injection with dalteparin (Fragmin®) 5000 IE once daily or no intervention. Coagulation was assessed pre-, peri...

  5. The effects of ropivacaine hydrochloride on coagulation and fibrinolysis. An assessment using thromboelastography.

    LENUS (Irish Health Repository)

    Porter, J M

    2012-02-03

    Amide local anaesthetics impair coagulation by inhibition of platelet function and enhanced fibrinolysis. The potential therefore exists that the presence of amide local anaesthetics in the epidural space could contribute to the therapeutic failure of an epidural autologous blood patch. Ropivacaine is an aminoamide local anaesthetic increasingly used for epidural analgesia and anaesthesia, particularly in obstetric practice. This study was undertaken to investigate whether concentrations of ropivacaine in blood, which could occur clinically in the epidural space, alter coagulation or fibrinolysis. Thromboelastography was used to assess clotting and fibrinolysis of blood to which ropivacaine had been added. Although modest alterations in maximum amplitude, coagulation time and alpha angle were observed, the effect of ropivacaine on clotting and fibrinolysis was not clinically significant. We conclude that it is unlikely that the presence of ropivacaine in the epidural space would reduce the efficacy of an early or prophylactic epidural blood patch.

  6. Interplay between coagulation and vascular inflammation in sickle cell disease

    Science.gov (United States)

    Sparkenbaugh, Erica; Pawlinski, Rafal

    2013-01-01

    Sickle cell disease is the most common inherited hematologic disorder that leads to the irreversible damage of multiple organs. Although sickling of red blood cells and vaso-occlusion are central to the pathophysiology of sickle cell disease the importance of hemolytic anemia and vasculopathy has been recently recognized. Hypercoagulation state is another prominent feature of sickle cell disease and is mediated by activation of both intrinsic and extrinsic coagulation pathways. Growing evidence demonstrates that coagulation may not only contribute to the thrombotic complications, but also to vascular inflammation associated with this disease. This article summarizes the role of vascular inflammation and coagulation activation, discusses potential mechanisms responsible for activation of coagulation and reviews recent data demonstrating the crosstalk between coagulation and vascular inflammation in sickle cell disease. PMID:23593937

  7. Defibrotide Interferes With Several Steps of the Coagulation-Inflammation Cycle and Exhibits Therapeutic Potential to Treat Severe Malaria

    Czech Academy of Sciences Publication Activity Database

    Francischetti, I.M.B.; Oliveira, C. J.; Ostera, G. R.; Yager, S. B.; Debierre-Grockiego, F.; Carregaro, V.; Jaramillo-Gutierrez, G.; Hume, J. C. C.; Jiang, L.; Moretz, S. E.; Lin, Ch. K.; Ribeiro, J.M.C.; Long, C. A.; Vickers, B. K.; Schwarz, R. T.; Seydel, K. B.; Iacobelli, M.; Ackerman, H. C.; Srinivasan, P.; Gomes, R. B.; Wang, X.; Monteiro, R.Q.; Kotsyfakis, Michalis; Sa-Nunes, A.; Waisberg, M.

    2012-01-01

    Roč. 32, č. 3 (2012), s. 786-798 ISSN 1079-5642 Institutional research plan: CEZ:AV0Z60220518 Keywords : anticoagulants * blood coagulation * endothelium * microcirculation * vascular biology * malaria * defibrotide * inflammation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.338, year: 2012

  8. Selective serotonin reuptake inhibitors and intraoperative blood pressure.

    Science.gov (United States)

    van Haelst, Ingrid M M; van Klei, Wilton A; Doodeman, Hieronymus J; Kalkman, Cor J; Egberts, Toine C G

    2012-02-01

    The influence of selective serotonin reuptake inhibitors (SSRIs) on blood pressure is poorly understood. We hypothesized that if SSRIs have an influence on blood pressure, this might become manifest in changes in intraoperative blood pressure. We aimed to study the association between perioperative use of SSRIs and changes in intraoperative blood pressure by measuring the occurrence of intraoperative hyper- and hypotension. We conducted a retrospective observational follow-up study among patients who underwent elective primary total hip arthroplasty. The index group included users of SSRIs. The reference group included a random sample (ratio 1:3) of nonusers of an antidepressant agent. The outcome was the occurrence of intraoperative hypo- and hypertensive episodes (number, mean and total duration, and area under the curve (AUC)). The outcome was adjusted for confounding factors using regression techniques. The index group included 20 users of an SSRI. The reference group included 60 nonusers. Users of SSRIs showed fewer intraoperative hypotensive episodes, a shorter mean and total duration, and a smaller AUC when compared to the reference group. After adjustment for confounders, SSRI use was associated with a significantly shorter total duration of hypotension: mean difference of -29.4 min (95% confidence interval (CI) -50.4 to -8.3). Two users of an SSRI and two patients in the reference group had a hypertensive episode. Continuation of treatment with SSRIs before surgery was associated with a briefer duration of intraoperative hypotension.

  9. Computational study of some benzamidine-based inhibitors of thrombin-like snake venom proteinases

    Science.gov (United States)

    Henriques, Elsa S.; Nascimento, Marco A. C.; Ramos, Maria João

    Pit viper venoms contain a number of serine proteinases that, despite their observed coagulant thrombin-like action in vitro, exhibit a paradoxical benign defibrinogenating (anticoagulant) action in vivo, with clinical applications in preventing thrombi and improved blood circulation. Considering that several benzamidine-based inhibitors, some highly selective to thrombin, also inhibit the enzymatic activity of such venombins, the modeling of their enzyme-inhibitor interactions could provide valuable information on the topological factors that determine the divergences in activity. The first step, and the object of the present study, was to derive the necessary set of parameters, consistent with the CHARMM force field, and to perform molecular dynamics (MD) simulations on a few selected representatives of the inhibitors in question under physiological conditions. Bonding and van der Waals parameters were derived by analogy to similar ones in the existing force field. Net atomic charges were obtained with a restrained fitting to the molecular electrostatic potential generated at B3LYP/6-31G(d) level. The parameters were refined to reproduce the available experimental geometries and crystal data, and the MD simulations of the free inhibitors in aqueous solution at 298 K provided an insightful description of their available conformational space.

  10. [Role and clinical significance of coagulation and inflammatory factors in moderate and severe ovarian endometriosis].

    Science.gov (United States)

    Lin, Q; Ding, S J; Zhu, T H; Li, T T; Huang, X F; Zhang, X M

    2018-03-25

    Objective: To determine the levels of coagulation and inflammatory factors in women with moderate and severe ovarian endometriosis so as to investigate the possible role of coagulation and inflammatory factors in the pathogenesis, diagnosis and treatment of this disease. Methods: From June 2015 and June 2017, clinical data of 366 patients with pathologically diagnosed moderate and severe ovarian endometriosis (case group) and 244 patients with pathologically diagnosed benign ovarian cysts (control group) in Women's Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The levels of coagulation indicators, inflammatory factors and serum tumor markers were measured. Then, the values of these indicators in diagnosis of endometriosis were analyzed. Results: (1) The levels of plasma prothrombin time (PT) and thrombin time (TT) in patients with ovarian endometriosis [median: 12.8 s (range: 12.4-13.2 s) and 15.5 s (range: 15.1-15.9 s), respectively] were significantly shorter than those with benign ovarian cysts [median: 13.0 s (range: 12.5-13.4 s) and 15.7 s (range: 15.3-16.1 s), respectively; all P endometriosis were significantly higher than those with benign ovarian cysts [median: 2.8 g/L (range: 2.6-3.2 g/L) and 0.6 mg/L (range: 0.4-1.2 mg/L), respectively; P =0.000]. Moreover, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio [PLR; median: 2.3 (range: 1.8-3.1) and 144 (range: 113-179), respectively] in patients with ovarian endometriosis were significantly higher than those with benign ovarian cysts [median: 2.1 (range: 1.6-2.8) and 128 (range: 104-165), respectively; P endometriosis, the levels of PT were significantly shorter in stage Ⅳ endometriosis than that in stage Ⅲ endometriosis ( P endometriosis were significantly higher than those in patients with stage Ⅲ endometriosis ( P endometriosis, and the detection of coagulation and inflammatory factors may be have important clinical significance for the

  11. Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides.

    Science.gov (United States)

    Fonseca, Roberto J C; Oliveira, Stephan-Nicollas M C G; Pomin, Vitor H; Mecawi, André S; Araujo, Iracema G; Mourão, Paulo A S

    2010-05-01

    We report the effects of a chemically oversulfated chondroitin sulfate and a naturally fucosylated chondroitin sulfate on the coagulation system. The former has been recently identified as a contaminant of heparin preparations and the latter has been proposed as an alternative anticoagulant. The mechanism of action of these polymers on coagulation is complex and target different components of the coagulation system. They have serpin-independent anticoagulant activity, which preponderates in plasma. They also have serpin-dependent anticoagulant activity but differ significantly in the target coagulation protease and preferential serpin. Their anticoagulant effects differ even more markedly when tested as inhibitors of coagulation proteases using plasma as a source of serpins. It is possible that the difference is due to the high availability of fucosylated chondroitin sulfate whereas oversulfated chondroitin sulfate has strong unspecific binding to plasma protein and low availability for the binding to serpins. When tested using a venous thrombosis experimental model, oversulfated chondroitin sulfate is less potent as an antithrombotic agent than fucosylated chondroitin sulfate. These highly sulfated chondroitin sulfates activate factor XII in in vitro assays, based on kallikrein release. However, only fucosylated chondroitin sulfate induces hypotension when intravenously injected into rats. In conclusion, the complexity of the regulatory mechanisms involved in the action of highly sulfated polysaccharides in coagulation requires their analysis by a combination of in vitro and in vivo assays. Our results are relevant due to the urgent need for new anticoagulant drugs or alternative sources of heparin.

  12. Influential factors of formation kinetics of flocs produced by water treatment coagulants.

    Science.gov (United States)

    Wu, Chunde; Wang, Lin; Hu, Bing; Ye, Jian

    2013-05-01

    The growth rate and size of floc formation is of great importance in water treatment especially in coagulation process. The floc formation kinetics and the coagulation efficiency of synthetic water were investigated by using an on-line continuous optical photometric dispersion analyze and the analysis of water quality. Experimental conditions such as alum dosage, pH value for coagulation, stirring intensity and initial turbidity were extensively examined. The photometric dispersion analyze results showed that coagulation of kaolin suspensions with two coagulants (alum and polyaluminium chloride) could be taken as a two-phase process: slow and rapid growth periods. Operating conditions with higher coagulant doses, appropriate pH and average shear rate might be particularly advantageous. The rate of overall floc growth was mainly determined by a combination of hydraulic and water quality conditions such as pH and turbidity. The measurement of zeta potential indicates that polyaluminium chloride exhibited higher charge-neutralizing ability than alum and achieved lower turbidities than alum for equivalent Al dosages. Under the same operating conditions, the alum showed a higher grow rate, but with smaller floc size.

  13. Multipurpose HTS Coagulation Analysis: Assay Development and Assessment of Coagulopathic Snake Venoms

    Directory of Open Access Journals (Sweden)

    Kristina B. M. Still

    2017-11-01

    Full Text Available Coagulation assays currently employed are often low throughput, require specialized equipment and/or require large blood/plasma samples. This study describes the development, optimization and early application of a generic low-volume and high-throughput screening (HTS assay for coagulation activity. The assay is a time-course spectrophotometric measurement which kinetically measures the clotting profile of bovine or human plasma incubated with Ca2+ and a test compound. The HTS assay can be a valuable new tool for coagulation diagnostics in hospitals, for research in coagulation disorders, for drug discovery and for venom research. A major effect following envenomation by many venomous snakes is perturbation of blood coagulation caused by haemotoxic compounds present in the venom. These compounds, such as anticoagulants, are potential leads in drug discovery for cardiovascular diseases. The assay was implemented in an integrated analytical approach consisting of reversed-phase liquid chromatography (LC for separation of crude venom components in combination with parallel post-column coagulation screening and mass spectrometry (MS. The approach was applied for the rapid assessment and identification of profiles of haemotoxic compounds in snake venoms. Procoagulant and anticoagulant activities were correlated with accurate masses from the parallel MS measurements, facilitating the detection of peptides showing strong anticoagulant activity.

  14. Associations of activated coagulation factor VII and factor VIIa-antithrombin levels with genome-wide polymorphisms and cardiovascular disease risk.

    Science.gov (United States)

    Olson, N C; Raffield, L M; Lange, L A; Lange, E M; Longstreth, W T; Chauhan, G; Debette, S; Seshadri, S; Reiner, A P; Tracy, R P

    2018-01-01

    Essentials A fraction of coagulation factor VII circulates in blood as an activated protease (FVIIa). We evaluated FVIIa and FVIIa-antithrombin (FVIIa-AT) levels in the Cardiovascular Health Study. Polymorphisms in the F7 and PROCR loci were associated with FVIIa and FVIIa-AT levels. FVIIa may be an ischemic stroke risk factor in older adults and FVIIa-AT may assess mortality risk. Background A fraction of coagulation factor (F) VII circulates as an active protease (FVIIa). FVIIa also circulates as an inactivated complex with antithrombin (FVIIa-AT). Objective Evaluate associations of FVIIa and FVIIa-AT with genome-wide single nucleotide polymorphisms (SNPs) and incident coronary heart disease, ischemic stroke and mortality. Patients/Methods We measured FVIIa and FVIIa-AT in 3486 Cardiovascular Health Study (CHS) participants. We performed a genome-wide association scan for FVIIa and FVIIa-AT in European-Americans (n = 2410) and examined associations of FVII phenotypes with incident cardiovascular disease. Results In European-Americans, the most significant SNP for FVIIa and FVIIa-AT was rs1755685 in the F7 promoter region on chromosome 13 (FVIIa, β = -25.9 mU mL -1 per minor allele; FVIIa-AT, β = -26.6 pm per minor allele). Phenotypes were also associated with rs867186 located in PROCR on chromosome 20 (FVIIa, β = 7.8 mU mL -1 per minor allele; FVIIa-AT, β = 9.9 per minor allele). Adjusted for risk factors, a one standard deviation higher FVIIa was associated with increased risk of ischemic stroke (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.01, 1.23). Higher FVIIa-AT was associated with mortality from all causes (HR, 1.08; 95% CI, 1.03, 1.12). Among European-American CHS participants the rs1755685 minor allele was associated with lower ischemic stroke (HR, 0.69; 95% CI, 0.54, 0.88), but this association was not replicated in a larger multi-cohort analysis. Conclusions The results support the importance of the F7 and PROCR loci in

  15. Model of a ternary complex between activated factor VII, tissue factor and factor IX.

    Science.gov (United States)

    Chen, Shu-wen W; Pellequer, Jean-Luc; Schved, Jean-François; Giansily-Blaizot, Muriel

    2002-07-01

    Upon binding to tissue factor, FVIIa triggers coagulation by activating vitamin K-dependent zymogens, factor IX (FIX) and factor X (FX). To understand recognition mechanisms in the initiation step of the coagulation cascade, we present a three-dimensional model of the ternary complex between FVIIa:TF:FIX. This model was built using a full-space search algorithm in combination with computational graphics. With the known crystallographic complex FVIIa:TF kept fixed, the FIX docking was performed first with FIX Gla-EGF1 domains, followed by the FIX protease/EGF2 domains. Because the FIXa crystal structure lacks electron density for the Gla domain, we constructed a chimeric FIX molecule that contains the Gla-EGF1 domains of FVIIa and the EGF2-protease domains of FIXa. The FVIIa:TF:FIX complex has been extensively challenged against experimental data including site-directed mutagenesis, inhibitory peptide data, haemophilia B database mutations, inhibitor antibodies and a novel exosite binding inhibitor peptide. This FVIIa:TF:FIX complex provides a powerful tool to study the regulation of FVIIa production and presents new avenues for developing therapeutic inhibitory compounds of FVIIa:TF:substrate complex.

  16. Risk Factors for Inhibitor Formation in Hemophilia: A Prevalent Case-Control Study

    Science.gov (United States)

    Ragni, Margaret V.; Ojeifo, Oluseyi; Feng, Jinong; Yan, Jin; Hill, Kathleen A.; Sommer, Steve S.; Trucco, Massimo N.; Brambilla, Donald J.

    2009-01-01

    Background Inhibitor formation is a major complication of hemophilia treatment. Aim In a prevalent case-control study, we evaluated blood product exposure, genotype, and HLA type on hemophilia A inhibitor formation. Methods Product exposure was extracted from medical records. Genotype was determined on stored DNA samples by detection of virtually all mutations-SSCP (DOVAM-S) and subcycling PCR. HLA typing was performed by PCR amplification and exonuclease-released fluorescence. Results Cases experienced higher intensity factor, 455 vs. 200 U per exposure, p0.100. Genotype was not associated with race. Time to immune tolerance was shorter for titers 0.50. Conclusions Inhibitor formation is associated with high intensity product exposure, CNS bleeding, African-American race, and low frequency of missense mutations. The ideal time to initiate prophylaxis to reduce CNS bleeding and inhibitor formation will require prospective studies. PMID:19563499

  17. Association of air pollution sources and aldehydes with biomarkers of blood coagulation, pulmonary inflammation, and systemic oxidative stress.

    Science.gov (United States)

    Altemose, Brent; Robson, Mark G; Kipen, Howard M; Ohman Strickland, Pamela; Meng, Qingyu; Gong, Jicheng; Huang, Wei; Wang, Guangfa; Rich, David Q; Zhu, Tong; Zhang, Junfeng

    2017-05-01

    Using data collected before, during, and after the 2008 Summer Olympic Games in Beijing, this study examines associations between biomarkers of blood coagulation (vWF, sCD62P and sCD40L), pulmonary inflammation (EBC pH, EBC nitrite, and eNO), and systemic oxidative stress (urinary 8-OHdG) with sources of air pollution identified utilizing principal component analysis and with concentrations of three aldehydes of health concern. Associations between the biomarkers and the air pollution source types and aldehydes were examined using a linear mixed effects model, regressing through seven lag days and controlling for ambient temperature, relative humidity, gender, and day of week for the biomarker measurements. The biomarkers for pulmonary inflammation, particularly EBC pH and eNO, were most consistently associated with vehicle and industrial combustion, oil combustion, and vegetative burning. The biomarkers for blood coagulation, particularly vWF and sCD62p, were most consistently associated with oil combustion. Systemic oxidative stress biomarker (8-OHdG) was most consistently associated with vehicle and industrial combustion. The associations of the biomarkers were generally not significant or consistent with secondary formation of pollutants and with the aldehydes. The findings support policies to control anthropogenic pollution sources rather than natural soil or road dust from a cardio-respiratory health standpoint.

  18. Preliminary study of haemostasis in irradiated-enterectomised dog. Primary haemostasis, coagulation, plasma factors exploration

    International Nuclear Information System (INIS)

    Dubos, M.; Niaussat, P.M.; Neveux, Y.; Nguyen, T.L.; Drouet, J.; Bac, P.

    Some hematological changes due to the combined effects of ionizing radiations and surgery were studied in dogs irradiated at 250, 300 and 350R. A constant hemorrhagic syndrome was observed with an impairment of the platelets functions and a depletion of several coagulation factors [fr

  19. Blocking of platelets or intrinsic coagulation pathway-driven thrombosis does not prevent cerebral infarctions induced by photothrombosis.

    Science.gov (United States)

    Kleinschnitz, Christoph; Braeuninger, Stefan; Pham, Mirko; Austinat, Madeleine; Nölte, Ingo; Renné, Thomas; Nieswandt, Bernhard; Bendszus, Martin; Stoll, Guido

    2008-04-01

    Models of photochemically-induced thrombosis are widely used in cerebrovascular research. Photothrombotic brain infarctions can be induced by systemic application of photosensitizing dyes followed by focal illumination of the cerebral cortex. Although the ensuing activation of platelets is well established, their contribution for thrombosis and tissue damage has not formally been proved. Infarction to the cerebral cortex was induced in mice by Rose Bengal and a cold light source. To assess the functional role of platelets, animals were platelet-depleted by anti-GPIbalpha antibodies or treated with GPIIb/IIIa-blocking F(ab)(2) fragments. The significance of the plasmatic coagulation cascade was determined by using blood coagulation factor XII (FXII)-deficient mice or heparin. Infarct development and infarct volumes were determined by serial MRI and conventional and electron microscopy. There was no difference in development and final size of photothrombotic infarctions in mice with impaired platelet function. Moreover, deficiency of FXII, which initiates the intrinsic pathway of coagulation and is essential for thrombus formation, or blockade of FXa, the key protease during the waterfall cascade of plasmatic coagulation, by heparin likewise did not affect lesion development. Our data demonstrate that platelet activation, factor XII-driven thrombus formation, and plasmatic coagulation pathways downstream of FX are not a prerequisite for ensuing tissue damage in models of photothrombotic vessel injury indicating that other pathomechanisms are involved. We suggest that this widely used model does not depend on platelet- or plasmatic coagulation-derived thrombosis.

  20. Coagulation activity in liver disease | Reza | Internet Journal of ...

    African Journals Online (AJOL)

    Patients with advanced hepatic failure may present with the entire spectrum of coagulation factor deficiencies. This study was designed to determine laboratory abnormalities in coagulation in chronic liver disease and the association of these abnormalities with the extent of chronic hepatitis and cirrhosis. Coagulation ...

  1. Coagulation factor VII, serum-triglycerides and the R/Q353 polymorphism: differences between older men and women

    NARCIS (Netherlands)

    Mennen, L. I.; de Maat, M. P.; Schouten, E. G.; Kluft, C.; de Jong, P. T.; Hofman, A.; Grobbee, D. E.

    1997-01-01

    Coagulation factor VII activity (FVII:C) is a risk indicator for cardiovascular disease. It is related to serum-triglycerides and the R/Q353 polymorphism (alleles R and Q) in the gene coding for factor VII is strongly associated with factor VII. The association of serum-triglycerides with factor VII

  2. Coagulation factor VII, serum-triglycerides and the R/Q353 polymorphism: Differences between older men and women

    NARCIS (Netherlands)

    Mennen, L.I.; Maat, M.P.M. de; Schouten, E.G.; Kluft, C.; Jong, P.T.V.M. de; Hofman, A.; Grobbee, D.E.

    1997-01-01

    Coagulation factor VII activity (FVII:C) is a risk indicator for cardiovascular disease. It is related to serum-triglycerides and the R/Q353 polymorphism (alleles R and Q) in the gene coding for factor VII is strongly associated with factor VU[. The association of serum-triglycerides with factor VII

  3. [Molecular genetic analysis for a pedigree with severe hereditary coagulation factor VII deficiency].

    Science.gov (United States)

    Ding, Qiu-lan; Wang, Hong-li; Wang, Xue-feng; Wang, Ming-shan; Fu, Qi-hua; Wu, Wen-man; Hu, Yi-qun; Wang, Zhen-yi

    2003-10-01

    To identify the genetic mutations of a severe inherited coagulation factor VII (FVII) deficiency pedigree. The diagnosis was validated by coagulant and haemostatic parameters. FVII gene mutations were screened in the propositus and his family members by DNA direct sequencing and confirmed by digestions of the restriction enzymes of the PCR production. Two heterozygous missense mutations were found in the propositus of the pedigree: a G to T transversion at position 9482 in exon 6 and a C to T mutation at position 11348 in exon 8 resulting in the amino acid substitution of Arg152 with Leu and Arg304 with Trp, respectively. A heterozygous single nucleotide deletion (C) at position 11487-11489(CCC) within exon 8 was identified, which predicted the frameshift mutation at position His351 followed by the changes of six corresponding amino acids and appearance of a premature protein caused by stop codon. The heterozygous mutations identified in the proband were derived from his father (Arg152 to Leu) and his mother (Arg304 to Trp mutation) and a heterozygous deletion (C) at position 11487-9(CCC). By tracing the other pedigree members, it was found that his grandmother had a heterozygous mutation of Arg304Trp and a heterozygous polymorphism of Arg353Gln and his grandfather had a heterozygous Arg152Leu mutation. Three heterozygous mutations were found in a pedigree with hereditary coagulation factor VII deficiency. Arg152Leu and deletion C at position 11487-9(CCC) were novel mutations.

  4. Sodium-glucose co-transporter type 2 inhibitors reduce evening home blood pressure in type 2 diabetes with nephropathy.

    Science.gov (United States)

    Takenaka, Tsuneo; Kishimoto, Miyako; Ohta, Mari; Tomonaga, Osamu; Suzuki, Hiromichi

    2017-05-01

    The effects of sodium-glucose co-transporter type 2 inhibitors on home blood pressure were examined in type 2 diabetes with nephropathy. The patients with diabetic nephropathy were screened from medical records in our hospitals. Among them, 52 patients who measured home blood pressure and started to take sodium-glucose co-transporter type 2 inhibitors were selected. Clinical parameters including estimated glomerular filtration rate, albuminuria and home blood pressure for 6 months were analysed. Sodium-glucose co-transporter type 2 inhibitors (luseogliflozin 5 mg/day or canagliflozin 100 mg/day) reduced body weight, HbA1c, albuminuria, estimated glomerular filtration rate and office blood pressure. Although sodium-glucose co-transporter type 2 inhibitors did not alter morning blood pressure, it reduced evening systolic blood pressure. Regression analyses revealed that decreases in evening blood pressure predicted decrements in albuminuria. The present data suggest that sodium-glucose co-transporter type 2 inhibitors suppress sodium overload during daytime to reduce evening blood pressure and albuminuria.

  5. Role of altered coagulation-fibrinolytic system in the pathophysiology of diabetic retinopathy.

    Science.gov (United States)

    Behl, Tapan; Velpandian, Thirumurthy; Kotwani, Anita

    2017-05-01

    The implications of altered coagulation-fibrinolytic system in the pathophysiology of several vascular disorders, such as stroke and myocardial infarction, have been well researched upon and established. However, its role in the progression of diabetic retinopathy has not been explored much. Since a decade, it is known that hyperglycemia is associated with a hypercoagulated state and the various impairments it causes are well acknowledged as independent risk factors for the development of cardiovascular diseases. But recent studies suggest that the hypercoagulative state and diminished fibrinolytic responses might also alter retinal homeostasis and induce several deleterious molecular changes in retinal cells which aggravate the already existing hyperglycemia-induced pathological conditions and thereby lead to the progression of diabetic retinopathy. The major mediators of coagulation-fibrinolytic system whose concentration or activity get altered during hyperglycemia include fibrinogen, antithrombin-III (AT-III), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF). Inhibiting the pathways by which these altered mediators get involved in the pathophysiology of diabetic retinopathy can serve as potential targets for the development of an adjuvant novel alternative therapy for diabetic retinopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Tissue factor-expressing tumor cells can bind to immobilized recombinant tissue factor pathway inhibitor under static and shear conditions in vitro.

    Directory of Open Access Journals (Sweden)

    Sara P Y Che

    Full Text Available Mammary tumors and malignant breast cancer cell lines over-express the coagulation factor, tissue factor (TF. High expression of TF is associated with a poor prognosis in breast cancer. Tissue factor pathway inhibitor (TFPI, the endogenous inhibitor of TF, is constitutively expressed on the endothelium. We hypothesized that TF-expressing tumor cells can bind to immobilized recombinant TFPI, leading to arrest of the tumor cells under shear in vitro. We evaluated the adhesion of breast cancer cells to immobilized TFPI under static and shear conditions (0.35 - 1.3 dyn/cm2. We found that high-TF-expressing breast cancer cells, MDA-MB-231 (with a TF density of 460,000/cell, but not low TF-expressing MCF-7 (with a TF density of 1,400/cell, adhered to recombinant TFPI, under static and shear conditions. Adhesion of MDA-MB-231 cells to TFPI required activated factor VII (FVIIa, but not FX, and was inhibited by a factor VIIa-blocking anti-TF antibody. Under shear, adhesion to TFPI was dependent on the TFPI-coating concentration, FVIIa concentration and shear stress, with no observed adhesion at shear stresses greater than 1.0 dyn/cm2. This is the first study showing that TF-expressing tumor cells can be captured by immobilized TFPI, a ligand constitutively expressed on the endothelium, under low shear in vitro. Based on our results, we hypothesize that TFPI could be a novel ligand mediating the arrest of TF-expressing tumor cells in high TFPI-expressing vessels under conditions of low shear during metastasis.

  7. Analysis of the complex formation of heparin with protamine by light scattering and analytical ultracentrifugation: implications for blood coagulation management.

    Science.gov (United States)

    Maurer, Jürgen; Haselbach, Stephanie; Klein, Oliver; Baykut, Doan; Vogel, Vitali; Mäntele, Werner

    2011-02-02

    Heparin, a linear glycosaminoglycan, is used in different forms in anticoagulation treatment. Protamine, a highly positive charged peptide containing about 32 amino acids, acts as an antagonist for heparin to restore normal blood coagulation. The complex formation of protamine with heparin was analyzed by a combination of analytical ultracentrifugation and light scattering. Titration of heparin with protamine in blood plasma preparations results in a drastic increase of turbidity, indicating the formation of nanoscale particles. A similar increase of turbidity was observed in physiological saline solution with or without human serum albumin (HSA). Particle size analysis by analytical ultracentrifugation revealed a particle radius of approximately 30 nm for unfractionated heparin and of approximately 60 nm for low molecular weight heparin upon complexation with excess protamine, in agreement with atomic force microscopy data. In the absence of HSA, larger and more heterogeneous particles were observed. The particles obtained were found to be stable for hours. The particle formation kinetics was analyzed by light scattering at different scattering angles and was found to be complete within several minutes. The time course of particle formation suggests a condensation reaction, with sigmoidal traces for low heparin concentrations and quasi-first-order reaction for high heparin concentrations. Under all conditions, the final scattering intensity reached after several minutes was found to be proportional to the amount of heparin in the blood plasma or buffer solution, provided that excess protamine was available and no multiple scattering occurred. On the basis of a direct relation between particle concentration and the heparin concentration present before protaminization, a light scattering assay was developed which permits the quantitative analysis of the heparin concentration in blood plasma and which could complement or even replace the activated clotting time test

  8. [Ratio of erythrocyte and plasma in massive blood transfusion].

    Science.gov (United States)

    Wen, Xian-Hui; Liu, Feng-Xia; Zhang, Jun-Hua; Gui, Rong

    2014-06-01

    This study was purposed to explore the suitable ratio between fresh frozen plasma and erythrocyte by retrospective analysis of coagulation in patients with massive blood transfusion. The clinical data of 151 cases with massive blood transfusion from January 2011 to January 2013 were analyzed retrospectively. According to coagulation, patients were divided into coagulation normal group (138 cases) and coagulation dysfunction group (13 cases). Based on the ratio of 1:1 of fresh frozen plasma and erythrocyte, the patients were divided into high plasma group(2:1), medium plasma group (1:1) and low plasma (blood transfusion. The results showed that prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) were prolonged, fibrinogen (FIB) level decreased significantly (all P blood transfusion 24 h; the high plasma and the medium plasma group of coagulation normal group had no significant changes in coagulation (P > 0.05); prothrombin time, activated partial thromboplastin time, thrombin time and fibrinogen level in the medium plasma and low plasma subgroup of coagulation dysfunction group after massive transfusion was still in abnormal levels (P > 0.05), coagulation function in high plasma subgroup was improved significantly (P blood transfusion, the ratio between fresh frozen plasma and erythrocyte is recommended to be 2:1 in patients of coagulation dysfunction in order to improve the patient's coagulation function and to reduce the incidence of adverse event, the ratio of fresh frozen plasma to erythrocyte is recommended to be 1:1 in patients with normal coagulation so as to reduce the dilutional coagulopathy and hypervolemia of blood.

  9. Large enhancement of functional activity of active site-inhibited factor VIIa due to protein dimerization: insights into mechanism of assembly/disassembly from tissue factor.

    Science.gov (United States)

    Stone, Matthew D; Harvey, Stephen B; Martinez, Michael B; Bach, Ronald R; Nelsestuen, Gary L

    2005-04-26

    Active site-inhibited blood clotting factor VIIa (fVIIai) binds to tissue factor (TF), a cell surface receptor that is exposed upon injury and initiates the blood clotting cascade. FVIIai blocks binding of the corresponding enzyme (fVIIa) or zymogen (fVII) forms of factor VII and inhibits coagulation. Although several studies have suggested that fVIIai may have superior anticoagulation effects in vivo, a challenge for use of fVIIai is cost of production. This study reports the properties of dimeric forms of fVIIai that are cross-linked through their active sites. Dimeric wild-type fVIIai was at least 75-fold more effective than monomeric fVIIai in blocking fVIIa association with TF. The dimer of a mutant fVIIai with higher membrane affinity was 1600-fold more effective. Anticoagulation by any form of fVIIai differed substantially from agents such as heparin and showed a delayed mode of action. Coagulation proceeded normally for the first minutes, and inhibition increased as equilibrium binding was established. It is suggested that association of fVIIa(i) with TF in a collision-dependent reaction gives equal access of inhibitor and enzyme to TF. Assembly was not influenced by the higher affinity and slower dissociation of the dimer. As a result, anticoagulation was delayed until the reaction reached equilibrium. Properties of different dissociation experiments suggested that dissociation of fVIIai from TF occurred by a two-step mechanism. The first step was separation of TF-fVIIa(i) while both proteins remained bound to the membrane, and the second step was dissociation of the fVIIa(i) from the membrane. These results suggest novel actions of fVIIai that distinguish it from most of the anticoagulants that block later steps of the coagulation cascade.

  10. THROMBOPHILIA IN PREGNANCY – CURRENT ISSUE OF MODERN PERINATOLOGY

    Directory of Open Access Journals (Sweden)

    Dragana Radović-Janošević

    2015-09-01

    Full Text Available Pregnancy is a condition of increased affinity to blood clotting. The most important changes of coagulation system in pregnancy involve the increase of the following coagulation factors: fibrinogen production, level of numerous blood coagulation factors- FII, FVII, FVIII, FX, FXII, acquired activated protein C resistance, and the decrease of: fibrinolysis due to the increase of a large number of fibrinolytic activator inhibitors PAI-1 and PAI-2, thrombin activatable fibrinolysis inhibitor TAFI, and levels of proteins S and C. This disease is not a disease on its own, but a group of inherited and acquired coagulation disorders that increase the predisposition to thrombosis. The treatment of choice in pregnancy are low-molecular-weight heparins (LMWHs which are derived from standard heparin by controlled hydrolysis, thus obtaining heparins of a lower molecular mass. The most commonly used LMWHs are: dalteparin sodium, enoxaparin, nadroparin-calcium, reviparin. LMWH is given in prophylactic doses – low and medium doses in therapeutic doses. Thromboprophylaxis in pregnancy is implemented as: intrapartal, intra- and postpartum according to the official recommendations of the American Association of Obstetricians and Gynecologists (ACOG. Specific recommendations of ACOG refer to the treatment of hereditary thrombophilia in pregnancy.

  11. Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation: PROTON-trial

    NARCIS (Netherlands)

    F. Arshad (Freeha); B. Ickx (Brigitte); R.T. van Beem (Rachel); W.G. Polak (Wojciech); F. Grüne (Frank); F. Nevens (Frederik); M. Ilmakunnas (Minna); A.M. Koivusalo (Anna-Maria); H. Isoniemi (Helena); P.F.W. Strengers; H.J.M. Groen (Henk); H.G.D. Hendriks (Herman); T. Lisman (Ton); J. Pirenne (Jacques); R.J. Porte (Robert)

    2013-01-01

    textabstractBackground: In patients with cirrhosis, the synthesis of coagulation factors can fall short, reflected by a prolonged prothrombin time. Although anticoagulants factors are decreased as well, blood loss during orthotopic liver transplantation can still be excessive. Blood loss during

  12. Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation : PROTON-trial

    NARCIS (Netherlands)

    Arshad, Freeha; Ickx, Brigitte; van Beem, Rachel T.; Polak, Wojciech; Grune, Frank; Nevens, Frederik; Ilmakunnas, Minna; Koivusalo, Anna-Maria; Isoniemi, Helena; Strengers, Paul F. W.; Groen, Henk; Hendriks, Herman G. D.; Lisman, Ton; Pirenne, Jacques; Porte, Robert J.

    2013-01-01

    Background: In patients with cirrhosis, the synthesis of coagulation factors can fall short, reflected by a prolonged prothrombin time. Although anticoagulants factors are decreased as well, blood loss during orthotopic liver transplantation can still be excessive. Blood loss during orthotopic liver

  13. Hemostasis in Overt and Subclinical Hyperthyroidism

    Science.gov (United States)

    Ordookhani, Arash; Burman, Kenneth D.

    2017-01-01

    Context There are contradictory results on the effect of hyperthyroidism on hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). The present review focuses on hemostatic changes in overt and subclinical hyperthyroidism. Methods A systematic literature search was conducted employing MEDLINE database. The following words were used for the search: Hyperthyroidism; thyrotoxicosis; Graves disease; goiter, nodular; hemostasis; blood coagulation factors; blood coagulation disorders; venous thromboembolism; bleeding; fibrinolysis. The articles that were related to hyperthyroidism and hemostasis are used in this manuscript. Results Hyperthyroidism, either overt or subclinical, renders a hypercoagulable state, although there are several studies with contradictory findings in the literature. Hypercoagulability may be caused by an increase in the level of various coagulation factors such as factor (F) VIII, FX, FIX, von Willebrand F (vWF), and fibrinogen, while hypofibrinolysis by changes in coagulation parameters such as a decrease in plasmin and plasmin activator or an increase in α2-antiplasmin, plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor Conclusions Although many reports are in favor of a hypercoagulable state in overt hyperthyroidism but this finding at the biochemical level and its clinical implication, on the occurrence of VTE, has yet to be confirmed. PMID:29201071

  14. Coagulation Factors Test

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  15. Effect of individual dietary fatty acids on postprandial activation of blood coagulation factor VII and fibrinolysis in healthy young men

    DEFF Research Database (Denmark)

    Tholstrup, T.; Miller, G.J.; Bysted, Anette

    2003-01-01

    Background: Hypertriglyceridemia may represent a procoagulant state involving disturbances to the hemostatic system. Plasminogen activator inhibitor type 1 (PAI-1) is increased in the presence of hypertriglyceridemia. Free fatty acids (FFAs) in plasma may promote factor VII (FVII) activation...

  16. Plasma Tissue Factor Pathway Inhibitor Levels in Angiographically Defined Coronary Artery Disease Among Saudis

    Directory of Open Access Journals (Sweden)

    Syed Shahid Habib

    2013-05-01

    Full Text Available Objectives: This study was aimed to determine plasma levels of total (TFPI-T and free (TFPI-F tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1, and tissue plasminogen activator (t-PA in a cohort of Saudi patients with chronic stable angiographically defined coronary artery disease (CAD and to determine its correlation with its severity.Methods: This cross sectional study was conducted in the department of physiology and department of cardiology, College of Medicine, and King Khalid University Hospital and King Saud University, Riyadh. Sixty known cases of CAD who had undergone angiography (35 males and 25 females were selected. A control group included 39 (20 males and 19 females healthy subjects. Fasting venous blood samples were analyzed for total (TFPI-T and free (TFPI-F tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1, and tissue plasminogen activator (t-PA. Gensini scores and vessel scores were determined for assessing CAD severity.Results: There were non-significant differences between age, body mass index (BMI and Blood pressure between the controls and CAD subjects. A comparison of hemostatic markers between control and CAD patients showed significantly higher levels of Fibrinogen, PAI-1, TFPI-T and TFPI-F in CAD patients compared to control subjects. But there was no difference in plasma t-PA levels. TFPI-T had a significant positive correlation with severity of disease determined by Gensini Scores (r=0.344; p=0.006 and vessel scores (r=0.338; p=0.015.Conclusion: Plasma levels of total tissue factor pathway inhibitor are significantly related with the presence and severity of CAD. Elevated levels of TFPI-T may be considered as useful diagnostic and prognostic markers in patients with CAD.

  17. Intraventricular hemorrhage in preterm infants: coagulation perspectives.

    Science.gov (United States)

    Kuperman, Amir A; Kenet, Gili; Papadakis, Emmanuel; Brenner, Benjamin

    2011-10-01

    It has long been considered that a severe coagulation deficiency in premature newborns could be a major contributing factor in the occurrence of intraventricular hemorrhage (IVH). High-grade IVH has also been shown to coincide with severe derangement of coagulation in extremely low birth weight infants. This review focuses on the relevance of the physiologically developing immature hemostatic system to IVH, and the potential benefit of agents affecting hemostasis for IVH therapy or prevention in preterm infants. The findings of small, open-label interventional studies on the effect of ethamsylate, vitamin K, fresh frozen plasma, recombinant activated factor VII, and prothrombin complex concentrate on the premature coagulation system will be reviewed. © Thieme Medical Publishers.

  18. Activity of recombinant factor VIIa under different conditions in vitro

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, Jørgen

    2008-01-01

    Recombinant activated factor VII (NovoSeven; Novo Nordisk A/S, Måløv, Denmark) is an effective drug for treatment of bleeding in patients with haemophilia A or B and inhibitors. Little is known about physiological conditions influencing the efficacy of recombinant activated factor VII. We...... investigated the in-vitro effects of pH, temperature, and haemodilution on the activity of recombinant activated factor VII. Samples from eight healthy volunteers were spiked with recombinant activated factor VII (final concentration 1.7 microg/ml) and adjusted to pH 6.0, 6.5, 7.0, and 7.4 or analysed at 30......, 33, 37, and 40 degrees C, or diluted 0, 10, 20, 40, and 60% with dextran before analysis. Samples were analysed as rotational thromboelastometry in whole blood (clotting time, clot formation time, and maximum clot firmness) with and without Innovin (tissue factor), and as factor VII coagulant...

  19. Two-incision laparoscopic appendectomy for a severe hemophilia A child patient with coagulation factor VII deficiency: Case report and review of literature.

    Science.gov (United States)

    He, Jin Peng; Feng, Jie Xiong

    2017-10-01

    The main complication of patients with severe hemophilia is recurrent bleeding events that usually affected musculoskeletal contractures. And replacement therapy methods were continuously improved to minimize adverse impacts brought by those complications. However, only several cases reported about the appendectomy for hemophilia A. We report a case of acute appendicitis treated by two-incision laparoscopy in a boy with hemophilia A and coagulation factor VII deficiency for the first time. An 8y7m-old Chinese boy presented with half a day of right sided abdominal pain, fever, nausea, and vomiting. He received a computed tomography (CT) scan which revealed an enlarged appendix, thickened wall and appendiceal fecalith, and had received a conservative anti-bacterial treatment for his acute appendicitis but failed. He was diagnosed with hemophilia A and coagulation factor VII deficiency. Two-incision laparoscopic appendectomy was made in success with a careful management of perioperative period. We monitored the clotting factor FVIII level and gave him a replacement therapy. The patient had an uneventful recovery. It is important to exclude intraabdominal or retroperitoneal hemorrhage in patients suffering from hemophilia and acute abdominal pain. Pre-operative evaluation of validity of the FVIII replacement therapy is another effective strategy to assess the safety and feasibility of applying an operation procedure. The two-incision laparoscopic appendectomy is an effective treatment for this kind of patients for its minimal trauma and fast recovery characteristics. Our report shows that laparoscopic appendectomy is feasible in a child suffering from hemophilia after adequate blood clotting factor replacement treatment.

  20. Coagulation Profile in Patients with Different Etiologies for Cushing Syndrome: A Prospective Observational Study.

    Science.gov (United States)

    Tirosh, Amit; Lodish, Maya; Lyssikatos, Charalampos; Belyavskaya, Elena; Feelders, Richard A; Stratakis, Constantine A

    2017-05-01

    Previous studies reported a higher prevalence of venous-thromboembolic events among patients with Cushing disease (CD) compared to those with ACTH-independent Cushing syndrome (CS) from adrenal sources. The objective of the current study was to evaluate the coagulation profile of patients with CS from different etiologies. A prospective observational study was conducted at a clinical research center. The study included adult patients admitted for evaluation of suspected CS (n=85), that were divided into 3 groups: CD (n=22), ACTH-independent CS from an adrenal tumor/hyperplasia (adrenal CS, n=21), and a control group consisting of subjects with negative screening for CS (rule-out CS, n=42). Coagulation profiles were drawn before and 8.5±4.3 months after surgery (trans-sphenoidal or adrenalectomy, n=18), and included fibrinogen, Factor VIII (FVIII), von Willebrand factor antigen (vWF:Ag), plasminogen activator inhibitor-1 (PAI-1), antithrombin III (ATIII), Protein C (PC), Protein S (PS), α2-antiplasmin (α2AP), and aPTT measurements. Patients with CD had higher baseline mean cortisol levels, ATIII activity and vWF:Ag levels compared with adrenal CS. Differences in ATIII activity and vWF:Ag levels remained even after controlling for BMI, and ATIII after also controlling for 24-h urinary free cortisol collections. Our study showed for the first time the differences in coagulation profiles between various etiologies of CS. We assume that the higher cortisol burden among CD patients may explain the differences found in the coagulation profile as well as the higher risk for VTE compared with primary adrenal CS patients. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Quality standards for sample collection in coagulation testing.

    Science.gov (United States)

    Lippi, Giuseppe; Salvagno, Gian Luca; Montagnana, Martina; Lima-Oliveira, Gabriel; Guidi, Gian Cesare; Favaloro, Emmanuel J

    2012-09-01

    Preanalytical activities, especially those directly connected with blood sample collection and handling, are the most vulnerable steps throughout the testing process. The receipt of unsuitable samples is commonplace in laboratory practice and represents a serious problem, given the reliability of test results can be adversely compromised following analysis of these specimens. The basic criteria for an appropriate and safe venipuncture are nearly identical to those used for collecting blood for clinical chemistry and immunochemistry testing, and entail proper patient identification, use of the correct technique, as well as appropriate devices and needles. There are, however, some peculiar aspects, which are deemed to be particularly critical when collecting quality specimens for clot-based tests, and these require clearer recognition. These include prevention of prolonged venous stasis, collection of nonhemolyzed specimens, order of draw, and appropriate filling and mixing of the primary collection tubes. All of these important preanalytical issues are discussed in this article, and evidence-based suggestions as well as recommendations on how to obtain a high-quality sample for coagulation testing are also illustrated. We have also performed an investigation aimed to identify variation of test results due to underfilling of primary blood tubes, and have identified a clinically significant bias in test results when tubes are drawn at less than 89% of total fill for activated partial thromboplastin time, less than 78% for fibrinogen, and less than 67% for coagulation factor VIII, whereas prothrombin time and activated protein C resistance remain relatively reliable even in tubes drawn at 67% of the nominal volume. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Effect of elevated levels of coagulation factors on the risk of venous thrombosis in long-distance travelers

    NARCIS (Netherlands)

    Kuipers, Saskia; Cannegieter, Suzanne C.; Doggen, Catharina Jacoba Maria; Rosendaal, Frits R.

    2009-01-01

    Risk of venous thrombosis is increased after long-distance travel. Identifying high-risk groups may provide a basis for targeted prevention. We assessed the effect of increased levels of coagulation factors and combinations of risk factors in travelers in a large case-control study. We calculated

  3. Ambient hemolysis and activation of coagulation is different between HeartMate II and HeartWare left ventricular assist devices.

    Science.gov (United States)

    Birschmann, Ingvild; Dittrich, Marcus; Eller, Thomas; Wiegmann, Bettina; Reininger, Armin J; Budde, Ulrich; Strüber, Martin

    2014-01-01

    Thromboembolic and bleeding events in patients with a left ventricular assist device (LVAD) are still a major cause of complications. Therefore, the balance between anti-coagulant and pro-coagulant factors needs to be tightly controlled. The principle hypothesis of this study is that different pump designs may have an effect on hemolysis and activation of the coagulation system. Referring to this, the HeartMate II (HMII; Thoratec Corp, Pleasanton, CA) and the HeartWare HVAD (HeartWare International Inc, Framingham, MA) were investigated. For 20 patients with LVAD support (n = 10 each), plasma coagulation, full blood count, and clinical chemistry parameters were measured. Platelet function was monitored using platelet aggregometry, platelet function analyzer-100 system ( Siemens, Marburg, Germany), vasodilator-stimulated phosphoprotein phosphorylation assay, immature platelet fraction, platelet-derived microparticles, and von Willebrand diagnostic. Acquired von Willebrand syndrome could be detected in all patients. Signs of hemolysis, as measured by lactate dehydrogenase levels (mean, 470 U/liter HMII, 250 U/liter HVAD; p < 0.001), were more pronounced in the HMII patients. In contrast, D-dimer analysis indicated a significantly higher activation of the coagulation system in HVAD patients (mean, 0.94 mg/liter HMII, 2.01 mg/liter HVAD; p < 0.01). The efficacy of anti-platelet therapy using clopidogrel was not sufficient in more than 50% of the patients. Our results support the finding that all patients with rotary blood pumps suffered from von Willebrand syndrome. In addition, a distinct footprint of effects on hemolysis and the coagulation system can be attributed to different devices. As a consequence, the individual status of the coagulation system needs to be controlled in long-term patients. © 2013 Published by International Society for the Heart and Lung Transplantation on behalf of International Society for Heart and Lung Transplantation.

  4. Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population.

    Science.gov (United States)

    Barillari, Giovanni; Fabbro, Elisabetta; Pasca, Samantha; Bigotto, Enrico

    2009-06-01

    Type 2 diabetes mellitus (DM2) is a metabolic disorder characterized by relative insulin deficiency, insulin resistance and hyperglycemia. DM2 improperly managed can cause severe complications such as renal failure, blindness or arterial disease. In addition to serious complications due to DM2, in the past 20 years, several studies have demonstrated the association between DM2, insulin resistance and prothrombotic risk. In our study, we wanted to evaluate the correlation between coagulation factor levels, oxidative plasmatic levels and DM2. We considered 20 DM2 patients (65% women and 35% men), 40-65 years of age, who had a BMI between 25 and 40 kg/m2 and followed a diet with or without oral antidiabetic treatment and 20 controls, blood donors, 15 men (75%) and five women (25%), who had a BMI between 25 and 40 kg/m2 and their age was between 40 and 65 years. Plasmatic levels of oxidative stress markers (tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein) and coagulation markers (factors VII, VIII, IX, XI, XII, antithrombin III and fibrinogen) of both populations were analyzed following statistic criteria. The analyzed data of this study related to oxidative stress and coagulation factors proved that the differences observed between diabetic patients and controls were not statistically significant (P statistically significant (P < 0.01). In patients with DM2, factor VIII increased from 79 to 103%, factor IX from 88 to 103%, factor XII from 87 to 105% and finally, antithrombin III from 81 to 103%. Different results between literature and our study could be due to fact that the patients considered were in the early stage of diabetes when endothelial damage is absent and vascular complications are not clinically expressed. In this study, it is still shown that DM2 is a multifactor disease and its physiopathologic mechanisms are not completely known today.

  5. Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B

    Science.gov (United States)

    Su, Jin; Zhu, Liqing; Sherman, Alexandra; Wang, Xiaomei; Lin, Shina; Kamesh, Aditya; Norikane, Joey H.; Streatfield, Stephen J.; Herzog, Roland W.; Daniell, Henry

    2015-01-01

    Antibodies (inhibitors) developed by hemophilia B patients against coagulation factor IX (FIX) are challenging to eliminate because of anaphylaxis or nephrotic syndrome after continued infusion. To address this urgent unmet medical need, FIX fused with a transmucosal carrier (CTB) was produced in a commercial lettuce (Simpson Elite) cultivar using species specific chloroplast vectors regulated by endogenous psbA sequences. CTB-FIX (~1mg/g) in lyophilized cells was stable with proper folding, disulfide bonds and pentamer assembly when stored ~2 years at ambient temperature. Feeding lettuce cells to hemophilia B mice delivered CTB-FIX efficiently to the gut immune system, induced LAP+ regulatory T cells and suppressed inhibitor/IgE formation and anaphylaxis against FIX. Lyophilized cells enabled 10-fold dose escalation studies and successful induction of oral tolerance was observed in all tested doses. Induction of tolerance in such a broad dose range should enable oral delivery to patients of different age groups and diverse genetic background. Using Fraunhofer cGMP hydroponic system, ~870 kg fresh or 43.5 kg dry weight can be harvested per 1000 ft2 per annum yielding 24,000–36,000 doses for 20-kg pediatric patients, enabling first commercial development of an oral drug, addressing prohibitively expensive purification, cold storage/transportation and short shelf life of current protein drugs. PMID:26302233

  6. Correlation between thromboelastography and traditional coagulation test parameters in hospitalized dogs

    Directory of Open Access Journals (Sweden)

    Rubanick JV

    2017-02-01

    Full Text Available Jean V Rubanick, Medora B Pashmakova, Micah A Bishop, James W Barr Department of Veterinary Small Animal Clinical Sciences, Texas A&M University, College Station, TX, USA Abstract: A hospital-based, prospective cross-sectional study was used to compare kaolin-activated thromboelastography (TEG parameters with traditional coagulation tests in 29 hospitalized dogs. Cases were included if the attending clinician requested coagulation testing. Blood was obtained from each dog and coagulation (prothrombin time, partial thromboplastin time, antithrombin activity, d-dimer concentration, and fibrinogen concentration and TEG analyses were performed. Hematocrit (Hct was also measured. Traditional coagulation results were evaluated for correlation with those from kaolin-activated TEG. Spearman’s correlation was used to calculate correlation coefficients. Fibrinogen was positively correlated with maximum amplitude (Pearson r=0.72, P<0.001 and global clot strength (Pearson r=0.72, P<0.001. There was no correlation between any of the remaining coagulation variables, TEG parameters, or Hct. Results of kaolin-activated TEG and traditional coagulation tests are not interchangeable means of monitoring coagulation derangements in this intensive care unit patient population. Determination of a true outcome measure is necessary to establish TEG’s clinical relevance to veterinary medicine. Keywords: TEG, thromboelastography, coagulation, hemostasis

  7. Bufadienolides from Kalanchoe daigremontiana as thrombin inhibitors-In vitro and in silico study.

    Science.gov (United States)

    Kolodziejczyk-Czepas, Joanna; Sieradzka, Malgorzata; Moniuszko-Szajwaj, Barbara; Pecio, Łukasz; Ponczek, Michal B; Nowak, Pawel; Stochmal, Anna

    2017-06-01

    Thrombin is an active plasma coagulation factor II, critical for the formation of fibrin clot during blood coagulation. For that reason, this protein is also a crucial target for different anti-thrombotic therapies. The work is based on in vitro evaluation of the inhibitory effect of bufadienolide-rich fraction, isolated from roots of Kalanchoe daigremontiana (1-50μg/ml) on enzymatic properties of a serine proteinase - thrombin. The efficacy of the inhibition of amidolytic activity of thrombin (measured as a hydrolysis of the chromogenic substrate S-2238, Chromogenix) attained about 10 and 66%, respectively. The IC 50 , established for the examined bufadienolide fraction was 2.79μg/ml, while the IC 50 calculated for argatroban (reference compound) was 0.78μg/ml. Linearization conducted using Lineweaver-Burk plot indicated that the K. daigremontiana fraction contains compounds that are uncompetitive inhibitors of thrombin. K. daigremontiana fraction was also able to reduce the proteolytic activity of thrombin towards its physiological substrate, i.e. fibrinogen. Additionally, this study is supported by in silico analysis of interactions of the most common compounds, identified in the examined in Kalanchoe extract to crystal structure of this enzyme. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Blood group AB and factor V Leiden as risk factors for pre-eclampsia: a population-based nested case-control study.

    Science.gov (United States)

    Hiltunen, Leena M; Laivuori, Hannele; Rautanen, Anna; Kaaja, Risto; Kere, Juha; Krusius, Tom; Paunio, Mikko; Rasi, Vesa

    2009-06-01

    Pre-eclampsia is an important cause of maternal morbidity and mortality. Its etiology is still unknown. Clinical symptoms correlate with activation of coagulation and inherited thrombophilia has been associated with pre-eclampsia. ABO blood group has been associated with thrombotic disorders and pre-eclampsia. We assessed ABO blood group, seven thrombophilia associated polymorphisms, and anti-beta2-glycoprotein I antibodies as risk factors for pre-eclampsia. We performed a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers and medical records were reviewed. We studied 248 cases fulfilling strict criteria for pre-eclampsia and 679 controls. Severe pre-eclampsia, early pre-eclampsia, and pre-eclampsia with intra-uterine growth restriction (IUGR) were analyzed separately. Blood group AB increased the risk for pre-eclampsia as a whole (OR 2.1, 95% CI 1.3-3.5), and in the three subgroups (OR 2.3, 3.8, 3.4; 95% CI 1.3-3.9, 2.0-7.1, 1.6-7.1). FV Leiden increased the risk as a whole (OR 1.7, 95% CI 0.8-3.9), and in the three subgroups, although not statistically significantly. Anti-beta2-glycoprotein I antibodies were not associated with pre-eclampsia. High body mass index, diabetes, first pregnancy, and twin pregnancy increased the risk from 1.5-fold to 8.2-fold. Our results confirm and extend the prior observation of blood group AB being a risk factor for pre-eclampsia. ABO blood group is known from all pregnant women. The value of blood group as risk factor for pre-eclampsia should be further assessed in prospective studies. In this study, FV Leiden was not statistically significant risk factor.

  9. In-vitro effects of tri-iodinated X-ray contrast media on blood coagulation, fibrinolysis and complement system

    International Nuclear Information System (INIS)

    Blanke, D.

    1982-01-01

    In-vitro experiments with Jodipamid, Jothalamat and Diatrizoat served the purpose of determining influences of contrast media on blood coagulation, fibrinolysis and the complement system. For all three contrast media investigated the effect noted was dose-dependent and was only brought about by concentrations higher than physiological ones. Liver-pathway Jodipamid was seen to have a much stronger effect than the two renal-pathway contrast media Jothalamat and Diatrizoat, which is probably due to the different protein binding capacities. In detail, the results with Jodipamid were as follows: a sharp fall in thrombinogen, a distinct decrease in fibrinogen both in the immunological and functional test, but only delayed decrease in complement factor C 4. Fibrinolytic fission products were found after applying the dose of 30 mM, as compared to 400 mM for the renal-pathway contrast media. Furthermore the functional tests (F I and F II) with Jothalamat and Diatrizoat showed only slight effects, the immunological ones (F I and C 4) none at all. The influence of the contrast media on factors I and II is interpreted by the author as an inhibition of fibrin polymerization. What seems to be the verification of fibrinolytic fission products is explained by a non-specific agglutination reaction, the decrease in C 4 by contrast-medium-induced protein denaturation. (orig./MG) [de

  10. Reincarnation of ancient links between coagulation and complement.

    Science.gov (United States)

    Conway, E M

    2015-06-01

    Throughout evolution, organisms have developed means to contain wounds by simultaneously limiting bleeding and eliminating pathogens and damaged host cells via the recruitment of innate defense mechanisms. Disease emerges when there is unchecked activation of innate immune and/or coagulation responses. A key component of innate immunity is the complement system. Concurrent excess activation of coagulation and complement - two major blood-borne proteolytic pathways - is evident in numerous diseases, including atherosclerosis, diabetes, venous thromboembolic disease, thrombotic microangiopathies, arthritis, cancer, and infectious diseases. Delineating the cross-talk between these two cascades will uncover novel therapeutic insights. © 2015 International Society on Thrombosis and Haemostasis.

  11. Massive Exploration of Perturbed Conditions of the Blood Coagulation Cascade through GPU Parallelization

    Directory of Open Access Journals (Sweden)

    Paolo Cazzaniga

    2014-01-01

    high-performance computing solutions is motivated by the need of performing large numbers of in silico analysis to study the behavior of biological systems in different conditions, which necessitate a computing power that usually overtakes the capability of standard desktop computers. In this work we present coagSODA, a CUDA-powered computational tool that was purposely developed for the analysis of a large mechanistic model of the blood coagulation cascade (BCC, defined according to both mass-action kinetics and Hill functions. coagSODA allows the execution of parallel simulations of the dynamics of the BCC by automatically deriving the system of ordinary differential equations and then exploiting the numerical integration algorithm LSODA. We present the biological results achieved with a massive exploration of perturbed conditions of the BCC, carried out with one-dimensional and bi-dimensional parameter sweep analysis, and show that GPU-accelerated parallel simulations of this model can increase the computational performances up to a 181× speedup compared to the corresponding sequential simulations.

  12. Acoustic radiation force induced resonance elastography of coagulating blood: theoretical viscoelasticity modeling and ex vivo experimentation

    Science.gov (United States)

    Bhatt, Manish; Montagnon, Emmanuel; Destrempes, François; Chayer, Boris; Kazemirad, Siavash; Cloutier, Guy

    2018-03-01

    Deep vein thrombosis is a common vascular disease that can lead to pulmonary embolism and death. The early diagnosis and clot age staging are important parameters for reliable therapy planning. This article presents an acoustic radiation force induced resonance elastography method for the viscoelastic characterization of clotting blood. The physical concept of this method relies on the mechanical resonance of the blood clot occurring at specific frequencies. Resonances are induced by focusing ultrasound beams inside the sample under investigation. Coupled to an analytical model of wave scattering, the ability of the proposed method to characterize the viscoelasticity of a mimicked venous thrombosis in the acute phase is demonstrated. Experiments with a gelatin-agar inclusion sample of known viscoelasticity are performed for validation and establishment of the proof of concept. In addition, an inversion method is applied in vitro for the kinetic monitoring of the blood coagulation process of six human blood samples obtained from two volunteers. The computed elasticity and viscosity values of blood samples at the end of the 90 min kinetics were estimated at 411  ±  71 Pa and 0.25  ±  0.03 Pa · s for volunteer #1, and 387  ±  35 Pa and 0.23  ±  0.02 Pa · s for volunteer #2, respectively. The proposed method allowed reproducible time-varying thrombus viscoelastic measurements from samples having physiological dimensions.

  13. Multiple roles of the coagulation protease cascade during virus infection.

    Science.gov (United States)

    Antoniak, Silvio; Mackman, Nigel

    2014-04-24

    The coagulation cascade is activated during viral infections. This response may be part of the host defense system to limit spread of the pathogen. However, excessive activation of the coagulation cascade can be deleterious. In fact, inhibition of the tissue factor/factor VIIa complex reduced mortality in a monkey model of Ebola hemorrhagic fever. Other studies showed that incorporation of tissue factor into the envelope of herpes simplex virus increases infection of endothelial cells and mice. Furthermore, binding of factor X to adenovirus serotype 5 enhances infection of hepatocytes but also increases the activation of the innate immune response to the virus. Coagulation proteases activate protease-activated receptors (PARs). Interestingly, we and others found that PAR1 and PAR2 modulate the immune response to viral infection. For instance, PAR1 positively regulates TLR3-dependent expression of the antiviral protein interferon β, whereas PAR2 negatively regulates expression during coxsackievirus group B infection. These studies indicate that the coagulation cascade plays multiple roles during viral infections.

  14. Blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-lacunar stroke and non-stroke: systematic review and meta-analysis.

    Science.gov (United States)

    Wiseman, Stewart; Marlborough, Fergal; Doubal, Fergus; Webb, David J; Wardlaw, Joanna

    2014-01-01

    The cause of cerebral small vessel disease is not fully understood, yet it is important, accounting for about 25% of all strokes. It also increases the risk of having another stroke and contributes to about 40% of dementias. Various processes have been implicated, including microatheroma, endothelial dysfunction and inflammation. A previous review investigated endothelial dysfunction in lacunar stroke versus mostly non-stroke controls while another looked at markers of inflammation and endothelial damage in ischaemic stroke in general. We have focused on blood markers between clinically evident lacunar stroke and other subtypes of ischaemic stroke, thereby controlling for stroke in general. We systematically assessed the literature for studies comparing blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-stroke controls or other ischaemic stroke subtypes. We assessed the quality of included papers and meta-analysed results. We split the analysis on time of blood draw in relation to the stroke. We identified 1,468 full papers of which 42 were eligible for inclusion, including 4,816 ischaemic strokes, of which 2,196 were lacunar and 2,500 non-stroke controls. Most studies subtyped stroke using TOAST. The definition of lacunar stroke varied between studies. Markers of coagulation/fibrinolysis (tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), fibrinogen, D-dimer) were higher in lacunar stroke versus non-stroke although fibrinogen was no different to non-stroke in the acute phase. tPA and PAI were no different between lacunar and non-lacunar stroke. Fibrinogen and D-dimer were significantly lower in lacunar stroke compared to other ischaemic strokes, both acutely and chronically. Markers of endothelial dysfunction (homocysteine, von Willebrand Factor (vWF), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM), vascular cellular adhesion molecule-1 (VCAM)) were higher or

  15. The Coagulation Profile of End-Stage Liver Disease and Considerations for Intraoperative Management.

    Science.gov (United States)

    Forkin, Katherine T; Colquhoun, Douglas A; Nemergut, Edward C; Huffmyer, Julie L

    2018-01-01

    The coagulopathy of end-stage liver disease results from a complex derangement in both anticoagulant and procoagulant processes. With even minor insults, cirrhotic patients experience either inappropriate bleeding or clotting, or even both simultaneously. The various phases of liver transplantation along with fluid and blood product administration may contribute to additional disturbances in coagulation. Thus, anesthetic management of patients undergoing liver transplantation to improve hemostasis and avoid inappropriate thrombosis in the perioperative environment can be challenging. To add to this challenge, traditional laboratory tests of coagulation are difficult to interpret in patients with end-stage liver disease. Viscoelastic coagulation tests such as thromboelastography (Haemonetics Corporation, Braintree, MA) and rotational thromboelastometry (TEM International, Munich, Germany) have helped to reduce transfusion of allogeneic blood products, especially fresh frozen plasma, but have also lead to the increased use of fibrinogen-containing products. In general, advancements in surgical techniques and anesthetic management have led to significant reduction in blood transfusion requirements during liver transplantation. Targeted transfusion protocols and pharmacologic prevention of fibrinolysis may further aid in the management of the complex coagulopathy of end-stage liver disease.

  16. Ex-vivo response to blood products and haemostatic agents after paediatric cardiac surgery

    DEFF Research Database (Denmark)

    Hvas, Anne-Mette; Andreasen, Jo B; Christiansen, Kirsten

    2013-01-01

    cardiac surgery. The haemostatic potential of various factor concentrates (fibrinogen concentrate, recombinant factor VIIa and factor XIII), fresh frozen plasma (FFP), pooled platelets and tranexamic acid was investigated. After surgery, the coagulation profiles revealed significantly prolonged clotting...... of fibrinogen concentrate, FFP or tranexamic acid improved clot stability significantly. Whole blood coagulation was significantly impaired after cardiac surgery in children. Ex-vivo studies showed a total reversal of the coagulopathy after addition of pooled platelets and significantly improved clot stability...... after addition of fibrinogen concentrate, FFP and tranexamic acid, respectively....

  17. First report of real-time monitoring of coagulation function potential and IgG subtype of anti-FVIII autoantibodies in a child with acquired hemophilia A associated with streptococcal infection and amoxicillin.

    Science.gov (United States)

    Takeyama, Masahiro; Nogami, Keiji; Kajimoto, Takahiro; Ogiwara, Kenichi; Matsumoto, Tomoko; Shima, Midori

    2018-01-01

    We describe an 8-year-old boy with acquired hemophilia A (AHA) associated with streptococcal infection and amoxicillin. Laboratory data revealed low factor VIII activity (FVIII:C, 1.5 IU/dl), and FVIII inhibitor (15.9 BU/ml). Comprehensive coagulation function assays, including rotation thromboelastometry (ROTEM ® ), revealed a markedly prolonged clotting time. Thrombin and plasmin generation (TG/PG) appeared to be moderately impaired. The inhibitor epitope of his anti-FVIII autoantibody recognized light and heavy chains. He was treated with Novoseven ® and prednisolone, resulting in rapid improvement. ROTEM showed the return of coagulation time to normal level on day 20, and TG gradually improved. PG was moderately reduced in the clinical early phase, but improved at day 20. The patient's IgG subtype was IgG 4 at onset. IgG 1 was transiently positive on day 20, but negative on day 46. FVIII inhibitor gradually decreased and was completely absent after day 46, along with the elevated FVIII:C. IgG4 was again elevated on day 83, followed by a rapid decrease, indicative of the presence of non-neutralizing antibody, which remains currently undetected. We for the first time report changes in comprehensive coagulation function and IgG subtype of anti-FVIII antibody in a rare pediatric case of AHA.

  18. Kinetics of the Factor XIa catalyzed activation of human blood coagulation Factor IX

    International Nuclear Information System (INIS)

    Walsh, P.N.; Bradford, H.; Sinha, D.; Piperno, J.R.; Tuszynski, G.P.

    1984-01-01

    The kinetics of activation of human Factor IX by human Factor XIa was studied by measuring the release of a trichloroacetic acid-soluble tritium-labeled activation peptide from Factor IX. Initial rates of trichloroacetic acid-soluble 3 H-release were linear over 10-30 min of incubation of Factor IX (88 nM) with CaCl 2 (5 mM) and with pure (greater than 98%) Factor XIa (0.06-1.3 nM), which was prepared by incubating human Factor XI with bovine Factor XIIa. Release of 3 H preceded the appearance of Factor IXa activity, and the percentage of 3 H released remained constant when the mole fraction of 3 H-labeled and unlabeled Factor IX was varied and the total Factor IX concentration remained constant. A linear correlation (r greater than 0.98, P less than 0.001) was observed between initial rates of 3 H-release and the concentration of Factor XIa, measured by chromogenic assay and by radioimmunoassay and added at a Factor IX:Factor XIa molar ratio of 70-5,600. Kinetic parameters, determined by Lineweaver-Burk analysis, include K/sub m/ (0.49 microM) of about five- to sixfold higher than the plasma Factor IX concentration, which could therefore regulate the reaction. The catalytic constant (k/sub cat/) (7.7/s) is approximately 20-50 times higher than that reported by Zur and Nemerson for Factor IX activation by Factor VIIa plus tissue factor. Therefore, depending on the relative amounts of Factor XIa and Factor VIIa generated in vivo and other factors which may influence reaction rates, these kinetic parameters provide part of the information required for assessing the relative contributions of the intrinsic and extrinsic pathways to Factor IX activation, and suggest that the Factor XIa catalyzed reaction is physiologically significant

  19. [Evaluation of selected parameters of blood coagulation and fibrinolysis system in patients undergoing total hip replacement surgery with normovolemic hemodilution procedure and standard enoxaparine prophylaxis].

    Science.gov (United States)

    Piecuch, Wiesław; Sokołowska, Bozena; Dmoszyńska, Anna; Furmanik, Franciszek

    2003-01-01

    The aim of the study was to evaluate selected blood coagulation and fibrinolysis parameters in patients undergoing total hip replacement surgery with normovolemic hemodilution and standard enoksaparine profilaxis. The study included 66 patients undergoing hip replacement surgery. The group consisted of 51 women and 15 men, within the age range of 47-78, the mean age was 64. In 32 (subgroup II) patients the surgery was performed with the use of normovolemic hemodilution, in 34 (subgroup I) the hemodilution procedure was not applied. The enoksaparine as prophylaxis started 12 hours prior to surgery and continued during hospitalisation. The examination of the coagulation system was performed: on the day of the operation in the morning, on the day of the operation in the evening and on the first day after operation. We determined the concentrations of TAT and PAP complexes, prothrombin fragments 1 + 2 (F1 + 2) and d-dimers (DD). 1) during total hip replacement surgery and particularly in the period of the first 12 hours after the procedure marked activation of coagulation and fibrinolysis occurRed; 2) the application of the hemodilution procedure does not influence significantly the degree of coagulation and fibrinolysis disorders in the perioperative period, but could reduced incidence of thromboembolic complications in the postoperative period.

  20. Bladder perforation owing to a unipolar coagulating device.

    Science.gov (United States)

    Pakter, J; Budnick, L D

    1981-09-15

    A report on a patient who sustained a burn and perforation of the urinary bladder from visible sparks emanating from a unipolar coagulating device during the couse of laparoscopic sterilization is presented. It is the first report of urinary bladder burns using a unipolar coagulating device. A 24-year-old woman, gravida 10, para 3, abortus 7, underwent a laparoscopic sterilization with a unipolar coagulating device. As the physician was finishing the coagulation, a spark from the device caused a 1-2 cm burn with a central area of perforation into the urinary bladder. Conservative treatment was recommended, and consisted of Foley catheterization and drainage for 5 days. Initial urine culture revealed Klebsiella species, and oral ampicillin was prescribed. Hematuria was noted throughout the patient's hospitalization, and blood clots were present in the urine on Day 2 postoperation. The patient had no abdominal or flank pain, was afebrile, and had a stable hemoglobin level during the hospital stay. Cystography was performed on Day 5 postoperatively and demonstrated no perforation. Foley catheter was removed. Patient was discharged 2 days later and remains in good health 3 months postoperatively.

  1. Tissue factor pathway inhibitor in paediatric patients with nephrotic ...

    African Journals Online (AJOL)

    elevated TFPI blood levels could therefore be accounted for by excessive endothelial release of this inhibitor .... that diastolic blood pressure was higher in the proteinuria group than in either the remission or the control .... dilated veins around the umbilicus, renal biopsy findings of fibrin deposition inside the glomeruli and in ...

  2. Coagulation factor VIIa-mediated protease-activated receptor 2 activation leads to β-catenin accumulation via the AKT/GSK3β pathway and contributes to breast cancer progression.

    Science.gov (United States)

    Roy, Abhishek; Ansari, Shabbir A; Das, Kaushik; Prasad, Ramesh; Bhattacharya, Anindita; Mallik, Suman; Mukherjee, Ashis; Sen, Prosenjit

    2017-08-18

    Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most common causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer-associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well established that, apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive. To this end, we investigated FVIIa's role in the migration and invasiveness of the breast cancer cell line MDA-MB-231. Consistent with previous observations, we observed that FVIIa increased the migratory and invasive potential of these cells. We also provide molecular evidence that protease-activated receptor 2 activation followed by PI3K-AKT activation and GSK3β inactivation is involved in these processes and that β-catenin, a well known tumor-regulatory protein, contributes to this signaling pathway. The pivotal role of β-catenin was further indicated by the up-regulation of its downstream targets cyclin D1, c-Myc, COX-2, MMP-7, MMP-14, and Claudin-1. β-Catenin knockdown almost completely attenuated the FVIIa-induced enhancement of breast cancer migration and invasion. These findings provide a new perspective to counteract the invasive behavior of breast cancer, indicating that blocking PI3K-AKT pathway-dependent β-catenin accumulation may represent a potential therapeutic approach to control breast cancer. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Coagulation profile of children with sickle cell anemia in steady state ...

    African Journals Online (AJOL)

    Background: Sickle cell anemia is associated with a hypercoagulable state that may lead to alterations in a coagulation profile. Measurements of coagulation factors are known to have some predictive value for clinical outcome. Objectives: To determine the coagulation profile of children with SCA in steady state and crisis ...

  4. Strategies to reduce blood product utilization in obstetric practice.

    Science.gov (United States)

    Neb, Holger; Zacharowski, Kai; Meybohm, Patrick

    2017-06-01

    Patient blood management (PBM) aims to improve patient outcome and safety by reducing the number of unnecessary RBC transfusions and vitalizing patient-specific anemia reserves. Although PBM is increasingly recognized as best clinical practice in elective surgery, implementation of PBM is restrained in the setting of obstetrics. This review summarizes recent findings to reduce blood product utilization in obstetric practice. PBM-related evidence-based benefits should be urgently adopted in the field of obstetric medicine. Intravenous iron can be considered a safe, effective strategy to replenish iron stores and to correct both pregnancy-related and hemorrhage-related iron deficiency anemia. In addition to surgical techniques and the use of uterotonics, recent findings support early administration of tranexamic acid, fibrinogen and a coagulation factor concentrate-based, viscoelastically guided practice in case of peripartum hemorrhage to manage coagulopathy. In patients with cesarean section, autologous red cell blood salvage may reduce blood product utilization, although its use in this setting is controversial. Implementation of PBM in obstetric practice offers large potential to reduce blood loss and transfusion requirements of allogeneic blood products, even though large clinical trials are lacking in this specific field. Intravenous iron supplementation may be suggested to increase peripartum hemoglobin levels. Additionally, tranexamic acid and point-of-care-guided supplementation of coagulation factors are potent methods to reduce unnecessary blood loss and blood transfusions in obstetrics.

  5. Structural characterization of coagulant Moringa oleifera Lectin and its effect on hemostatic parameters.

    Science.gov (United States)

    Luz, Luciana de Andrade; Silva, Mariana Cristina Cabral; Ferreira, Rodrigo da Silva; Santana, Lucimeire Aparecida; Silva-Lucca, Rosemeire Aparecida; Mentele, Reinhard; Oliva, Maria Luiza Vilela; Paiva, Patricia Maria Guedes; Coelho, Luana Cassandra Breitenbach Barroso

    2013-07-01

    Lectins are carbohydrate recognition proteins. cMoL, a coagulant Moringa oleifera Lectin, was isolated from seeds of the plant. Structural studies revealed a heat-stable and pH resistant protein with 101 amino acids, 11.67 theoretical pI and 81% similarity with a M. oleifera flocculent protein. Secondary structure content was estimated as 46% α-helix, 12% β-sheets, 17% β-turns and 25% unordered structures belonging to the α/β tertiary structure class. cMoL significantly prolonged the time required for blood coagulation, activated partial thromboplastin (aPTT) and prothrombin times (PT), but was not so effective in prolonging aPTT in asialofetuin presence. cMoL acted as an anticoagulant protein on in vitro blood coagulation parameters and at least on aPTT, the lectin interacted through the carbohydrate recognition domain. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B.

    Science.gov (United States)

    Su, Jin; Zhu, Liqing; Sherman, Alexandra; Wang, Xiaomei; Lin, Shina; Kamesh, Aditya; Norikane, Joey H; Streatfield, Stephen J; Herzog, Roland W; Daniell, Henry

    2015-11-01

    Antibodies (inhibitors) developed by hemophilia B patients against coagulation factor IX (FIX) are challenging to eliminate because of anaphylaxis or nephrotic syndrome after continued infusion. To address this urgent unmet medical need, FIX fused with a transmucosal carrier (CTB) was produced in a commercial lettuce (Simpson Elite) cultivar using species specific chloroplast vectors regulated by endogenous psbA sequences. CTB-FIX (∼1 mg/g) in lyophilized cells was stable with proper folding, disulfide bonds and pentamer assembly when stored ∼2 years at ambient temperature. Feeding lettuce cells to hemophilia B mice delivered CTB-FIX efficiently to the gut immune system, induced LAP(+) regulatory T cells and suppressed inhibitor/IgE formation and anaphylaxis against FIX. Lyophilized cells enabled 10-fold dose escalation studies and successful induction of oral tolerance was observed in all tested doses. Induction of tolerance in such a broad dose range should enable oral delivery to patients of different age groups and diverse genetic background. Using Fraunhofer cGMP hydroponic system, ∼870 kg fresh or 43.5 kg dry weight can be harvested per 1000 ft(2) per annum yielding 24,000-36,000 doses for 20-kg pediatric patients, enabling first commercial development of an oral drug, addressing prohibitively expensive purification, cold storage/transportation and short shelf life of current protein drugs. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Cardiopulmonary Bypass and Blood Transfusion (Indications and Problems in Tranfusion of Blood Components as of 1986)

    OpenAIRE

    金沢, 宏; 大関, 一; 矢沢, 正知; 江口, 昭治; Kanazawa, Hiroshi; Oozeki, Hajime; Yazawa, Masatomo; Eguchi, Shoji

    1987-01-01

    Cardiopulmonary bypass (CPB), functioning as the pumping system and the gas exchange functions, is one of the important instruments in cardiovascular operations. But it has many unfavourable problems such as massive blood transfusion, hemodilution, abnormality of coagulation, etc. In fact, 5 or 6 units of blood are necessary to prime CPB in infant, child, and adult. After CPB, massive blood transfusion is necessary to keep good circulation, and to recover from hemodilution and abnormal coagul...

  8. Expression and fast preparation of biologically active recombinant human coagulation factor VII in CHO-K1 cells.

    Science.gov (United States)

    Xiao, W; Li, C Q; Xiao, X P; Lin, F Z

    2013-12-16

    Human coagulation factor VII (FVII) plays an important role in the blood coagulation process and exists in micro amounts in human plasma; therefore, any attempt at the large-scale production of FVII in significant quantities is challenging. The purpose of this study was to express and obtain biologically active recombinant FVII (rFVII) from Chinese hamster ovary K1 (CHO-K1) cells. The full-length FVII cDNA was isolated from a HepG2 cell line and then subcloned in pcDNA3.1 to construct an expression vector, pcDNA-FVII. CHO-K1 cells were transfected with 1 µg pcDNA-FVII. The cell line that stably expressed secretory FVII was screened using 900 µg/mL G418. The FVII copy number in CHO-K1 cells was detected by quantitative polymerase chain reaction (qPCR). The rFVII was purified in ligand affinity chromatography medium. The purified protein was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis. The biological activity of the purified FVII protein was determined by a prothrombin time assay. Three cell lines that permanently expressed rFVII were screened. The qPCR results demonstrated that each CHO-K1 cell harbored two FVII DNA copies. The SDS-PAGE and Western blot analysis showed that the purified protein was about 50 kDa. The purity of the target protein was 95%. The prothrombin time assay indicated that the FVII-specific activity of rFVII was 2573 ± 75 IU/mg. This method enabled the fast preparation of high-purity rFVII from CHO-K1 cells, and the purified protein had good biological activity.

  9. Early activation of the coagulation system during lower body negative pressure

    DEFF Research Database (Denmark)

    Zaar, M; Johansson, P I; Nielsen, L B

    2009-01-01

    We considered that a moderate reduction of the central blood volume (CBV) may activate the coagulation system. Lower body negative pressure (LBNP) is a non-invasive means of reducing CBV and, thereby, simulates haemorrhage. We tested the hypothesis that coagulation markers would increase following...... moderate hypovolemia by exposing 10 healthy male volunteers to 10 min of 30 mmHg LBNP. Thoracic electrical impedance increased during LBNP (by 2.6 +/- 0.7 Omega, mean +/- SD; P pressure decreased (84 +/- 5 to 80...

  10. Impact of Silver Nanoparticles on Haemolysis, Platelet Function and Coagulation

    Directory of Open Access Journals (Sweden)

    Julie Laloy

    2014-09-01

    Full Text Available Silver nanoparticles (Ag NPs are increasingly used in biomedical applications because of their large antimicrobial spectrum. Data in the literature on the ability of Ag NPs to perform their desired function without eliciting undesirable effects on blood elements are very limited and contradictory. We studied the impact of Ag NPs on erythrocyte integrity, platelet function and blood coagulation. Erythrocyte integrity was assessed by spectrophotometric measurement of haemoglobin release. Platelet adhesion and aggregation was determined by light transmission aggregometry and scanning electron microscopy. The calibrated thrombin generation test was used to study the impact on coagulation cascade. We demonstrated that Ag NPs induced haemolysis. They also increase platelet adhesion without having any impact on platelet aggregation. Finally, they also had procoagulant potential. Bringing all data from these tests together, the no observed effect concentration is 5 μg/mL.

  11. Discovery of natural mouse serum derived HIV-1 entry inhibitor(s).

    Science.gov (United States)

    Wei, M; Chen, Y; Xi, J; Ru, S; Ji, M; Zhang, D; Fang, Q; Tang, B

    Among rationally designed human immunodeficiency virus 1 (HIV-1) inhibitors, diverse natural factors have showed as potent anti-HIV activity in human blood. We have discovered that the boiled supernatant of healthy mouse serum could suppress HIV-1 entry, and exhibited reduced inhibitory activity after trypsin digestion. Further analysis demonstrated that only the fraction containing 10-25 K proteins could inhibit HIV-1 mediated cell-cell fusion. These results suggest that the 10-25 K protein(s) is novel natural HIV-1 entry inhibitor(s). Our findings provide important information about novel natural HIV entry inhibitors in mouse serum.

  12. Investigation of coagulation activity of natural coagulants from seeds of different leguminose species

    Directory of Open Access Journals (Sweden)

    Šćiban Marina B.

    2005-01-01

    Full Text Available The ability of seeds of plants: Phaseolus vulgaris, Robinia pseudoacacia Ceratonia siliqua and Amorpha fruticosa, to act as natural coagulants was tested using synthetic turbid water. This water was prepared by adding kaolin into tap water, just before the test. Active components were extracted from ground seeds with distilled water. The coagulation ability of this extract was assessed by the use of standard jar test measurements in water with various initial turbidity. Investigation of these natural coagulants was confirmed their positive coagulation activity. Of all plants that have been examined, the seed extract from Ceratonia siliqua appeared to be one of the most effective coagulants for water treatment. A dose of 20 mg/l of this coagulant resulted in 100% coagulation activity for clarification of water with 17.5 NTU initial turbidity.

  13. Whole blood coagulation and platelet activation in the athlete: A comparison of marathon, triathlon and long distance cycling

    Directory of Open Access Journals (Sweden)

    Hanke AA

    2010-02-01

    Full Text Available Abstract Introduction Serious thrombembolic events occur in otherwise healthy marathon athletes during competition. We tested the hypothesis that during heavy endurance sports coagulation and platelets are activated depending on the type of endurance sport with respect to its running fraction. Materials and Methods 68 healthy athletes participating in marathon (MAR, running 42 km, n = 24, triathlon (TRI, swimming 2.5 km + cycling 90 km + running 21 km, n = 22, and long distance cycling (CYC, 151 km, n = 22 were included in the study. Blood samples were taken before and immediately after completion of competition to perform rotational thrombelastometry. We assessed coagulation time (CT, maximum clot firmness (MCF after intrinsically activation and fibrin polymerization (FIBTEM. Furthermore, platelet aggregation was tested after activation with ADP and thrombin activating peptide 6 (TRAP by using multiple platelet function analyzer. Results Complete data sets were obtained in 58 athletes (MAR: n = 20, TRI: n = 19, CYC: n = 19. CT significantly decreased in all groups (MAR -9.9%, TRI -8.3%, CYC -7.4% without differences between groups. In parallel, MCF (MAR +7.4%, TRI +6.1%, CYC +8.3% and fibrin polymerization (MAR +14.7%, TRI +6.1%, CYC +8.3% were significantly increased in all groups. However, platelets were only activated during MAR and TRI as indicated by increased AUC during TRAP-activation (MAR +15.8% and increased AUC during ADP-activation in MAR (+50.3% and TRI (+57.5%. Discussion While coagulation is activated during physical activity irrespective of type we observed significant platelet activation only during marathon and to a lesser extent during triathlon. We speculate that prolonged running may increase platelet activity, possibly, due to mechanical alteration. Thus, particularly prolonged running may increase the risk of thrombembolic incidents in running athletes.

  14. Whole blood coagulation and platelet activation in the athlete: a comparison of marathon, triathlon and long distance cycling.

    Science.gov (United States)

    Hanke, Alexander A; Staib, A; Görlinger, K; Perrey, M; Dirkmann, D; Kienbaum, P

    2010-02-26

    Serious thrombembolic events occur in otherwise healthy marathon athletes during competition. We tested the hypothesis that during heavy endurance sports coagulation and platelets are activated depending on the type of endurance sport with respect to its running fraction. 68 healthy athletes participating in marathon (MAR, running 42 km, n = 24), triathlon (TRI, swimming 2.5 km + cycling 90 km + running 21 km, n = 22), and long distance cycling (CYC, 151 km, n = 22) were included in the study. Blood samples were taken before and immediately after completion of competition to perform rotational thrombelastometry. We assessed coagulation time (CT), maximum clot firmness (MCF) after intrinsically activation and fibrin polymerization (FIBTEM). Furthermore, platelet aggregation was tested after activation with ADP and thrombin activating peptide 6 (TRAP) by using multiple platelet function analyzer. Complete data sets were obtained in 58 athletes (MAR: n = 20, TRI: n = 19, CYC: n = 19). CT significantly decreased in all groups (MAR -9.9%, TRI -8.3%, CYC -7.4%) without differences between groups. In parallel, MCF (MAR +7.4%, TRI +6.1%, CYC +8.3%) and fibrin polymerization (MAR +14.7%, TRI +6.1%, CYC +8.3%) were significantly increased in all groups. However, platelets were only activated during MAR and TRI as indicated by increased AUC during TRAP-activation (MAR +15.8%) and increased AUC during ADP-activation in MAR (+50.3%) and TRI (+57.5%). While coagulation is activated during physical activity irrespective of type we observed significant platelet activation only during marathon and to a lesser extent during triathlon. We speculate that prolonged running may increase platelet activity, possibly, due to mechanical alteration. Thus, particularly prolonged running may increase the risk of thrombembolic incidents in running athletes.

  15. Vitamin K: the effect on health beyond coagulation – an overview

    Directory of Open Access Journals (Sweden)

    Cees Vermeer

    2012-04-01

    Full Text Available Vitamin K is essential for the synthesis of proteins belonging to the Gla-protein family. To the members of this family belong four blood coagulation factors, which all are exclusively formed in the liver. The importance of vitamin K for hemostasis is demonstrated from the fact that vitamin K-deficiency is an acute, life-threatening condition due to excessive bleeding. Other members of the Gla-protein family are osteocalcin, matrix Gla-protein (MGP, and Gas6 that play key functions in maintaining bone strength, arterial calcification inhibition, and cell growth regulation, respectively. In total 17 Gla-proteins have been discovered at this time. Recently, it was observed that the dietary vitamin K requirement for the synthesis of the coagulation factors is much lower than for that of the extra-hepatic Gla-proteins. This forms the basis of the triage theory stating that during poor dietary supply, vitamins are preferentially utilized for functions that are important for immediate survival. This explains why in the healthy population all clotting factors are synthesized in their active form, whereas the synthesis of other Gla-proteins is sub-optimal in non-supplemented subjects. Prolonged sub-clinical vitamin K deficiency is a risk factor for osteoporosis, atherosclerosis, and cancer. Present recommendations for dietary intake are based on the daily dose required to prevent bleeding. Accumulating scientific data suggests that new, higher recommendations for vitamin K intake should be formulated.

  16. Molecular cloning, characterization and expression analysis of coagulation factor VII gene in grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Liu, Qiaolin; Xu, Baohong; Xiao, Tiaoyi; Su, Jianming; Zhong, Lei

    2013-08-01

    Coagulation factor VII has been studied in several species but, to date, not in grass carp (Ctenopharyngodon idella), a commercially important freshwater fish found in China. In this study, the full-length cDNA of grass carp coagulation factor VII (GcCFVII) was cloned using a RACE-Ready cDNA Kit, grass carp were challenged with a hemorrhagic virus, and temporal expression profiles of GcCFVII in the thymus, gills, liver, spleen, and head kidney were examined at 0 h, 24 h, 48 h, 72 h, 96 h, and 138 h using fluorescence quantitative PCR. The results showed the 1480 bp GcCFVII to contain three conservative motifs: Gla, EGF-CA, and Tryp-SPc, similar to other species. Phylogenetic analysis showed the evolution of GcCFVII gene to be consistent with the evolution of the species. After viral challenge, GcCFVII expression in five tissues of grass carp showed different patterns of fluctuation. These results provide a solid basis for further investigation of GcCFVII and its relationship with grass carp hemorrhage. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Comparison of coagulation activity tests in vitro for selected biomaterials

    NARCIS (Netherlands)

    van Oeveren, W; Haan, J; Lagerman, P; Schoen, T

    Testing of coagulation induced by external communicating medical devices is an International Standardisation Organization (ISO) requirement for products exposed to human blood. Four categories of tests are indicated by ISO 10993/4: a clotting test (partial thromboplastin time; PTT), thrombin

  18. Impact of Albumin on Coagulation Competence and Hemorrhage During Major Surgery

    DEFF Research Database (Denmark)

    Rasmussen, Kirsten C; Højskov, Michael; Johansson, Pär I.

    2016-01-01

    trial evaluates whether administration of 5% human albumin (HA) or lactated Ringer solution (LR) affects coagulation competence and in turn blood loss during cystectomy due to bladder cancer. Forty patients undergoing radical cystectomy were included to receive either 5% HA (n = 20) or LR (n = 20......). Nineteen patients were analyzed in the HA group and 20 patients in the lactated Ringer group. Blinded determination of the blood loss was similar in the 2 groups of patients: 1658 (800-3300) mL with the use of HA and 1472 (700-4330) mL in the lactated Ringer group (P = 0.45). Yet, by thrombelastography...... (TEG) evaluated coagulation competence, albumin affected clot growth (TEG-angle 69 ± 5 vs 74° ± 3°, P 

  19. Extracellular Histones Increase Tissue Factor Activity and Enhance Thrombin Generation by Human Blood Monocytes.

    Science.gov (United States)

    Gould, Travis J; Lysov, Zakhar; Swystun, Laura L; Dwivedi, Dhruva J; Zarychanski, Ryan; Fox-Robichaud, Alison E; Liaw, Patricia C

    2016-12-01

    Sepsis is characterized by systemic activation of inflammatory and coagulation pathways in response to infection. Recently, it was demonstrated that histones released into the circulation by dying/activated cells may contribute to sepsis pathology. Although the ability of extracellular histones to modulate the procoagulant activities of several cell types has been investigated, the influence of histones on the hemostatic functions of circulating monocytes is unknown. To address this, we investigated the ability of histones to modulate the procoagulant potential of THP-1 cells and peripheral blood monocytes, and examined the effects of plasmas obtained from septic patients to induce a procoagulant phenotype on monocytic cells. Tissue factor (TF) activity assays were performed on histone-treated THP-1 cells and blood monocytes. Exposure of monocytic cells to histones resulted in increases in TF activity, TF antigen, and phosphatidylserine exposure. Histones modulate the procoagulant activity via engagement of Toll-like receptors 2 and 4, and this effect was abrogated with inhibitory antibodies. Increased TF activity of histone-treated cells corresponded to enhanced thrombin generation in plasma determined by calibrated automated thrombography. Finally, TF activity was increased on monocytes exposed to plasma from septic patients, an effect that was attenuated in plasma from patients receiving unfractionated heparin (UFH). Our studies suggest that increased levels of extracellular histones found in sepsis contribute to dysregulated coagulation by increasing TF activity of monocytes. These procoagulant effects can be partially ameliorated in sepsis patients receiving UFH, thereby identifying extracellular histones as a potential therapeutic target for sepsis treatment.

  20. [Warming acupuncture combined with conventional acupuncture for diabetic peripheral neuropathy with syndrome of yang deficiency and cold coagulation, obstruction of collaterals and blood stasis].

    Science.gov (United States)

    Ma, Guoqing; Ye, Ting; Sun, Zhongren

    2018-03-12

    To compare the clinical efficacy differences between warming acupuncture and conventional acupuncture for diabetic peripheral neuropathy (DPN) with syndrome of yang deficiency and cold coagulation, obstruction of collaterals and blood stasis. A total of 64 patients were randomly divided into a warming acupuncture group and a conventional acupuncture group, 32 cases in each one. Based on basic treatment of blood glucose regulation, warming acupuncture was applied at Pishu (BL 20), Shenshu (BL 23), Guanyuanshu (BL 26), Zusanli (ST 36), Chongyang (ST 42), Quchi (LI 11) and Hegu (LI 4) in the warming acupuncture group, while acupuncture was applied at the identical acupoints in the conventional acupuncture group. Both the treatments were given once a day with an interval of one day every six days; totally the treatment was given for 4 weeks. The TCM symptom score, Toronto clinical scoring system (TCSS) and nerve conduction velocity (NCV) before and after treatment were compared in the two groups. After treatment, the TCM symptom scores in the two groups were significantly reduced (both P nervus peroneus communis, as well as sensory nerve of tibial nerve and sural nerve was improved in the warming acupuncture group (all P 0.05). Warming acupuncture and conventional acupuncture could both increase TCM symptom score, improve NCV in patients of DPN with syndrome of yang deficiency and cold coagulation, obstruction of collaterals and blood stasis; warming acupuncture has advantage in symptom improvement.

  1. IMPROVEMENT OF COAGULATION PROCESS FOR THE PRUT RIVER WATER TREATMENT USING ALUMINUM SULPHATE

    Directory of Open Access Journals (Sweden)

    Larisa Postolachi

    2015-06-01

    Full Text Available The aim of presented research was to optimize the treatment process of the Prut River water. In order to realize the proposed goal, there were studied the following factors which can improve the process of coagulation: (i the influence of stirring speed during coagulation and (ii the influence of the concentration of the coagulant solution added in the process of coagulation. The optimal conditions of coagulation were established using the Jar-test method. Application of the recommended procedure contribute to the reduction of the coagulant dose, the contact time, the aluminum concentration in water and the expenses for water treatment.

  2. Red blood cell-derived microparticles isolated from blood units initiate and propagate thrombin generation.

    Science.gov (United States)

    Rubin, Olivier; Delobel, Julien; Prudent, Michel; Lion, Niels; Kohl, Kid; Tucker, Erik I; Tissot, Jean-Daniel; Angelillo-Scherrer, Anne

    2013-08-01

    Red blood cell-derived microparticles (RMPs) are small phospholipid vesicles shed from RBCs in blood units, where they accumulate during storage. Because microparticles are bioactive, it could be suggested that RMPs are mediators of posttransfusion complications or, on the contrary, constitute a potential hemostatic agent. This study was performed to establish the impact on coagulation of RMPs isolated from blood units. Using calibrated automated thrombography, we investigated whether RMPs affect thrombin generation (TG) in plasma. We found that RMPs were not only able to increase TG in plasma in the presence of a low exogenous tissue factor (TF) concentration, but also to initiate TG in plasma in absence of exogenous TF. TG induced by RMPs in the absence of exogenous TF was neither affected by the presence of blocking anti-TF nor by the absence of Factor (F)VII. It was significantly reduced in plasma deficient in FVIII or F IX and abolished in FII-, FV-, FX-, or FXI-deficient plasma. TG was also totally abolished when anti-XI 01A6 was added in the sample. Finally, neither Western blotting, flow cytometry, nor immunogold labeling allowed the detection of traces of TF antigen. In addition, RMPs did not comprise polyphosphate, an important modulator of coagulation. Taken together, our data show that RMPs have FXI-dependent procoagulant properties and are able to initiate and propagate TG. The anionic surface of RMPs might be the site of FXI-mediated TG amplification and intrinsic tenase and prothrombinase complex assembly. © 2012 American Association of Blood Banks.

  3. Network-Based Biomarkers for Cold Coagulation Blood Stasis Syndrome and the Therapeutic Effects of Shaofu Zhuyu Decoction in Rats

    Directory of Open Access Journals (Sweden)

    Shulan Su

    2013-01-01

    Full Text Available In this study, the reverse docking methodology was applied to predict the action targets and pathways of Shaofu Zhuyu decoction (SFZYD bioactive ingredients. Furthermore, Traditional Chinese Medicine (TCM cold coagulation blood stasis (CCBS syndrome was induced in female Sprague-Dawley rats with an ice-water bath and epinephrine, and SFZYD was used to treat CCBS syndrome. A metabolomic approach was used to evaluate changes in the metabolic profiles and to analyze the pharmacological mechanism of SFZYD actions. Twenty-three potential protein targets and 15 pathways were discovered, respectively; among these, pathways are associated with inflammation and immunological stress, hormone metabolism, coagulation function, and glycometabolism. There were also changes in the levels of endogenous metabolites of LysoPCs and glucuronides. Twenty endogenous metabolites were identified. Furthermore, the relative quantities of 6 endogenous metabolites in the plasma and 5 in the urine were significantly affected by SFZYD (P<0.05. The pharmacological mechanism of SFZYD was partially associated with glycerophospholipid metabolism and pentose and glucuronate interconversions. In conclusion, our findings demonstrated that TCM CCBS pattern induced by ice water and epinephrine was complex and related to multiple metabolic pathways. SFZYD did regulate the TCM CCBS by multitargets, and biomarkers and SFZYD should be used for the clinical treatment of CCBS syndrome.

  4. The effects of three factor VII polymorphisms on factor VII coagulant levels in healthy Singaporean Chinese, Malay and Indian newborns.

    Science.gov (United States)

    Quek, S C; Low, P S; Saha, N; Heng, C K

    2006-11-01

    Factor VII (FVII) is an independent risk factor for coronary artery disease. Three polymorphisms of the factor VII gene (F7) were studied in a group of healthy newborns comprising 561 Chinese, 398 Malays and 226 Asian Indians from Singapore. The allele frequencies of 3 polymorphisms (R353Q, Promoter 0/10bp Del/Ins and Intron 7) in the FVII gene were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. In Chinese the minor allele frequencies are Q: 0.04, Ins: 0.03, R7: 0.44; Malays, Q: 0.06, Ins: 0.10, R7: 0.41; and Indians, Q: 0.25, Ins: 0.23, R7: 0.43. Strong linkage disequilibrium (Delta > 0.7) is observed between the 0/10 bp and the R353Q sites in all ethnic groups. We conclude that: (i) the prevalence of the minor Q and Ins alleles of the R353Q and 0/10 bp polymorphisms are significantly higher in the Indian newborns than the Chinese and Malays; (ii) the Q allele is significantly associated (p = 0.01) with a lower plasma FVII coagulant level in the Indian and Malay neonates; and this polymorphism explains up to 3.8% of the variance in FVII coagulant levels; (iii) there is no significant difference in allele frequencies of the three polymorphisms between neonates with and without family histories of CAD.

  5. [Haplotype Analysis of Coagulation Factor VII Gene in a Patient with Congenital Coagulation Factor VII Deficiency with Heterozygous p.Arg337Cys Mutation and o.Aro413Gin Polymorphism..

    Science.gov (United States)

    Suzuki, Keijiro; Yoshioka, Tomoko; Obara, Takehiro; Suwabe, Akira

    2016-05-01

    Congenital coagulation factor VII (FVII) deficiency is a rare hemorrhagic disease with an autosomal reces- sive inheritance pattern. We analyzed coagulation factor VII gene (F7) of a patient with FVII deficiency and used expression studies to investigate the effect of a missense mutation on FVII secretion. The proband, a 69-year-old Japanese woman, had a history of postpartum bleeding and excessive bleeding after dental extrac- tion. She was found to have mildly increased PT-INR (1.17) before an ophthalmic operation. FVII activity and antigen were reduced (29.0% and 32.8%). Suspecting that the proband was FVII deficient, we analyzed F7 of the patient. Sequence analysis revealed that the patient was heterozygous for a point mutation (p.Arg337Cys) in the catalytic domain and polymorphisms: the decanucleotide insertion at the promoter re- gion, dimorphism (c.525C >T) in exon 5, and p.Arg413Gln in exon 8. Haplotype analysis clarified that p.Arg337Cys was located on the p.Arg413 allele (Ml allele). The other allele had the p.Arg413Gln polymor- phism(M2 allele) which is known to produce less FVII. Expression studies revealed that p.Arg337Cys causes impairment of FVII secretion. Insufficient secretion of FVII arising from both the p.Arg337Cys/M1 allele and the p.Arg337/M2 allele might lower the FVII level of this patient(<50%). The FVII level in a heterozygous FVII deficient patient might be influenced by F7 polymorphisms on the normal allele. There- fore, genetic analyses are important for the diagnosis of heterozygous FVII deficiency.

  6. Histone deacetylase inhibitor treatment attenuates coagulation imbalance in a lethal murine model of sepsis

    DEFF Research Database (Denmark)

    Zhao, Ting; Li, Yongqing; Liu, Baoling

    2014-01-01

    BACKGROUND: Sepsis has a profound impact on the inflammatory and hemostatic systems. In addition to systemic inflammation, it can produce disseminated intravascular coagulation, microvascular thrombosis, consumptive coagulopathy, and multiple organ failure. We have shown that treatment with suber...

  7. Decreased plasma levels of factor II + VII + X correlate with increased levels of soluble cytokine receptors in patients with malaria and meningococcal infections

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Hansen, M B; Rønn, A M

    1997-01-01

    The levels of coagulation factors II + VII + X and of blood platelets (thrombocytes) as well as of cytokines and soluble cytokine receptors were studied in the patients with malaria or meningococcal infections. The coagulation factors were decreased particularly in the meningococcal patients, while...... thrombocytes were lowest in the Plasmodium falciparum malaria patients. There was no correlation between factors II + VII + X and thrombocytes, but plasma levels of coagulation factors II + VII + X were found to correlate inversely with levels of soluble interleukin-2 receptor (sIL-2R) and soluble tumour...... necrosis factor-I (sTNF-RI) in patients with malaria and meningococcal infections. Elevated sIL-2R and sTNF-RI levels and decreased coagulation factors reverted to normal within 3-5 days after initiation of therapy in P. falciparum patients followed consecutively. Estimation of coagulation factors may...

  8. Tissue Factor–Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes

    OpenAIRE

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are...

  9. Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

    Science.gov (United States)

    Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

    2017-06-01

    During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation

  10. The Role of Factor XIa (FXIa) Catalytic Domain Exosite Residues in Substrate Catalysis and Inhibition by the Kunitz Protease Inhibitor Domain of Protease Nexin 2*

    Science.gov (United States)

    Su, Ya-Chi; Miller, Tara N.; Navaneetham, Duraiswamy; Schoonmaker, Robert T.; Sinha, Dipali; Walsh, Peter N.

    2011-01-01

    To select residues in coagulation factor XIa (FXIa) potentially important for substrate and inhibitor interactions, we examined the crystal structure of the complex between the catalytic domain of FXIa and the Kunitz protease inhibitor (KPI) domain of a physiologically relevant FXIa inhibitor, protease nexin 2 (PN2). Six FXIa catalytic domain residues (Glu98, Tyr143, Ile151, Arg3704, Lys192, and Tyr5901) were subjected to mutational analysis to investigate the molecular interactions between FXIa and the small synthetic substrate (S-2366), the macromolecular substrate (factor IX (FIX)) and inhibitor PN2KPI. Analysis of all six Ala mutants demonstrated normal Km values for S-2366 hydrolysis, indicating normal substrate binding compared with plasma FXIa; however, all except E98A and K192A had impaired values of kcat for S-2366 hydrolysis. All six Ala mutants displayed deficient kcat values for FIX hydrolysis, and all were inhibited by PN2KPI with normal values of Ki except for K192A, and Y5901A, which displayed increased values of Ki. The integrity of the S1 binding site residue, Asp189, utilizing p-aminobenzamidine, was intact for all FXIa mutants. Thus, whereas all six residues are essential for catalysis of the macromolecular substrate (FIX), only four (Tyr143, Ile151, Arg3704, and Tyr5901) are important for S-2366 hydrolysis; Glu98 and Lys192 are essential for FIX but not S-2366 hydrolysis; and Lys192 and Tyr5901 are required for both inhibitor and macromolecular substrate interactions. PMID:21778227

  11. Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders.

    Science.gov (United States)

    Ordookhani, Arash; Burman, Kenneth D

    2017-04-01

    There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted.

  12. Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

    Directory of Open Access Journals (Sweden)

    Gozzo A.J.

    2003-01-01

    Full Text Available Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis. The proteolytic enzymes involved in these processes are usually controlled by specific inhibitors and may be influenced by several factors including glycosaminoglycans, as recently demonstrated by our group. The aim of the present study was to investigate the effect of glycosaminoglycans (30 to 250 µg/ml on kallikrein activity on plasminogen and factor XII and on the inhibition of kallikrein by the plasma proteins C1-inhibitor and antithrombin. Almost all available glycosaminoglycans (heparin, heparan sulfate, bovine and tuna dermatan sulfate, chondroitin 4- and 6-sulfates reduced (1.2 to 3.0 times the catalytic efficiency of kallikrein (in a nanomolar range on the hydrolysis of plasminogen (0.3 to 1.8 µM and increased (1.9 to 7.7 times the enzyme efficiency in factor XII (0.1 to 10 µM activation. On the other hand, heparin, heparan sulfate, and bovine and tuna dermatan sulfate improved (1.2 to 3.4 times kallikrein inhibition by antithrombin (1.4 µM, while chondroitin 4- and 6-sulfates reduced it (1.3 times. Heparin and heparan sulfate increased (1.4 times the enzyme inhibition by the C1-inhibitor (150 nM.

  13. Effect of Centrifuge Temperature on Routine Coagulation Tests.

    Science.gov (United States)

    Yazar, Hayrullah; Özdemir, Fatma; Köse, Elif

    2018-01-01

    This study investigated the effects of cooled and standard centrifuges on the results of coagulation tests to examine the effects of centrifugation temperature. Equal-volume blood samples from each patient were collected at the same time intervals and subjected to standard (25°C) and cooled centrifugation (2-4°C). Subsequently, the prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, and D-dimer values were determined in runs with the same lot numbers in the same coagulation device using the Dia-PT R (PT and INR), Dia-PTT-liquid (aPTT), Dia-FIB (fibrinogen), and Dia-D-dimer kits, respectively. The study enrolled 771 participants. The PT was significantly (p centrifuges were as follows: PT 10.30 versus 10.50 s; PT (INR) 1.04 versus 1.09 s; APTT 28.90 versus 29.40 s; fibrinogen 321.5 versus 322.1 mg/dL; and D-dimer 179.5 versus 168.7 µg FEU/mL. There were significant differences (p centrifuges. Centrifuge temperature can have a significant effect on the results of coagulation tests. However, broad and specific disease-based studies are needed. © 2018 S. Karger AG, Basel.

  14. Thromboelastometry versus standard coagulation tests versus restrictive protocol to guide blood transfusion prior to central venous catheterization in cirrhosis: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Neto, Ary Serpa; do Prado, Rogerio Ruscitto; Silva, Eliezer; de Almeida, Marcio Dias; Correa, Thiago Domingos

    2017-02-27

    Liver failure patients have traditionally been empirically transfused prior to invasive procedures. Blood transfusion is associated with immunologic and nonimmunologic reactions, increased risk of adverse outcomes and high costs. Scientific evidence supporting empirical transfusion is lacking, and the best approach for blood transfusion prior to invasive procedures in cirrhotic patients has not been established so far. The aim of this study is to compare three transfusion strategies (routine coagulation test-guided - ordinary or restrictive, or thromboelastometry-guided) prior to central venous catheterization in critically ill patients with cirrhosis. Design and setting: a double-blinded, parallel-group, single-center, randomized controlled clinical trial in a tertiary private hospital in São Paulo, Brazil. adults (aged 18 years or older) admitted to the intensive care unit with cirrhosis and an indication for central venous line insertion. Patients will be randomly assigned to three groups for blood transfusion strategy prior to central venous catheterization: standard coagulation tests-based, thromboelastometry-based, or restrictive. The primary efficacy endpoint will be the proportion of patients transfused with any blood product prior to central venous catheterization. The primary safety endpoint will be the incidence of major bleeding. Secondary endpoints will be the proportion of transfusion of fresh frozen plasma, platelets and cryoprecipitate; infused volume of blood products; hemoglobin and hematocrit before and after the procedure; intensive care unit and hospital length of stay; 28-day and hospital mortality; incidence of minor bleeding; transfusion-related adverse reactions; and cost analysis. This study will evaluate three strategies to guide blood transfusion prior to central venous line placement in severely ill patients with cirrhosis. We hypothesized that thromboelastometry-based and/or restrictive protocols are safe and would significantly

  15. C-terminal peptides of tissue factor pathway inhibitor are novel host defense molecules.

    Science.gov (United States)

    Papareddy, Praveen; Kalle, Martina; Kasetty, Gopinath; Mörgelin, Matthias; Rydengård, Victoria; Albiger, Barbara; Lundqvist, Katarina; Malmsten, Martin; Schmidtchen, Artur

    2010-09-03

    Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation, but may, via its C terminus, also modulate cell surface, heparin, and lipopolysaccharide interactions as well as participate in growth inhibition. Here we show that C-terminal TFPI peptide sequences are antimicrobial against the gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungi Candida albicans and Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen for the "classic" human antimicrobial peptide LL-37. The killing of E. coli, but not P. aeruginosa, by the C-terminal peptide GGLIKTKRKRKKQRVKIAYEEIFVKNM (GGL27), was enhanced in human plasma and largely abolished in heat-inactivated plasma, a phenomenon linked to generation of antimicrobial C3a and activation of the classic pathway of complement activation. Furthermore, GGL27 displayed anti-endotoxic effects in vitro and in vivo in a mouse model of LPS shock. Importantly, TFPI was found to be expressed in the basal layers of normal epidermis, and was markedly up-regulated in acute skin wounds as well as wound edges of chronic leg ulcers. Furthermore, C-terminal fragments of TFPI were associated with bacteria present in human chronic leg ulcers. These findings suggest a new role for TFPI in cutaneous defense against infections.

  16. Distribution functions and moments in the theory of coagulation

    International Nuclear Information System (INIS)

    Pich, J.

    1990-04-01

    Different distribution functions and their moments used in the Theory of coagulation are summarized and analysed. Relations between the moments of these distribution functions are derived and the physical meaning of individual moments is briefly discussed. The time evolution of the moment of order zero (total number concentration) during the coagulation process is analysed for the general kernel of the Smoluchowski equation. On this basis the time evolution of certain physically important quantities related to this moment such as mean particle size, surface and volume as well as surface concentration is described. Equations for the half time of coagulation for the general collision frequency factor are derived. (orig.) [de

  17. Retinal venous thrombosis in a young patient with coagulation factor XII deficiency.

    Science.gov (United States)

    Borrego-Sanz, L; Santos-Bueso, E; Sáenz-Francés, F; Martínez-de-la-Casa, J M; García-Feijoo, J; Gegúndez-Fernández, J A; García-Sánchez, J

    2014-08-01

    A 35-year-old woman, with no relevant medical history, was referred for sudden vision loss in the left eye. Ophthalmological examination showed best corrected visual acuity of 1.0 in the right eye and 0.3 in left eye, with normal anterior pole and intraocular pressure. Fundus examination of the left eye revealed a venous thrombosis in the superior temporal branch, with dilated and tortuous retinal veins. The patient was referred to the hematology unit for thrombophilia study, and was diagnosed with a coagulation XII or Hageman factor deficiency. The development of retinal vessel occlusions, in patients under 50 years of age, is frequently associated with thrombophilia or hypercoagulability disorders. Factor XII deficiency is a rare condition, and its presence could contribute to a higher risk of thromboembolic events. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  18. Assessment of the frequency of regulatory T cells (CD4+CD25+CD127-) in children with hemophilia A: relation to factor VIII inhibitors and disease severity.

    Science.gov (United States)

    El-Asrar, Mohamed Abo; Hamed, Ahmed El-Saeed; Darwish, Yasser Wagih; Ismail, Eman Abdel Rahman; Ismail, Noha Ali

    2016-01-01

    A rapidly growing evidence showed that regulatory T cells (Tregs) play a crucial role in tolerance to coagulation factors and may be involved in the pathogenesis of inhibitor formation in patients with hemophilia. We determined the percentage of Tregs (CD4CD25CD127) in 45 children with hemophilia A compared with 45 healthy controls, and assessed their relation to the clinical characteristics of patients and factor VIII (FVIII) inhibitors. Patients were studied stressing on frequency of bleeding attacks, joint pain, history of viral hepatitis, and the received therapy (FVIII precipitate/cryotherapy). FVIII activity and FVIII inhibitors were assessed with flow cytometric analysis of CD4CD25CD127 Tregs. According to residual FVIII activity levels, 30 patients (66.7%) had mild/moderate hemophilia A, whereas 15 (33.3%) patients had severe hemophilia A. The frequency of Tregs was significantly lower among all patients with hemophilia A compared with controls (2.59 ± 1.1 versus 3.73 ± 1.12%; P = 0.002). Tregs were significantly decreased among patients with FVIII inhibitors compared with the inhibitor-negative group (P hemophilia A had lower Tregs levels than those without (P = 0.34 and P = 0.011, respectively). A significant positive correlation was found between the percentage of Tregs and FVIII among hemophilia A patients. ROC curve analysis revealed that the cut-off value of Tregs at 1.91% could differentiate patients with and without FVIII inhibitors, with a sensitivity of 100% and a specificity of 91.3%. We suggest that alteration in the frequency of Tregs in young patients with hemophilia A may contribute to inhibitor formation and disease severity.

  19. Evaluation of Disseminated Intravascular Coagulation in the Craniocerebral Traumas

    Directory of Open Access Journals (Sweden)

    Faruk Altinel

    2014-06-01

    Full Text Available Traumatic injury is one of the most important cause of disseminated intravascular coagulation (DIC. It occurs because of blood loss and hemodilution due to fluid resuscitation. The incidence of trauma associated DIC is mainly higher in the craniocerebral traumas. Even though craniocerebral trauma related DIC is well defined, the pathophysiology has been poorly characterized in the literature. Due to the fact that brain tissue is highly significant for procoagulant molecules, craniocerebral traumas are closely related to DIC. In the current study, 30 patients admitted to emergency room have been considered on the first and fifth day of admission to the hospital for the coagulation tests to evaluate DIC in both two groups. [Cukurova Med J 2014; 39(3.000: 488-495

  20. Predictive Factors for Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Shusuke Yagi

    2015-08-01

    Full Text Available BackgroundPredictive factors for the efficacy of dipeptidyl peptidase-4 (DPP-4 inhibitors for lowering glycosylated hemoglobin (HbA1c remain unclear in patients with type 2 diabetes mellitus. The aim of this study is therefore to clarify predictive factors of the efficacy of DPP-4 inhibitors for lowering HbA1c after 12 months of treatment.MethodsA total of 191 consecutive type 2 diabetic patients (male sex 55%, mean age, 68.3±35.8 years, who had been treated with DPP-4 inhibitors for 12 months, were enrolled in this study and evaluated retrospectively.ResultsAfter 12 months of DPP-4 inhibitor treatment, random blood glucose level, and HbA1c level, decreased from 167±63 to 151±49 mg/dL (P<0.01, and from 7.5%±1.3% to 6.9%±0.9% (P<0.01 respectively, without severe side effects. Multiple regression analysis showed that predictors of DPP-4 inhibitor treatment efficacy in lowering HbA1c level after 12 months were a decrease in HbA1c level after 3 months of treatment, a high baseline HbA1c level, a low baseline body mass index, and the absence of coronary artery disease.ConclusionMost suitable candidates for treatment with DPP-4 inhibitors are diabetics who are not obese and do not have coronary artery disease. In addition, long-term efficacy of DPP-4 inhibitors can be predicted by decrement of HbA1c after 3 months of treatment.

  1. The donor line break cannula: effect on the donation process, blood component quality and transfusion microbiology testing of an important new blood bag safety feature.

    Science.gov (United States)

    Nightingale, M J; Beard, M J; Bennett, J; Hambleton, R; Ramskill, S; Thomas, S

    2013-08-01

    The use of blood packs with an integral sampling system can result in anti-coagulant from the main bag reaching the sample pouch via the donor line, causing delayed coagulation of blood samples. In NHS Blood and Transplant, this has prevented the use of serum, the preferred matrix for transfusion microbiology (TM) testing, which has led to an increased false positive rate with ethylenediaminetetraacetic acid (EDTA) plasma. There is also a remote possibility of false negative results owing to sample dilution. Manufacturers have responded by offering packs with a donor line break cannula (DLBC) to prevent these adverse effects. The aims of this study were to assess the impact of DLBC packs on donation, blood component quality and of the potential return to serum for TM testing. DLBC packs from three manufacturers were assessed against control packs of the same dimensions and configuration. Donation duration, flow rate, platelet factor 4, prothrombin fragment 1+2, haemolysis and collection and processing incidents were compared. Results indicated no clinically significant adverse effect from the DLBC on the activation state of platelets, the coagulation cascade or increased haemolysis. Donation duration and blood collection and processing incident rates for DLBC packs were not significantly different to controls. The use of DLBC packs would reduce the complexity of manipulations during blood collection and therefore the likelihood of microbially contaminated donations (incorrect skin core diversion) and false negative TM tests. DLBC packs would enable the use of serum for TM testing with a significant reduction in false positive tests compared to EDTA plasma. © 2013 The Authors. Transfusion Medicine © 2013 British Blood Transfusion Society.

  2. Surgery in adults with congenital coagulation deficiencies: how do we do it?

    Directory of Open Access Journals (Sweden)

    Dušan Andoljšek

    2012-12-01

    Conclusions: Surgery in adults with congenital coagulation disorders is always challenging. The risk of complications is average or lower if there is an adequate level of medical treatement and organisation. Treatment concentrates are safe, no inhibitor was found. Measures other thanmedicines are quite effective for prophylaxis of thrombosis. Surgery is partly specific for this population (hemophilic polyarthropathy but it also reflects common problems of the aging population.

  3. SGLT2 Inhibitors and the Diabetic Kidney.

    Science.gov (United States)

    Fioretto, Paola; Zambon, Alberto; Rossato, Marco; Busetto, Luca; Vettor, Roberto

    2016-08-01

    Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether

  4. Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography

    OpenAIRE

    Mousavi Hosseini, Kamran; Nasiri, Saleh

    2015-01-01

    Background: Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII conce...

  5. Coagulation profiles of healthy Andalusian donkeys are different than those of healthy horses.

    Science.gov (United States)

    Mendoza, F J; Perez-Ecija, R A; Monreal, L; Estepa, J C

    2011-01-01

    Coagulation disorders are frequently diagnosed, especially in hospitalized equidae, and result in increased morbidity and mortality. However, hemostatic reference intervals have not been established for donkeys yet. To determine whether the most common coagulation parameters used in equine practice are different between healthy donkeys and horses. Thirty-eight healthy donkeys and 29 healthy horses. Blood samples were collected to assess both coagulation and fibrinolytic systems by determination of platelet count, fibrinogen concentration, clotting times (prothrombin time [PT] and activated partial thromboplastin time [aPTT]), fibrin degradation products (FDP) and D-Dimer concentrations. PT and aPTT in donkeys were significantly (P donkeys than in horses. The coagulation parameters most commonly determined in equine practice are different in donkeys compared with horses. Thus, the use of normal reference ranges reported previously for healthy horses in donkeys might lead to a misdiagnosis of coagulopathy in healthy donkeys, and unnecessary treatments in sick donkeys. This is the first report of normal coagulation profile results in donkeys, and further studies are warranted to elucidate the physiological mechanisms of the differences observed between donkeys and horses. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  6. In vitro investigation of the effects of exogenous sugammadex on coagulation in orthopedic surgical patients.

    Science.gov (United States)

    Lee, Il Ok; Kim, Young Sung; Chang, Hae Wone; Kim, Heezoo; Lim, Byung Gun; Lee, Mido

    2018-05-24

    Previous studies have shown that sugammadex resulted in the prolongation of prothrombin time and activated partial thromboplastin time. In this study, we aimed to investigate the in vitro effects of exogenous sugammadex on the coagulation variables of whole blood in healthy patients who underwent orthopedic surgery. The effects of sugammadex on coagulations were assessed using thromboelastography (TEG) in kaolin-activated citrated blood samples taken from 14 healthy patients who underwent orthopedic surgery. The in vitro effects of three different concentrations of sugammadex (42, 193, and 301 μg mL - 1 ) on the TEG profiles were compared with those of the control (0 μg mL - 1 ). Previous studies indicated that these exogenous concentrations correspond to the approximate maximum plasma concentrations achieved after the administration of 4, 16, and 32 mg kg - 1 sugammadex to healthy subjects. Increased sugammadex concentrations were significantly associated with reduced coagulation, as evidenced by increases in reaction time (r), coagulation time, and time to maximum rate of thrombus generation (TMRTG), and decreases in the angle, maximum amplitude, and maximum rate of thrombus generation. Compared with the control, the median percentage change (interquartile range) in the TEG values of the samples treated with the highest exogenous sugammadex concentration was the greatest for r, 53% (26, 67.3%), and TMRTG, 48% (26, 59%). This in vitro study suggests that supratherapeutic doses of exogenous sugammadex might be associated with moderate hypocoagulation in the whole blood of healthy subjects. identifier:  UMIN000029081 , registered 11 September 2017.

  7. Molecular cloning of Kazal-type proteinase inhibitor of the shrimp Fenneropenaeus chinensis.

    Science.gov (United States)

    Kong, Hee Jeong; Cho, Hyun Kook; Park, Eun-Mi; Hong, Gyeong-Eun; Kim, Young-Ok; Nam, Bo-Hye; Kim, Woo-Jin; Lee, Sang-Jun; Han, Hyon Sob; Jang, In-Kwon; Lee, Chang Hoon; Cheong, Jaehun; Choi, Tae-Jin

    2009-01-01

    Proteinase inhibitors play important roles in host defence systems involving blood coagulation and pathogen digestion. We isolated and characterized a cDNA clone for a Kazal-type proteinase inhibitor (KPI) from a hemocyte cDNA library of the oriental white shrimp Fenneropenaeus chinensis. The KPI gene consists of three exons and two introns. KPI cDNA contains an open reading frame of 396 bp, a polyadenylation signal sequence AATAAA, and a poly (A) tail. KPI cDNA encodes a polypeptide of 131 amino acids with a putative signal peptide of 21 amino acids. The deduced amino acid sequence of KPI contains two homologous Kazal domains, each with six conserved cysteine residues. The mRNA of KPI is expressed in the hemocytes of healthy shrimp, and the higher expression of KPI transcript is observed in shrimp infected with the white spot syndrome virus (WSSV), suggesting a potential role for KPI in host defence mechanisms.

  8. TRAITEMENT DES EAUX USEES PAR COAGULATION-FLOCULATION EN UTILISANT LE SULFATE D’ALUMINIUM COMME COAGULANT

    OpenAIRE

    Nora SEGHAIRI; Leila MIMECHE; Adel BOUZID; Yassir AYACHI

    2017-01-01

    Domestic wastewater treatment by coagulation-flocculation is widely used internationally. This treatment reduces color and turbidity, indicating organic and inorganic contaminants, but at acceptable levels for treated waste water discharged into the receiving environment. The objective of this study is to optimize the treatment of wastewater by coagulation-flocculation using aluminum sulphate as a coagulant. Various reaction parameters are taken into account, such as the coagulant dose,...

  9. The preliminary observation of the changes of β-actin,coagulant and inflammatory factors in mice serum induced by γ rays irradiation

    International Nuclear Information System (INIS)

    Zhang Qingzhi; Wang Jia; Cheng Ying; Li Mingjuan; Min Rui

    2010-01-01

    In order to learn the effect of β-actin in acute radiation injury, the changeable pattern with time of plasma β-actin, PT, APTT, FIB and IL-8 in mice spleen tissue exposed to 6 Gy γ-rays radiation was investigated.Blood and spleen were collected at immediate, 1, 2, 3, 4, 7 and 14 d after irradiation, respectively. The contents of blood β-actin were detected by magnetic bead separation enzyme-linked immunosorbent. An STAGO blood coagulation instrument was used to determine PT, APTT and FIB. DNA expression of IL-8 was detected by real time-PCR analyzer. The results show that the level of β-actin in serum of irradiated mice is higher than that of normal control group at all different post-irradiation time points although the change of β-actin in serum of irradiated mice with time schedule shows a pattern which increases within 1d and declines beyond 1d. The trend of the changes in plasma PT, APTT, FIB and in spleen IL-8 and time pattern of these changes are similar to that in plasma β-actin in irradiated mice. The difference in values and the time phase between plasma β-actin and other indexes is the reaching time of peak values and the declining levels of the values. These results are valuable for studying the role of β-actin in acute radiation sickness pathology process and can be used to explore new factors influencing and regulating pathology process. (authors)

  10. The origins of enhanced activity in factor VIIa analogs and the interplay between key allosteric sites revealed by hydrogen exchange mass spectrometry

    DEFF Research Database (Denmark)

    Rand, Kasper D; Andersen, Mette D; Olsen, Ole H

    2008-01-01

    Factor VIIa (FVIIa) circulates in the blood in a zymogen-like state. Only upon association with membrane-bound tissue factor (TF) at the site of vascular injury does FVIIa become active and able to initiate blood coagulation. Here we used hydrogen exchange monitored by mass spectrometry to invest......Factor VIIa (FVIIa) circulates in the blood in a zymogen-like state. Only upon association with membrane-bound tissue factor (TF) at the site of vascular injury does FVIIa become active and able to initiate blood coagulation. Here we used hydrogen exchange monitored by mass spectrometry...... to investigate the conformational effects of site-directed mutagenesis at key positions in FVIIa and the origins of enhanced intrinsic activity of FVIIa analogs. The differences in hydrogen exchange of two highly active variants, FVIIa(DVQ) and FVIIa(VEAY), imply that enhanced catalytic efficiency was attained...

  11. Defibrotide interferes with several steps of the coagulation-inflammation cycle and exhibits therapeutic potential to treat severe malaria.

    Science.gov (United States)

    Francischetti, Ivo M B; Oliveira, Carlo J; Ostera, Graciela R; Yager, Stephanie B; Debierre-Grockiego, Françoise; Carregaro, Vanessa; Jaramillo-Gutierrez, Giovanna; Hume, Jen C C; Jiang, Lubin; Moretz, Samuel E; Lin, Christina K; Ribeiro, José M C; Long, Carole A; Vickers, Brandi K; Schwarz, Ralph T; Seydel, Karl B; Iacobelli, Massimo; Ackerman, Hans C; Srinivasan, Prakash; Gomes, Regis B; Wang, Xunde; Monteiro, Robson Q; Kotsyfakis, Michail; Sá-Nunes, Anderson; Waisberg, Michael

    2012-03-01

    The coagulation-inflammation cycle has been implicated as a critical component in malaria pathogenesis. Defibrotide (DF), a mixture of DNA aptamers, displays anticoagulant, anti-inflammatory, and endothelial cell (EC)-protective activities and has been successfully used to treat comatose children with veno-occlusive disease. DF was investigated here as a drug to treat cerebral malaria. DF blocks tissue factor expression by ECs incubated with parasitized red blood cells and attenuates prothrombinase activity, platelet aggregation, and complement activation. In contrast, it does not affect nitric oxide bioavailability. We also demonstrated that Plasmodium falciparum glycosylphosphatidylinositol (Pf-GPI) induces tissue factor expression in ECs and cytokine production by dendritic cells. Notably, dendritic cells, known to modulate coagulation and inflammation systemically, were identified as a novel target for DF. Accordingly, DF inhibits Toll-like receptor ligand-dependent dendritic cells activation by a mechanism that is blocked by adenosine receptor antagonist (8-p-sulfophenyltheophylline) but not reproduced by synthetic poly-A, -C, -T, and -G. These results imply that aptameric sequences and adenosine receptor mediate dendritic cells responses to the drug. DF also prevents rosetting formation, red blood cells invasion by P. falciparum and abolishes oocysts development in Anopheles gambiae. In a murine model of cerebral malaria, DF affected parasitemia, decreased IFN-γ levels, and ameliorated clinical score (day 5) with a trend for increased survival. Therapeutic use of DF in malaria is proposed.

  12. Identification of coagulation gene 3′UTR variants that are potentially regulated by microRNAs

    NARCIS (Netherlands)

    Vossen, Carla Y.; van Hylckama Vlieg, Astrid; Teruel-Montoya, Raúl; Salloum-Asfar, Salam; de Haan, Hugoline G.; Corral, Javier; Reitsma, Pieter H.; Koeleman, Bobby P.C.; Martínez, Constantino

    2017-01-01

    MicroRNAs have been recognized as critical regulators of gene expression and might affect the risk of venous thrombosis. We aimed to identify 3′ untranslated region (UTR) variants in coagulation genes that influence coagulation factor levels and venous thrombosis risk. The 3′UTR of coagulation genes

  13. Non anti-coagulant factors associated with filter life in continuous renal replacement therapy (CRRT): a systematic review and meta-analysis.

    Science.gov (United States)

    Brain, Matthew; Winson, Elizabeth; Roodenburg, Owen; McNeil, John

    2017-02-20

    Optimising filter life and performance efficiency in continuous renal replacement therapy has been a focus of considerable recent research. Larger high quality studies have predominantly focussed on optimal anticoagulation however CRRT is complex and filter life is also affected by vascular access, circuit and management factors. We performed a systematic search of the literature to identify and quantify the effect of vascular access, circuit and patient factors that affect filter life and presented the results as a meta-analysis. A systematic review and meta-analysis was performed by searching Pubmed (MEDLINE) and Ovid EMBASE libraries from inception to 29 th February 2016 for all studies with a comparator or independent variable relating to CRRT circuits and reporting filter life. Included studies documented filter life in hours with a comparator other than anti-coagulation intervention. All studies comparing anticoagulation interventions were searched for regression or hazard models pertaining to other sources of variation in filter life. Eight hundred nineteen abstracts were identified of which 364 were selected for full text analysis. 24 presented data on patient modifiers of circuit life, 14 on vascular access modifiers and 34 on circuit related factors. Risk of bias was high and findings are hypothesis generating. Ranking of vascular access site by filter longevity favours: tunnelled semi-permanent catheters, femoral, internal jugular and subclavian last. There is inconsistency in the difference reported between femoral and jugular catheters. Amongst published literature, modality of CRRT consistently favoured continuous veno-venous haemodiafiltration (CVVHD-F) with an associated 44% lower failure rate compared to CVVH. There was a trend favouring higher blood flow rates. There is insufficient data to determine advantages of haemofilter membranes. Patient factors associated with a statistically significant worsening of filter life included mechanical

  14. Coagulation competence for predicting perioperative hemorrhage in patients treated with lactated Ringer's vs. Dextran

    DEFF Research Database (Denmark)

    Rasmussen, Kirsten C; Højskov, Michael; Johansson, Per Ingemar

    2015-01-01

    to receive either lactated Ringer's solution or Dextran 70 (Macrodex ®) that affects coagulation competence. RESULTS: By thrombelastography evaluated coagulation competence, Dextran 70 reduced "maximal amplitude" (MA) by 25 % versus a 1 % reduction with the administration of lactated Ringer's solution (P ....001). Blinded evaluation of the blood loss was similar in the two groups of patients - 2339 ml with the use of Dextran 70 and 1822 ml in the lactated Ringer's group (P = 0.27). Yet, the blood loss was related to the reduction in MA (r = -0.427, P = 0.008) and by multiple regression analysis independently...... associated with MA (P = 0.01). Thus, 11 patients in the dextran group (58 %) developed a clinical significant blood loss (>1500 ml) compared to only four patients (22 %) in the lactated Ringer's group (P = 0.04). CONCLUSIONS: With the use of Dextran 70 vs. lactated Ringer's solution during cystectomy...

  15. Coagulation performance of a novel poly-ferric-acetate (PFC) coagulant in phosphate-kaolin synthetic water treatment

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Yanxin; Lu, Jinpeng; Dong, Xiongzi; Yao, Chengli [Hefei Normal University, Hefei (China); Hao, Jianwen [Anhui Vocational and Technical College, Hefei (China)

    2017-10-15

    The process of coagulation-flocculation is increasingly applied in wastewater treatment. And the polymerized inorganic coagulants are widely used among these coagulation-flocculation processes. However, conventional coagulants using sulfates or chlorides as counter anion may give rise to corrosion. The purpose of this study was to synthesize PFC coagulants in which acetate is used as counter anion. The influences on the preparation of PFC were optimized. The synthesis was done at the optimum conditions, such as temperature of 60 .deg. C, the Fe/CH{sub 3}COOH molar ratio of 1 : 4.0 and reaction time of 6 h, respectively. The prepared PFC coagulants were characterized by Fourier transform infrared (FTIR) spectrophotometry and scanning electron microscopy (SEM). PFC was found to mainly form complexation polymeric species and present more cluster and lamellar structure. A series of jar tests were carried out to study the coagulation performance of PFC and PFS in phosphate-kaolin synthetic water treatment. Results showed that the coagulation performance of PFC was more efficient than PFS's in terms of the phosphorus removal efficiency and the residual turbidity. Due to using acetate as counter anion to iron, PFC is less harmful to the processes of water treatment and equipment than that of the conventional coagulants applied chlorides or sulfates. Therefore, PFC is a promising coagulant in the process of corrosion sensitive applications and the process of wastewater containing phosphorus treatment.

  16. Coagulation factor VII is regulated by androgen receptor in breast cancer.

    Science.gov (United States)

    Naderi, Ali

    2015-02-01

    Androgen receptor (AR) is widely expressed in breast cancer; however, there is limited information on the key molecular functions and gene targets of AR in this disease. In this study, gene expression data from a cohort of 52 breast cancer cell lines was analyzed to identify a network of AR co-expressed genes. A total of 300 genes, which were significantly enriched for cell cycle and metabolic functions, showed absolute correlation coefficients (|CC|) of more than 0.5 with AR expression across the dataset. In this network, a subset of 35 "AR-signature" genes were highly co-expressed with AR (|CC|>0.6) that included transcriptional regulators PATZ1, NFATC4, and SPDEF. Furthermore, gene encoding coagulation factor VII (F7) demonstrated the closest expression pattern with AR (CC=0.716) in the dataset and factor VII protein expression was significantly associated to that of AR in a cohort of 209 breast tumors. Moreover, functional studies demonstrated that AR activation results in the induction of factor VII expression at both transcript and protein levels and AR directly binds to a proximal region of F7 promoter in breast cancer cells. Importantly, AR activation in breast cancer cells induced endogenous factor VII activity to convert factor X to Xa in conjunction with tissue factor. In summary, F7 is a novel AR target gene and AR activation regulates the ectopic expression and activity of factor VII in breast cancer cells. These findings have functional implications in the pathobiology of thromboembolic events and regulation of factor VII/tissue factor signaling in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Slaughterhouse wastewater treatment by combined chemical coagulation and electrocoagulation process.

    Science.gov (United States)

    Bazrafshan, Edris; Kord Mostafapour, Ferdos; Farzadkia, Mehdi; Ownagh, Kamal Aldin; Mahvi, Amir Hossein

    2012-01-01

    Slaughterhouse wastewater contains various and high amounts of organic matter (e.g., proteins, blood, fat and lard). In order to produce an effluent suitable for stream discharge, chemical coagulation and electrocoagulation techniques have been particularly explored at the laboratory pilot scale for organic compounds removal from slaughterhouse effluent. The purpose of this work was to investigate the feasibility of treating cattle-slaughterhouse wastewater by combined chemical coagulation and electrocoagulation process to achieve the required standards. The influence of the operating variables such as coagulant dose, electrical potential and reaction time on the removal efficiencies of major pollutants was determined. The rate of removal of pollutants linearly increased with increasing doses of PACl and applied voltage. COD and BOD(5) removal of more than 99% was obtained by adding 100 mg/L PACl and applied voltage 40 V. The experiments demonstrated the effectiveness of chemical and electrochemical techniques for the treatment of slaughterhouse wastewaters. Consequently, combined processes are inferred to be superior to electrocoagulation alone for the removal of both organic and inorganic compounds from cattle-slaughterhouse wastewater.

  18. Slaughterhouse Wastewater Treatment by Combined Chemical Coagulation and Electrocoagulation Process

    Science.gov (United States)

    Bazrafshan, Edris; Kord Mostafapour, Ferdos; Farzadkia, Mehdi; Ownagh, Kamal Aldin; Mahvi, Amir Hossein

    2012-01-01

    Slaughterhouse wastewater contains various and high amounts of organic matter (e.g., proteins, blood, fat and lard). In order to produce an effluent suitable for stream discharge, chemical coagulation and electrocoagulation techniques have been particularly explored at the laboratory pilot scale for organic compounds removal from slaughterhouse effluent. The purpose of this work was to investigate the feasibility of treating cattle-slaughterhouse wastewater by combined chemical coagulation and electrocoagulation process to achieve the required standards. The influence of the operating variables such as coagulant dose, electrical potential and reaction time on the removal efficiencies of major pollutants was determined. The rate of removal of pollutants linearly increased with increasing doses of PACl and applied voltage. COD and BOD5 removal of more than 99% was obtained by adding 100 mg/L PACl and applied voltage 40 V. The experiments demonstrated the effectiveness of chemical and electrochemical techniques for the treatment of slaughterhouse wastewaters. Consequently, combined processes are inferred to be superior to electrocoagulation alone for the removal of both organic and inorganic compounds from cattle-slaughterhouse wastewater. PMID:22768233

  19. Inhibitors of serotonin reuptake and specific imipramine binding in human blood plasma

    International Nuclear Information System (INIS)

    Brusov, O.S.; Fomenko, A.M.; Katasonov, A.B.; Lidemann, R.R.

    1985-01-01

    This paper describes a method of extraction of endogenous inhibitors of specific IMI binding and of 5-HT reuptake, from human blood plasma and the heterogeneity of these compounds is demonstrated. Specific binding was determined as the difference between binding of 3 H-IMI in the absence and in the presence of 50 microM IMI. Under these conditions, specific binding amounted to 70-80% of total binding of 3 H-IMI. It is shown that extract obtained from human blood contains a material which inhibits dose-dependently both 5-HT reuptake and specific binding of 3 H-IMI. Gel-chromatography of extracts of human blood plasma on Biogel P-2 is also shown

  20. [The activity of formaldehyde, glutardialdehyde, peracetic acid, chloramine T (N-chlor-4-toluolsulfonamide), m-cresol, ethanol and benzyldimethyldodecylammonium bromide against bacteria which are found in coagulated blood. (Model studies for chemical disinfection of instruments].

    Science.gov (United States)

    Spicher, G; Peters, J

    1991-05-01

    The experiments were performed using frosted glass as carrier with its surface being contaminated with whole blood containing Staphylococcus aureus as test organism. At the time of sampling, a heparin preparation was added to the blood to prevent premature coagulation. After addition of the staphylococci, coagulation was initiated by means of a heparin antagonist. 10, 25, 50, 100, and 150 microliters, respectively, of the blood were homogeneously spread on rectangular test areas of 10 x 20 mm. After the blood had coagulated, each of the test objects was placed in 15 ml of the solution (20 degrees C) containing the active ingredient tested for 60 min. After that, the test objects were removed from the disinfectant and, in order to inactivate any adhering active components, treated with a neutralizing solution of suitable composition. The number of viable germs (colony-forming units) was determined quantitatively. The blood samples were ground together with quartz sand. Aliquots of the diluted suspensions were mixed with molten agar medium. The plates then were incubated at 37 degrees C over a period of 14 days. The relative number of viable germs (N/No) per test object was calculated from the number of colonies. Plotting of the microbicidal effects obtained (log N/No] versus the concentration of the active substance (see Figs. 1-3) yielded curves differing in some characteristics as e.g. curvature, slope of the lower curve section (log N/No). less than -3), concentration range according to the layer thickness of the contamination. To visualize the reduction of the efficacy of the respective disinfectants caused by blood, the concentrations of active components were determined which are necessary to achieve a microbicidal effect of log (N/No) = -4. These concentrations were plotted versus the amounts of blood per test area (Fig. 4). The resulting curve for formaldehyde was slightly U-shaped. With a raising amount of blood, the concentration required slightly

  1. Are olive oil diets antithrombotic?

    DEFF Research Database (Denmark)

    Larsen, L. F.; Jespersen, J.; Marckmann, Peter

    1999-01-01

    compared the effects of virgin olive oil with those of rapeseed and sunflower oils on blood coagulation factor VII (FVII), a key factor in thrombogenesis. DESIGN: In a randomized and strictly controlled crossover study, 18 healthy young men consumed diets enriched with 5 g/MJ (19% of total energy) olive...... FVII (FVIIa) were 11.3 +/- 5.1 U/L lower after olive oil than after sunflower oil, an 18% reduction (P diets...... with respect to nonfasting factor VII coagulant activity (FVII:c), prothrombin fragment 1+2 (F1+2), and tissue factor pathway inhibitor (TFPI) concentrations, or with respect to fasting plasma values of FVII protein, FVII:c, FVIIa, F1+2, or TFPI. CONCLUSION: A background diet rich in olive oil may attenuate...

  2. Gene Delivery of Activated Factor VII Using Alternative Adeno-Associated Virus Serotype Improves Hemostasis in Hemophiliac Mice with FVIII Inhibitors and Adeno-Associated Virus Neutralizing Antibodies.

    Science.gov (United States)

    Sun, Junjiang; Hua, Baolai; Chen, Xiaojing; Samulski, Richard J; Li, Chengwen

    2017-08-01

    While therapeutic expression of coagulation factors from adeno-associated virus (AAV) vectors has been successfully achieved in patients with hemophilia, neutralizing antibodies to the vector and inhibitory antibodies to the transgene severely limit efficacy. Indeed, approximately 40% of mice transduced with human factor VIII using the AAV8 serotype developed inhibitory antibodies to factor VIII (FVIII inhibitor), as well as extremely high titers (≥1:500) of neutralizing antibodies to AAV8. To correct hemophilia in these mice, AAV9, a serotype with low in vitro cross-reactivity (≤1:5) to anti-AAV8, was used to deliver mouse-activated factor VII (mFVIIa). It was found that within 6 weeks of systemic administration of 2 × 10 13 particles/kg of AAV9/mFVIIa, hemophiliac mice with FVIII inhibitors and neutralizing antibodies (NAb) to AAV8 achieved hemostasis comparable to that in wild-type mice, as measured by rotational thromboelastometry. A level of 737 ng/mL mFVIIa was achieved after AAV9/mFVIIa adminstration compared to around 150 ng/mL without vector treatment, and concomitantly prothrombin time was shortened. Tissues collected after intra-articular hemorrhage from FVIII-deficient mice and mice with FVIII inhibitors were scored 4.7 and 5.5, respectively, on a scale of 0-10, indicating significant pathological damage. However, transduction with AAV9/mFVIIa decreased pathology scores to 3.6 and eliminated hemosiderin iron deposition in the synovium in most mice. Collectively, these results suggest that application of alternative serotypes of AAV vector to deliver bypassing reagents has the potential to correct hemophilia and prevent hemoarthrosis, even in the presence of FVIII inhibitor and neutralizing antibodies to AAV.

  3. Analysis of the Factors Associated with Abnormal Coagulation and Prognosis
in Patients with Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yanhua LI

    2014-11-01

    Full Text Available Background and objective The activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are associated with high risk of invasion, metastases, and negative final outcomes. Non-small cell lung cancer (NSCLC accounts for approximately 80% to 85% of all lung malignancies. This study aims to investigate the prognostic value of blood coagulation tests for NSCLC and provide a reference to patients on the prevention and treatment of thrombophilia. Methods Data were collected from 604 cases of hospitalized patients with histologically confirmed NSCLC from January 2009 to December 2012 at the Fourth Hospital of Hebei Medical University. Data included the related indexes of coagulation function in patients before treatment [(i.e., prothrombin time (PT, prothrombin time activity (PTA, international normalized ratio (INR, activated partial thromboplastin time (APTT, fibrinogen (Fib, D-dimer, and platelet count], as well as sex, age, pathological type, TNM stage, and lymph node status. Fifty control subjects without cancer were included in the analysis. Statistical analysis was conducted by using SPSS 13.0 software. Results The plasma level of all coagulation tests including D-dimer, Fib, PT, APTT, INR, and platelet counts revealed statistically significant differences between the patient and control group (P<0.001 for all variables; P=0.001,5 and P=0.004,5 for Fib and platelet counts, respectively. The squamous subtype exhibited high plasma Fib levels (P<0.001 compared with adenocarcinoma cell lung cancer patients. Fib and PLT levels increased (P<0.001 and P=0.014, respectively, and aPTT decreased (P<0.001 in patients at stages III and IV compared with those in patients at stages I and II. aPTT decreased significantly (P<0.001, and Fib and D-dimer levels increased (P<0.001 and P=0.048, respectively in N1-3 patients with NSCLC compared with those of N0 patients. Prolonged PT and INR, high plasma Fib levels, and

  4. The investigation of coagulation activity of natural coagulants extracted from different strains of common bean

    Directory of Open Access Journals (Sweden)

    Šćiban Marina B.

    2010-01-01

    Full Text Available Coagulation and flocculation by adding chemicals are the methods that are usually used for removal of water turbidity. This study is concerned with the coagulation activity of extracts of various strains of bean. The aim was to ascertain if bean varieties influence coagulation activity. Active components were extracted from 1 g of ground sample with 100 ml distilled water. Contents of dry matter and nitrogen were specified in the solid samples, and the content of soluble nitrogen was determined in the extracts. These data were used to calculate the efficiency of extraction of nitrogen-containing compounds. The coagulation activity was assessed by jar test using synthetic turbid water, of the initial pH 9 and turbidity 35 NTU. The jar test was carried out by adding different amounts of extracts to model water, and stirring the content. After sedimentation for 1 h, residual turbidity was determined by turbidimeter and coagulation activity was calculated. The increment of organic matter concentration after the coagulation was also determined. These experiments confirmed that extracts of all investigated strains of bean could be used successfully as natural coagulants.

  5. Results of a phase I/II open-label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients.

    Science.gov (United States)

    Martinowitz, U; Lissitchkov, T; Lubetsky, A; Jotov, G; Barazani-Brutman, T; Voigt, C; Jacobs, I; Wuerfel, T; Santagostino, E

    2015-11-01

    rIX-FP is a coagulation factor IX (recombinant), albumin fusion protein with more than fivefold half-life prolongation over other standard factor IX (FIX) products available on the market. This prospective phase II, open-label study evaluated the safety and efficacy of rIX-FP for the prevention of bleeding episodes during weekly prophylaxis and assessed the haemostatic efficacy for on-demand treatment of bleeding episodes in previously treated patients with haemophilia B. The study consisted of a 10-14 day evaluation of rIX-FP pharmacokinetics (PK), and an 11 month safety and efficacy evaluation period with subjects receiving weekly prophylaxis treatment. Safety was evaluated by the occurrence of related adverse events, and immunogenic events, including development of inhibitors. Efficacy was evaluated by annualized spontaneous bleeding rate (AsBR), and the number of injections to achieve haemostasis. Seventeen subjects participated in the study, 13 received weekly prophylaxis and 4 received episodic treatment only. No inhibitors were detected in any subject. The mean and median AsBR were 1.25, and 1.13 respectively in the weekly prophylaxis arm. All bleeding episodes were treated with 1 or 2 injections of rIX-FP. Three prophylaxis subjects who were treated on demand prior to study entry had >85% reduction in AsBR compared to the bleeding rate prior to study entry. This study demonstrated the efficacy for weekly routine prophylaxis of rIX-FP to prevent spontaneous bleeding episodes and for the treatment of bleeding episodes. In addition no safety issues were detected during the study and an improved PK profile was demonstrated. © 2015 CSL Behring. Haemophilia published by John Wiley & Sons Ltd.

  6. Health economics of treating haemophilia A with inhibitors.

    Science.gov (United States)

    Knight, C

    2005-11-01

    Haemophilia is a rare, inherited blood disorder in which blood clotting is impaired such that patients suffer from excessive internal and external bleeding. At present there is no cure for haemophilia A and patients require expensive, life-long treatment involving clotting factor replacement therapy. Treatment costs are perceived to be higher for patients who have developed inhibitory antibodies to factor VIII, the standard therapy for haemophilia A. However, initial cost analyses suggest that clotting factor therapy with alternative haemostatic agents, such as recombinant activated factor VII or activated prothrombin complex concentrate, is no more expensive for the majority of haemophilia A patients with inhibitors than for those without inhibitors. With the availability of effective alternative haemostatic agents, orthopaedic surgery for haemophilia A patients with inhibitors is now a clinical option, and initial cost analyses suggest this may be a cost-effective treatment strategy for patients with inhibitors whose quality of life (QoL) is severely impaired by joint arthropathy. In an era of finite healthcare resourcing it is important to determine whether new treatments justify higher unit costs compared with standard therapies and whether such higher costs are justified from an individual perspective in terms of improved QoL, and from a societal perspective in terms of improved productivity and reduced overall healthcare costs. This paper examines current data on the health economics of treating haemophilia A patients with inhibitors, focusing on the overall costs of clotting factor replacement therapy and the cost consequences of joint replacement.

  7. Coagulation management in patients undergoing neurosurgical procedures.

    Science.gov (United States)

    Robba, Chiara; Bertuetti, Rita; Rasulo, Frank; Bertuccio, Alessando; Matta, Basil

    2017-10-01

    Management of coagulation in neurosurgical procedures is challenging. In this contest, it is imperative to avoid further intracranial bleeding. Perioperative bleeding can be associated with a number of factors, including anticoagulant drugs and coagulation status but is also linked to the characteristic and the site of the intracranial disorder. The aim of this review will be to focus primarily on the new evidence regarding the management of coagulation in patients undergoing craniotomy for neurosurgical procedures. Antihemostatic and anticoagulant drugs have shown to be associated with perioperative bleeding. On the other hand, an increased risk of venous thromboembolism and hypercoagulative state after elective and emergency neurosurgery, in particular after brain tumor surgery, has been described in several patients. To balance the risk between thrombosis and bleeding, it is important to be familiar with the perioperative changes in coagulation and with the recent management guidelines for anticoagulated patients undergoing neurosurgical procedures, in particular for those taking new direct anticoagulants. We have considered the current clinical trials and literature regarding both safety and efficacy of deep venous thrombosis prophylaxis in the neurosurgical population. These were mainly trials concerning both elective surgical and intensive care patients with a poor grade intracranial bleed or multiple traumas with an associated severe traumatic brain injury (TBI). Coagulation management remains a major issue in patients undergoing neurosurgical procedures. However, in this field of research, literature quality is poor and further studies are necessary to identify the best strategies to minimize risks in this group of patients.

  8. Tissue Factor and Tissue Factor Pathway Inhibitor in the Wound-Healing Process After Neurosurgery.

    Science.gov (United States)

    Ślusarz, Robert; Głowacka, Mariola; Biercewicz, Monika; Barczykowska, Ewa; Haor, Beata; Rość, Danuta; Gadomska, Grażyna

    2016-03-01

    The aim of the study was to assess the concentrations of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the blood of patients with a postoperative wound after neurosurgery. Participants included 20 adult patients who underwent neurosurgery because of degenerative spine changes. The concentration of TF and TFPI in the patients' blood serum was measured 3 times: before surgery, during the first 24 hr after surgery, and between the 5th and 7th days after surgery. The control group comprised 20 healthy volunteers similar to the patient group with respect to gender and age. A statistically significant difference was observed between TF concentration at all three measurement time points in the research group and TF concentration in the control group (p = .018, p = .010, p = .001). A statistically significant difference was found between TFPI concentration at the second time point in the research group and TFPI concentration in the control group (p = .041). No statistically significant within-subject difference was found between TF concentrations before and after surgery. A statistically significant within-subject difference was found between TFPI concentrations within 24 hr after surgery and 5-7 days after surgery (p = .004). High perioperative concentrations of TF indicate not only the presence of thrombophilia but also the importance of TF in the wound-healing process. Perioperative changes in TFPI concentrations are related to its compensatory influence on hemostasis in thrombophilic conditions. © The Author(s) 2015.

  9. Squash inhibitor family of serine proteinases

    International Nuclear Information System (INIS)

    Otlewski, J.; Krowarsch, D.

    1996-01-01

    Squash inhibitors of serine proteinases form an uniform family of small proteins. They are built of 27-33 amino-acid residues and cross-linked with three disulfide bridges. The reactive site peptide bond (P1-P1') is between residue 5 (Lys, Arg or Leu) and 6 (always Ile). High resolution X-ray structures are available for two squash inhibitors complexed with trypsin. NMR solution structures have also been determined for free inhibitors. The major structural motif is a distorted, triple-stranded antiparallel beta-sheet. A similar folding motif has been recently found in a number of proteins, including: conotoxins from fish-hunting snails, carboxypeptidase inhibitor from potato, kalata B1 polypeptide, and in some growth factors (e.g. nerve growth factor, transforming growth factor β2, platelet-derived growth factor). Squash inhibitors are highly stable and rigid proteins. They inhibit a number of serine proteinases: trypsin, plasmin, kallikrein, blood clotting factors: X a and XII a , cathepsin G. The inhibition spectrum can be much broadened if specific amino-acid substitutions are introduced, especially at residues which contact proteinase. Squash inhibitors inhibit proteinases via the standard mechanism. According to the mechanism, inhibitors are substrates which exhibit at neutral pH a high k cat /K m index for hydrolysis and resynthesis of the reactive site, and a low value of the hydrolysis constant. (author)

  10. Isolation, cloning and structural characterisation of boophilin, a multifunctional Kunitz-type proteinase inhibitor from the cattle tick.

    Directory of Open Access Journals (Sweden)

    Sandra Macedo-Ribeiro

    Full Text Available Inhibitors of coagulation factors from blood-feeding animals display a wide variety of structural motifs and inhibition mechanisms. We have isolated a novel inhibitor from the cattle tick Boophilus microplus, one of the most widespread parasites of farm animals. The inhibitor, which we have termed boophilin, has been cloned and overexpressed in Escherichia coli. Mature boophilin is composed of two canonical Kunitz-type domains, and inhibits not only the major procoagulant enzyme, thrombin, but in addition, and by contrast to all other previously characterised natural thrombin inhibitors, significantly interferes with the proteolytic activity of other serine proteinases such as trypsin and plasmin. The crystal structure of the bovine alpha-thrombin.boophilin complex, refined at 2.35 A resolution reveals a non-canonical binding mode to the proteinase. The N-terminal region of the mature inhibitor, Q16-R17-N18, binds in a parallel manner across the active site of the proteinase, with the guanidinium group of R17 anchored in the S(1 pocket, while the C-terminal Kunitz domain is negatively charged and docks into the basic exosite I of thrombin. This binding mode resembles the previously characterised thrombin inhibitor, ornithodorin which, unlike boophilin, is composed of two distorted Kunitz modules. Unexpectedly, both boophilin domains adopt markedly different orientations when compared to those of ornithodorin, in its complex with thrombin. The N-terminal boophilin domain rotates 9 degrees and is displaced by 6 A, while the C-terminal domain rotates almost 6 degrees accompanied by a 3 A displacement. The reactive-site loop of the N-terminal Kunitz domain of boophilin with its P(1 residue, K31, is fully solvent exposed and could thus bind a second trypsin-like proteinase without sterical restraints. This finding explains the formation of a ternary thrombin.boophilin.trypsin complex, and suggests a mechanism for prothrombinase inhibition in vivo.

  11. Coagulation profile in patients undergoing video-assisted thoracoscopic lobectomy: A randomized, controlled trial.

    Directory of Open Access Journals (Sweden)

    Thomas Decker Christensen

    Full Text Available Knowledge about the impact of Low-Molecular-Weight Heparin (LMWH on the coagulation system in patients undergoing minimal invasive lung cancer surgery is sparse. The aim of this study was to assess the effect of LMWH on the coagulation system in patients undergoing Video-Assisted Thoracoscopic Surgery (VATS lobectomy for primary lung cancer.Sixty-three patients diagnosed with primary lung cancer undergoing VATS lobectomy were randomized to either subcutaneous injection with dalteparin (Fragmin® 5000 IE once daily or no intervention. Coagulation was assessed pre-, peri-, and the first two days postoperatively by standard coagulation blood test, thromboelastometry (ROTEM® and thrombin generation.Patients undergoing potential curative surgery for lung cancer were not hypercoagulable preoperatively. There was no statistically significant difference in the majority of the assessed coagulation parameters after LMWH, except that the no intervention group had a higher peak thrombin and a shorter INTEM clotting time on the first postoperative day and a lower fibrinogen level on the second postoperative day. A lower level of fibrin d-dimer in the LMWH group was found on the 1. and 2.postoperative day, although not statistical significant. No differences were found between the two groups in the amount of bleeding or number of thromboembolic events.Use of LMWH administered once daily as thromboprophylaxis did not alter the coagulation profile per se. As the present study primarily evaluated biochemical endpoints, further studies using clinical endpoints are needed in regards of an optimized thromboprophylaxis approach.

  12. Evaluation of the process of coagulation/flocculation of produced water using Moringa oleifera Lam. as natural coagulant

    Energy Technology Data Exchange (ETDEWEB)

    Santana, C.R.; Pereira, D.F.; Sousa, S.C S N.; Silva, G.F. [Universidade Federal de Sergipe (UFSE), Sao Cristovao, SE (Brazil). Dept. de Engenharia Quimica], e-mail: claudia@ufs.br; Cavalcanti, E.B. [Universidade Tiradentes (UNIT), SE (Brazil). Inst. de Tecnologia e Pesquisa

    2010-07-15

    In the lifetime of an oil well, there comes a moment when a lot of water begins to be produced along with oil, either by the conditions of the reservoir, or as a result of water injection in the secondary recovery of the well. An important step in such process involves the treatment of the produced water by means of coagulation techniques. Therefore, the use of environmentally correct coagulants is presented as a viable alternative and has demonstrated advantages over the use of chemical coagulants. The plant of the genus Moringa, whose species is oleifera Lam, stands out as one of the most promising natural coagulants. The present study investigated the evaluation of the coagulation/flocculation of produced water, using seeds of Moringa oleifera Lam. as coagulant. The results were very significant, demonstrating that Moringa oleifera Lam. can be used as a natural coagulant in this type of treatment. (author)

  13. 凝血检验、血常规的影响因素及控制变异方法分析%The analysis of coagulation tests, blood routine test inlfuence factors and the variation control method

    Institute of Scientific and Technical Information of China (English)

    黄祥丽; 代治国

    2016-01-01

    目的:探讨凝血检验及血常规分析的影响因素及控制变异方法。方法选取2015年1~5月本院招募的健康成年志愿者60名,行凝血常规和血常规检测,对检测结果进行统计分析。结果压脉带使用3分钟时的活化部分凝血活酶时间(activated partial thromboplastin time,APTT)、凝血酶时间(thrombin time,TT)和凝血酶原时间(prothrombin time,PT)分别为(24.60±1.85)秒、(16.54±4.18)秒和(9.80±2.96)秒,均明显低于压脉带即刻时水平,差异有显著性(P<0.05)。压脉带使用3分钟时的红细胞(red blood cell,RBC)和血红蛋白(hemoglobin,HGB)分别为(5.28±0.64)×1012/L和(155.97±6.75)g/L,均明显高于压脉带即刻时水平,白细胞(white blood cell,WBC)和血小板(blood platelet,PLT)分别为(4.26±0.28)×109/L和(172.16±8.95)×109/L。离心前后放置2小时APTT分别为(37.18±2.68)秒和(30.05±3.19)秒,差异有显著性(P<0.05),而血浆纤维蛋白原(plasma fibrinogen,FIB)、TT和PT差异无显著性(P>0.05);离心前后放置4小时APTT、TT和PT差异有显著性(P<0.05)。标本放置24小时后RBC和PLT分别为(4.17±0.30)×1012/L和(165.29±5.58)×109/L,明显低于其他放置时间点,而WBC为(5.32±0.26)×109/L,高于其他放置时间点,差异有显著性(P<0.05)。结论标本采集和标本放置时间及方式对凝血检验及血常规分析有影响,重视控制变异方法,能极大提高检测数据可靠性。%Objective To investigate coagulation tests, blood routine test influence factors and the variation control method.Method60 healthy adult volunteers had been recruited in our hospital from January 2015 to May 2015, for blood coagulation and blood routine examination, the results were statistically analyzed.ResultPressure pulse belt used 3 minutes of activated partial thromboplastin time

  14. Recombinant epidermal growth factor-like domain-1 from coagulation factor VII functionalized iron oxide nanoparticles for targeted glioma magnetic resonance imaging.

    Science.gov (United States)

    Liu, Heng; Chen, Xiao; Xue, Wei; Chu, Chengchao; Liu, Yu; Tong, Haipeng; Du, Xuesong; Xie, Tian; Liu, Gang; Zhang, Weiguo

    The highly infiltrative and invasive nature of glioma cells often leads to blurred tumor margins, resulting in incomplete tumor resection and tumor recurrence. Accurate detection and precise delineation of glioma help in preoperative delineation, surgical planning and survival prediction. In this study, recombinant epidermal growth factor-like domain-1, derived from human coagulation factor VII, was conjugated to iron oxide nanoparticles (IONPs) for targeted glioma magnetic resonance (MR) imaging. The synthesized EGF1-EGFP-IONPs exhibited excellent targeting ability toward tissue factor (TF)-positive U87MG cells and human umbilical vein endothelial cells in vitro, and demonstrated persistent and efficient MR contrast enhancement up to 12 h for preclinical glioma models with high targeting specificity in vivo. They hold great potential for clinical translation and developing targeted theranostics against brain glioma.

  15. Dietary changes in fasting levels of factor VII coagulant activity (FVII:C) are accompanied by changes in factor VII protein and other vitamin K-dependent proteins

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Tholstrup, T; Marckmann, P

    1995-01-01

    The mechanisms behind dietary effects on fasting coagulant activity of factor VII (FVII:C) are not clarified. In the present study of 15 young volunteers, two experimental diets differing in composition of saturated fatty acids (C18:0 [diet S] or C12:0 + C14:0 [diet ML]) were served for 3 weeks...

  16. Optimum coagulant forecasting by modeling jar test experiments using ANNs

    Science.gov (United States)

    Haghiri, Sadaf; Daghighi, Amin; Moharramzadeh, Sina

    2018-01-01

    Currently, the proper utilization of water treatment plants and optimizing their use is of particular importance. Coagulation and flocculation in water treatment are the common ways through which the use of coagulants leads to instability of particles and the formation of larger and heavier particles, resulting in improvement of sedimentation and filtration processes. Determination of the optimum dose of such a coagulant is of particular significance. A high dose, in addition to adding costs, can cause the sediment to remain in the filtrate, a dangerous condition according to the standards, while a sub-adequate dose of coagulants can result in the reducing the required quality and acceptable performance of the coagulation process. Although jar tests are used for testing coagulants, such experiments face many constraints with respect to evaluating the results produced by sudden changes in input water because of their significant costs, long time requirements, and complex relationships among the many factors (turbidity, temperature, pH, alkalinity, etc.) that can influence the efficiency of coagulant and test results. Modeling can be used to overcome these limitations; in this research study, an artificial neural network (ANN) multi-layer perceptron (MLP) with one hidden layer has been used for modeling the jar test to determine the dosage level of used coagulant in water treatment processes. The data contained in this research have been obtained from the drinking water treatment plant located in Ardabil province in Iran. To evaluate the performance of the model, the mean squared error (MSE) and correlation coefficient (R2) parameters have been used. The obtained values are within an acceptable range that demonstrates the high accuracy of the models with respect to the estimation of water-quality characteristics and the optimal dosages of coagulants; so using these models will allow operators to not only reduce costs and time taken to perform experimental jar tests

  17. Kinetic modeling sheds light on the mode of action of recombinant factor VIIa on thrombin generation.

    Science.gov (United States)

    Mitrophanov, Alexander Y; Reifman, Jaques

    2011-10-01

    The therapeutic potential of a hemostatic agent can be assessed by investigating its effects on the quantitative parameters of thrombin generation. For recombinant activated factor VII (rFVIIa)--a promising hemostasis-inducing biologic--experimental studies addressing its effects on thrombin generation yielded disparate results. To elucidate the inherent ability of rFVIIa to modulate thrombin production, it is necessary to identify rFVIIa-induced effects that are compatible with the available biochemical knowledge about thrombin generation mechanisms. The existing body of knowledge about coagulation biochemistry can be rigorously represented by a computational model that incorporates the known reactions and parameter values constituting the biochemical network. We used a thoroughly validated numerical model to generate activated factor VII (FVIIa) titration curves in the cases of normal blood composition, hemophilia A and B blood, blood lacking factor VII, blood lacking tissue factor pathway inhibitor, and diluted blood. We utilized the generated curves to perform systematic fold-change analyses for five quantitative parameters characterizing thrombin accumulation. The largest fold changes induced by increasing FVIIa concentration were observed for clotting time, thrombin peak time, and maximum slope of the thrombin curve. By contrast, thrombin peak height was much less affected by FVIIa titrations, and the area under the thrombin curve stayed practically unchanged. Comparisons with experimental data demonstrated that the computationally derived patterns can be observed in vitro. rFVIIa modulates thrombin generation primarily by accelerating the process, without significantly affecting the total amount of generated thrombin. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Enhanced coagulation for improving coagulation performance and reducing residual aluminum combining polyaluminum chloride with diatomite.

    Science.gov (United States)

    Hu, Wenchao; Wu, Chunde

    2016-01-01

    The feasibility of using enhanced coagulation, which combined polyaluminum chloride (PAC) with diatomite for improving coagulation performance and reducing the residual aluminum (Al), was discussed. The effects of PAC and diatomite dosage on the coagulation performance and residual Al were mainly investigated. Results demonstrated that the removal efficiencies of turbidity, dissolved organic carbon (DOC), and UV254 were significantly improved by the enhanced coagulation, compared with PAC coagulation alone. Meaningfully, the five forms of residual Al (total Al (TAl), total dissolved Al (TDAl), dissolved organic Al (DOAl), dissolved monomeric Al (DMAl), and dissolved organic monomeric Al (DOMAl)) all had different degrees of reduction in the presence of diatomite and achieved the lowest concentrations (0.185, 0.06, 0.053, 0.014, and 0 mg L(-1), respectively) at a PAC dose of 15 mg L(-1) and diatomite dose of 40 mg L(-1). In addition, when PAC was used as coagulant, the majority of residual Al existed in dissolved form (about 31.14-70.16%), and the content of DOMAl was small in the DMAl.

  19. [Effect on the microbicidal efficacy of formaldehyde, glutardialdehyde, peracetic acid, chloramine T (N-chloro-4-toluenesulfonamide), m-cresol, ethanol and benzyldimethyldodecacylammonium bromide by blood (model experiments for chemical disinfection of instruments)].

    Science.gov (United States)

    Spicher, G; Peters, J

    1998-02-01

    In a preceding paper (Zbl. Hyg. 191 [1991] 457-477) we reported on the dependence of the microbicidal efficacy of active agents of the disinfection of instruments on the amount of coagulated blood adhering to the instruments. In the present investigation, we were interested in the dependence of the microbicidal effects on the amount of blood in the solutions of the active agents. Test areas of 2 cm2 were contaminated with 50 and 100 microliters coagulating blood, respectively, containing cells of Staphylococcus aureus as test germ. The solutions of the microbicidal agents were contaminated with heparinized blood up to a concentration of 4% immediately before starting the disinfection and 24 hours before, respectively. After a period of action lasting 1 hour at 20 degrees C, the relative number of test germs capable of multiplying (N/N0) was determined. The concentration of the microbicidal substances reducing the relative number of test germs capable to multiply to 10(-4) served for estimating the dependence of the microbicidal efficacy of the agents on the blood content of the solutions. The experimental results depended on the thickness of the layer of coagulated blood. The dependence of the efficacy of the microbicidal substances on the blood content of the solutions was the higher the thinner the blood layer was. At a thickness of the layer of the coagulated blood of 0.25 mm, a blood content of the solution of 4%, and applying it immediately after adding the blood, the concentration of glutardialdehyde had to be 1.6 times that without blood to reach the same microbicidal efficacy. When applying the solution 24 hours after adding the blood, the concentration of glutardialdehyde had to be 4.2 times that without blood. The quaternary ammonium compound reacted faster with the blood than did glutardialdehyde; the respective factors were 2.6 and 4.5. The concentration factors of chloramine T were 3.3 and 3.8. Under the conditions of the test, peracetic acid exhibited

  20. Gamma-secretase inhibitor treatment promotes VEGF-A-driven blood vessel growth and vascular leakage but disrupts neovascular perfusion.

    Directory of Open Access Journals (Sweden)

    Mattias Kalén

    Full Text Available The Notch signaling pathway is essential for normal development due to its role in control of cell differentiation, proliferation and survival. It is also critically involved in tumorigenesis and cancer progression. A key enzyme in the activation of Notch signaling is the gamma-secretase protein complex and therefore, gamma-secretase inhibitors (GSIs--originally developed for Alzheimer's disease--are now being evaluated in clinical trials for human malignancies. It is also clear that Notch plays an important role in angiogenesis driven by Vascular Endothelial Growth Factor A (VEGF-A--a process instrumental for tumor growth and metastasis. The effect of GSIs on tumor vasculature has not been conclusively determined. Here we report that Compound X (CX, a GSI previously reported to potently inhibit Notch signaling in vitro and in vivo, promotes angiogenic sprouting in vitro and during developmental angiogenesis in mice. Furthermore, CX treatment suppresses tumor growth in a mouse model of renal carcinoma, leads to the formation of abnormal vessels and an increased tumor vascular density. Using a rabbit model of VEGF-A-driven angiogenesis in skeletal muscle, we demonstrate that CX treatment promotes abnormal blood vessel growth characterized by vessel occlusion, disrupted blood flow, and increased vascular leakage. Based on these findings, we propose a model for how GSIs and other Notch inhibitors disrupt tumor blood vessel perfusion, which might be useful for understanding this new class of anti-cancer agents.

  1. Development of High Temperature Short Time Vertebrate-Blood Pasteurization Equipment for Tsetse Fly Diets

    Energy Technology Data Exchange (ETDEWEB)

    Moravek, I; Lach, J [Department of Manufacturing Systems, Slovak Technical University Namestie Slobody 17 812 31 Bratislava (Slovakia); Takac, P [Institute of Zoology, SAV, Bratislava (Slovakia)

    2012-07-15

    Tsetse flies feed only on vertebrate blood, but the collection and processing of blood is expensive, it must be stored at -20{sup o}C requiring costly storage rooms and reliable electricity, and it must be irradiated to reduce bacterial contamination. This is tolerable for small colonies, but as colony size increases to service large- scale programmes, the supply and processing of blood becomes critical. Blood is normally collected from cattle at slaughter. This process is necessarily not aseptic, and large-scale collection is only possible where the animals are suspended for bleeding. One alternative to blood decontamination is using the High Temperature Short time Pasteurization (HTST) method. The food processing industry uses pasteurization to reduce bacterial load in a wide range of products. Our previous results indicated that for the control of the blood pasteurization process, to reach satisfactory bacteriological purity and at the same time to prevent the blood from coagulating, it is important to study temperature and time and also some other parameters that could predict blood coagulation. Crucial for blood coagulation is to study blood viscosity. Classical heat exchangers are not suitable for blood pasteurization. In such equipment the blood coagulation depends on temperature and time. Besides the relatively low temperatures, blood is coagulating with cumulative time until total shutdown of blood flow. After a series of experiments we found a solution using microwave systems. To verify the microwave heating concept, we built an experimental workstation. First we verified the accuracy of the applicator design from the aspect of output adaptation to the power source. Also we installed measuring equipment. This system complies with the requirements of quick heating with sufficiently high heat accumulation. By utilizing standard components for the base of the microwave generator, it is possible to markedly reduce the final price of the equipment. (author)

  2. Blood coagulation factor VIII: An overview

    Indian Academy of Sciences (India)

    Unknown

    Solvent, detergent and heat treatment. Hemofil-M. Baxter. Pooled human venous plasma. Immunoaffinity chromatography using murine monoclonal anti- body. Solvent and detergent. Monarc-M. American. Red Cross. Pooled human venous plasma. Immunoaffinity chromatography using murine monoclonal antibody.

  3. Acquired high titre factor VIII inhibitor with underlying polyarteritis nodosa.

    Science.gov (United States)

    Snowden, J A; Hutchings, M; Spearing, R; Patton, W N

    1997-05-01

    We here present the case of a 70-year-old woman referred to our unit for investigation of bleeding. Investigations confirmed a high titre acquired Factor VIII inhibitor. In association there was relapse of systemic illness associated with anti-neutrophil cytoplasmic antibodies (atypical pattern) for which she had been treated five years previously. Immunosuppression was attempted, but it failed to have an impact both on the inhibitor titre and on the underlying disorder. The patient died from multi-organ failure and massive chest hemorrhage. Post-mortem showed necrotizing vasculitis of medium sized vessels at several sites, including the kidney, consistent with a diagnosis of polyarteritis nodosa. Although it is well recognised that Factor VIII inhibitors are found in conjunction with autoimmune disorders, this case is significant in that it is the first associated with histologically proven polyarteritis nodosa type vasculitis. The case illustrates the difficulties in the investigation and management of patients with acquired high titre Factor VIII inhibitors.

  4. Microwave coagulation therapy and drug injection to treat splenic injury.

    Science.gov (United States)

    Zhang, Guoming; Sun, Yuanyuan; Yu, Jie; Dong, Lei; Mu, Nannan; Liu, Xiaohong; Liu, Lanfen; Zhang, Yan; Wang, Xiaofei; Liang, Ping

    2014-01-01

    The present study compares the efficacy of 915- and 2450-MHz contrast-enhanced ultrasound (CEUS)-guided percutaneous microwave coagulation with that of CEUS-guided thrombin injection for the treatment of trauma-induced spleen hemorrhage. In a canine splenic artery hemorrhage model with two levels of arterial diameter (A, microwaves and drug injection. Therapy efficacy was measured by comparing bleeding rate, hemostatic time, bleeding index, bleeding volume, and pathology. The most efficient technique was CEUS-guided 915-MHz percutaneous microwave coagulation therapy in terms of action time and total blood loss. The success rate of the 915-MHz microwave group was higher than that of the 2450-MHz microwave and the drug injection groups (except A level, P microwave group than those in the 2450-MHz microwave and drug injection groups (P microwave group, but pathologic changes of light injury could be seen in the other groups. The present study provides evidence that microwave coagulation therapy is more efficient than thrombin injection for the treatment of splenic hemorrhage. Furthermore, treatment with 915-MHz microwaves stops bleeding more rapidly and generates a wider cauterization zone than does treatment with 2450-MHz microwaves. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Haemostasis – issue always up todate

    Directory of Open Access Journals (Sweden)

    Eliza Pleban

    2015-06-01

    Full Text Available Haemostasis is a set of processes with the aim to maintain blood in the liquid state in the vascular bed, and in the case of damage to the vessel – to prevent extravasation by clot formation (initially a platelet clot and then a fibrin clot. The main components of haemostasis include: platelets, vessel wall, plasma coagulation system, endogenous inhibitors of coagulation and fibrinolytic system. The stream of blood is also an important factor. Haemostasis is divided into two main phases: coagulation and fibrinolysis. These two phases take place simultaneously and remain in equilibrium. The prevalence of any of these processes is the result of the advantage of enzyme complex activity over the complex of the other process. In everyday practice, every physician encounters drugs that affect haemostasis. At the end of the article, the most commonly used anticoagulants and antiplatelet agents available in Poland are described with the mechanisms of their action. The effect of oral anticoagulants results from the inhibition of the transformation of vitamin K1 which is essential for the production of coagulation factors II, VII, IX and X. Acenocoumarol and warfarin are currently available in Poland. The group of new oral anticoagulants includes direct inhibitors of activated factor X: rivaroxaban, apixaban and dabigatran – a potent, competitive and reversible direct thrombin inhibitor. Anticoagulants which are used parenterally include unfractionated heparin, low molecular weight heparins and fondaparinux. Antiplatelet drugs can be divided into two groups based on the mechanism of action – drugs acting through the metabolism of arachidonic acid (aspirin and acting on the platelet membrane receptors (ticlopidine, clopidogrel and prasugrel.

  6. How to distinguish between bleeding and coagulated extradural hematomas on the plain CT scanning

    International Nuclear Information System (INIS)

    Petersen, O.F.; Espersen, J.O.

    1984-01-01

    Four types of extradural hematoma could be separated at examination of the plain CT scan in 54 extradural hematomas. Two major groups appear: the still bleeding hematoma showing either generally low attenuation values of ''holes'', and a coagulated homogenous type with generally high attenuation values. The attenuation values of the bleeding-liquid part of hematoma - were correlated to hemoglobin concentration in blood, to which clots were not related. Seven extradural hematomas grew and coagulated on repeated preoperative CT scans. In two cases intravenous contrast was given to the bleeding type of hematoma, and the contrast media appeared in ''holes'', but not in areas of high attenuation value. It is easy to distinguish between the different types of hematoma on the plain CT scan, and the separation by eye between the still bleeding and the coagulated extradural hematoma seems reliable. (orig.)

  7. Recombinant-activated factor VII in patients with uncontrolled bleeding: A retrospective observational analysis

    Directory of Open Access Journals (Sweden)

    Said D Abuhasna

    2012-01-01

    Full Text Available Background: Factor VIIa (recombinant has an off-label use to control life-threatening bleeding that is refractory to other measures and was shown to decrease transfusion requirements. Objective: The primary objective of this study was to assess the safety and effectiveness of factor VIIa (recombinant on blood transfusion requirements and coagulation parameters when used in patients whose bleeding was uncorrected by other means. The pharmacoeconomic impact for any discrepancy from our protocol was evaluated. Secondary outcomes included 4-hour and 28-day mortality, as well as safety of this agent in terms of thromboembolic complications. Materials and Methods: We retrospectively evaluated patients who received recombinant-activated factor VII (rFVIIa for uncontrolled bleeding from June 2008 to April 2011. The medical records of 33 patients were evaluated. Coagulation parameters and blood products were determined 24 hours before and 24 hours after administration of rFVIIa, and the results compared. Patients were also screened for any thromboembolic complications. Results: Administration of rFVIIa reduced blood transfusion requirements and improved coagulation parameters significantly (P<0.05. No thromboembolic complications were reported. Most of the dosing was consistent with those recommended in our institutional protocol, with discrepancies resulting in an average cost of $56 058. Moreover, pH was reported in only 67% of patients. All patients treated with rFVIIa survived up to 4 hours after receiving this agent, while the 28-day mortality was 24% (8/33. Conclusion: The use of rFVIIa appears to be safe and effective in promoting hemostasis, as evident from reducing transfusion requirements and improving the coagulation variables.

  8. Peculiarities of coagulation hemostasis disorders in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Yakovlieva V.H.

    2015-09-01

    Full Text Available The violation of blood coagulation properties is observed in many diseases of the respiratory system, including chronic obstructive pulmonary disease (COPD. It is known that in a stable COPD phase release of proinflammatory cytokines in blood is observed, it leads to disturbance of hemostasis parameters toward hypercoagulation. The aim of our study was to determine possibility of coagulation disorders formation in patients with COPD in a stable phase of pathological process at different stages of disease course and identify relationship between coagulation parameters levels and degree of violation of ventilation lung function. Materials and methods. We examined 30 patients with COPD in a stable disease phase, included in the main group (FEV1 =49,5±15,5% of the due, there were 27 men (90.0%, 3 (30.0% women, mean age was 61,8±7,9 years, level of pack /years index - 34,2±15,3. The control group consisted of 10 healthy subjects matched with the patients of the main group by age and sex. All patients were divided into 2 subgroups. Subgroup 1 included 16 patients with moderate COPD, that is the level of FEV1>50% (61,8±7,4% of predicted, and subgroup 2 - 14 COPD patients with severe COPD, that is the level of FEV1 <50% (35,3±8,2% of predicted. Patients received standard treatment according to the disease stage. Main indicators of coagulation levels: prothrombin index (PI, prothrombin ratio (PR, international normalized ratio (INR, activated partial thromboplastin time (APTT, thrombin time (TT and antithrombin III (AT III were identified in all patients. Results. The levels of PI, PR and INR in the subgroup 1 differed significantly from those of in the subgroup 2, control group (p<0,05 and pointed at hypercoagulation, whereas in the subgroup 2 all indicators were absolutely identical with control group. Correlation link between the level of INR levels and FEV1 (r=-0,73; p<0.01 in patients of the main group was determined. Levels of APTT, TT and AT

  9. Damage control resuscitation using blood component therapy in standard doses has a limited effect on coagulopathy during trauma hemorrhage.

    Science.gov (United States)

    Khan, Sirat; Davenport, Ross; Raza, Imran; Glasgow, Simon; De'Ath, Henry D; Johansson, Pär I; Curry, Nicola; Stanworth, Simon; Gaarder, Christine; Brohi, Karim

    2015-02-01

    To determine the effectiveness of blood component therapy in the correction of trauma-induced coagulopathy during hemorrhage. Severe hemorrhage remains a leading cause of mortality in trauma. Damage control resuscitation strategies target trauma-induced coagulopathy (TIC) with the early delivery of high-dose blood components such as fresh frozen plasma (FFP) and platelet transfusions. However, the ability of these products to correct TIC during hemorrhage and resuscitation is unknown. This was an international prospective cohort study of bleeding trauma patients at three major trauma centers. A blood sample was drawn immediately on arrival and after 4, 8 and 12 packed red blood cell (PRBC) transfusions. FFP, platelet and cryoprecipitate use was recorded during these intervals. Samples were analyzed for functional coagulation and procoagulant factor levels. One hundred six patients who received at least four PRBC units were included. Thirty-four patients (32 %) required a massive transfusion. On admission 40 % of patients were coagulopathic (ROTEM CA5 ≤ 35 mm). This increased to 58 % after four PRBCs and 81 % after eight PRBCs. On average all functional coagulation parameters and procoagulant factor concentrations deteriorated during hemorrhage. There was no clear benefit to high-dose FFP therapy in any parameter. Only combined high-dose FFP, cryoprecipitate and platelet therapy with a high total fibrinogen load appeared to produce a consistent improvement in coagulation. Damage control resuscitation with standard doses of blood components did not consistently correct trauma-induced coagulopathy during hemorrhage. There is an important opportunity to improve TIC management during damage control resuscitation.

  10. Enhanced algae removal by Ti-based coagulant: comparison with conventional Al- and Fe-based coagulants.

    Science.gov (United States)

    Xu, Jie; Zhao, Yanxia; Gao, Baoyu; Zhao, Qian

    2018-05-01

    The water eutrophication caused by cyanobacteria seasonally proliferates, which is a hot potato to be resolved for water treatment plants. This study firstly investigated coagulation performance of titanium tetrachloride (TiCl 4 ) for Microcystis aeruginosa synthetic water treatment. Results show complete algal cell removal by TiCl 4 coagulation without damage to cell membrane integrity even under harsh conditions; 60 mg/L TiCl 4 was effective in removing the microcystins up to 85%. Furthermore, besides having stronger UV 254 removal capability and the higher removal of fluorescent substances over Al- and Fe-based coagulants, TiCl 4 coagulant required more compact coagulation and sedimentation tanks due to its significantly improved floc growth and sedimentation speed. Meanwhile, its' short hydraulic retention time avoided algal cell breakage and subsequent algal organic matter release. Microcystin concentrations were kept at a low level during sludge storage period, indicating that the TiCl 4 flocs could prevent algal cells from natural lysis. To facilitate water recycling without secondary contamination, the algae-containing sludge after TiCl 4 coagulation ought to be disposed within 12 days at 20 °C and 8 days at 35 °C.

  11. Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

    Directory of Open Access Journals (Sweden)

    Nicholas B. Abt

    2014-01-01

    Full Text Available Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable. Methods. The patient’s plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours. Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity. Conclusions. Physicians can be presented with the challenging clinical picture of an acquired factor VIII inhibitor without a detectable inhibitor by the Bethesda assay. Standard therapy for an acquired hemophilia A should be considered.

  12. Polyphenol Compound as a Transcription Factor Inhibitor.

    Science.gov (United States)

    Park, Seyeon

    2015-10-30

    A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor-DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein-protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1), c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and β-catenin/T cell factor (Tcf)).

  13. Dust coagulation in ISM

    Science.gov (United States)

    Chokshi, Arati; Tielens, Alexander G. G. M.; Hollenbach, David

    1989-01-01

    Coagulation is an important mechanism in the growth of interstellar and interplanetary dust particles. The microphysics of the coagulation process was theoretically analyzed as a function of the physical properties of the coagulating grains, i.e., their size, relative velocities, temperature, elastic properties, and the van der Waal interaction. Numerical calculations of collisions between linear chains provide the wave energy in individual particles and the spectrum of the mechanical vibrations set up in colliding particles. Sticking probabilities are then calculated using simple estimates for elastic deformation energies and for the attenuation of the wave energy due to absorption and scattering processes.

  14. From blood coagulation to innate and adaptive immunity: the role of platelets in the physiology and pathology of autoimmune disorders.

    Science.gov (United States)

    Łukasik, Zuzanna Małgorzata; Makowski, Marcin; Makowska, Joanna Samanta

    2018-02-28

    Thrombosis and cardiovascular complications are common manifestations of a variety of pathological conditions, including infections and chronic inflammatory diseases. Hence, there is great interest in determining the hitherto unforeseen immune role of the main blood coagulation executor-the platelet. Platelets store and release a plethora of immunoactive molecules, generate microparticles, and interact with cells classically belonging to the immune system. The observed effects of platelet involvement in immune processes, especially in autoimmune diseases, are conflicting-from inciting inflammation to mediating its resolution. An in-depth understanding of the role of platelets in inflammation and immunity could open new therapeutic pathways for patients with autoimmune disorders. This review aims to summarize the current knowledge on the role of platelets in the patomechanisms of autoimmune disorders and suggests directions for future research.

  15. Influence of the centrifuge time of primary plasma tubes on routine coagulation testing.

    Science.gov (United States)

    Lippi, Giuseppe; Salvagno, Gian Luca; Montagnana, Martina; Manzato, Franco; Guidi, Gian Cesare

    2007-07-01

    Preparation of blood specimens is a major bottleneck in the laboratory throughput. Reliable strategies for reducing the time required for specimen processing without affecting quality should be acknowledged, especially for laboratories performing stat analyses. The present investigation was planned to establish a minimal suitable centrifuge time for primary samples collected for routine coagulation testing. Five sequential primary vacuum tubes containing 0.109 mol/l buffered trisodium citrate were collected from 10 volunteers and were immediately centrifuged on a conventional centrifuge at 1500 x g, at room temperature for 1, 2, 5, 10 and 15 min, respectively. Hematological and routine coagulation testing, including prothrombin time, activated partial thromboplastin time and fibrinogen, were performed. The centrifugation time was inversely associated with residual blood cell elements in plasma, especially platelets. Statistically significant variations from the reference 15-min centrifuge specimens were observed for fibrinogen in samples centrifuged for 5 min at most and for the activated partial thromboplastin time in samples centrifuged for 2 min at most. Meaningful biases related to the desirable bias were observed for fibrinogen in samples centrifuged for 2 min at most, and for the activated partial thromboplastin time in samples centrifuged for 1 min at most. According to our experimental conditions, a 5-10 min centrifuge time at 1500 x g may be suitable for primary tubes collected for routine coagulation testing.

  16. Breeding of transgenic cattle for human coagulation factor IX by a combination of lentiviral system and cloning.

    Science.gov (United States)

    Monzani, P S; Sangalli, J R; De Bem, T H C; Bressan, F F; Fantinato-Neto, P; Pimentel, J R V; Birgel-Junior, E H; Fontes, A M; Covas, D T; Meirelles, F V

    2013-02-28

    Recombinant coagulation factor IX must be produced in mammalian cells because FIX synthesis involves translational modifications. Human cell culture-based expression of human coagulation factor IX (hFIX) is expensive, and large-scale production capacity is limited. Transgenic animals may greatly increase the yield of therapeutic proteins and reduce costs. In this study, we used a lentiviral system to obtain transgenic cells and somatic cell nuclear transfer (SCNT) to produce transgenic animals. Lentiviral vectors carrying hFIX driven by 3 bovine β-casein promoters were constructed. Bovine epithelial mammary cells were transduced by lentivirus, selected with blasticidin, plated on extracellular matrix, and induced by lactogenic hormones; promoter activity was evaluated by quantitative PCR. Transcriptional activity of the 5.335-kb promoter was 6-fold higher than the 3.392- and 4.279-kb promoters, which did not significantly differ. Transgenic bovine fibroblasts were transduced with lentivirus carrying the 5.335-kb promoter and used as donor cells for SCNT. Cloned transgenic embryo production yielded development rates of 28.4%, similar to previous reports on cloned non-transgenic embryos. The embryos were transferred to recipient cows (N = 21) and 2 births of cloned transgenic cattle were obtained. These results suggest combination of the lentiviral system and cloning may be a good strategy for production of transgenic cattle.

  17. An Easy Method to Eliminate the Effect of Lupus Anticoagulants in the Coagulation Factor Assay.

    Science.gov (United States)

    Tang, Ning; Yin, Shiyu

    2016-07-01

    To build and evaluate intrinsic coagulation factor assays which can eliminate the effect of lupus anticoagulants (LAC). Commercial silica clotting time confirmatory (SCT-C) reagent containing sufficient synthetic phospholipid and routine activated partial thromboplastin time (APTT) reagent were each used for one-stage detection of FVIII, FIX, and FXI activities, in samples with or without LAC, and the results were compared. For samples without LAC, consistent results of FVIII, FIX, and FXI using both SCT-C reagent and APTT reagent were obtained. For samples with LAC, the assays with SCT-C reagent not only could eliminate the effect of strong lupus anticoagulants but also needed fewer dilutions than that with routine APTT reagent. The intrinsic factor detections by SCT-C reagent are credible and convenient to be used for samples with LAC.

  18. A close insight to factor VIII inhibitor in the congenital hemophilia A.

    Science.gov (United States)

    Tabriznia-Tabrizi, Shamsoreza; Gholampour, Marzie; Mansouritorghabeh, Hassan

    2016-09-01

    Hemophilia A (HA) has an X-linked pattern of inheritance and is the most common of the hemorrhagic disorders. HA is caused by a decreased or deficiency of the functional clotting factor VIII (FVIII) and effects 1 in 5000-10,000 male births. The common treatment for hemophilia is replacement therapy by plasma-derived or recombinant FVIII. Approximately 20-30% of people with a severe type of HA develop an inhibitor and this phenomenon is the main challenge in the management of these patients. Genetic factors and environmental determinants contribute to inhibitor development. Here, the roles of various genetic and environmental factors such as the type of FVIII concentrate used, the number of exposure days, and peak treatment time will be discussed in detail. It seems this information is helpful for hematologists. A literature review was done in January 2016 on PubMed and Scopus using the following keywords:' h(a)emophilia A & factor VIII inhibitor', 'h(a)emophilia A & factor VIII alloantibody', 'h(a)emophilia A & inhibitor'. There was no time limitation; however, there was an English language limitation placed on the articles selected. Expert commentary: Influential genetic and environmental factors in developing inhibitors have been discussed. Most of the risk factors are related to previously untreated patients with hemophili.

  19. Effects of coagulation temperature on measurements of complement function in serum samples from patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Baatrup, G; Sturfelt, G; Junker, A

    1992-01-01

    Blood samples from 15 patients with systemic lupus erythematosus (SLE) and 15 healthy blood donors were allowed to coagulate for one hour at room temperature, followed by one hour at 4 or 37 degrees C. The complement activity of the serum samples was assessed by three different functional assays...

  20. Quality of Clotting Factor Activity in Fresh Frozen Plasma at Thaw with a Microwave System and after Storage at 4 degrees C for 48 Hours.

    Science.gov (United States)

    Kuta, Piotr; Hauck-Dlimi, Barbara; Strobel, Julian; Zimmermann, Robert; Eckstein, Reinhold

    2016-01-01

    Uncontrolled hemorrhage in polytrauma patients usually results in rapid need of blood products. Despite the shorter thawing times of microwave devices for heating fresh frozen plasma (FFP), their use has remained controversial, and just a few laboratory analyses have been published on this topic. The aim of this study was to analyse the quality of clotting factors immediately after thawing FFP with a microwave device and after 48-hour post thaw storage at 4 degrees C. 24 FFP units of all four ABO blood groups (six of each blood group) were thawed with a Transfusio-therm 2000 and later stored at 4 degrees C for 48 hours. Samples were drawn aseptically and investigated on various clotting factors and protein proteases (fibrinogen, antithrombin, FII, FV, FVII, FVIII, FIX, FX, FXI, FXIII, vWF antigen and activity, protein S, and protein C) using standard coagulation and chromogenic assays immediately after thawing and again after a 48-hour storage period at 4 degrees C. All units were tested for both anaerobic and aerobic microbial contamination using standard operating procedures immediately after thawing. After thawing, all coagulation factors and protein protease activities were within normal ranges. Blood group O individuals had approximately 25% lower plasma levels of vWF antigen and activity. After a 48-hour storage period at 4 degrees C, FVIII and FIX activities declined significantly in all blood groups, whereas the remaining clotting factors remained comparably stable. Immediately after rapid thawing using a microwave system, all FFP units contained adequate coagulation factor activities to maintain hemostatic activity at the time of product thaw. The post thaw refrigerated storage caused an anticipated decrease in factor VIII and IX activities, but retained normal coagulation factor levels of many plasma proteins. Therefore we conclude that the Transfusio-therm 2000 has no clinically significant influence on the activity of clotting factors and plasma

  1. Selective kallikrein inhibitors alter human neutrophil elastase release during extracorporeal circulation

    NARCIS (Netherlands)

    Wachtfogel, Y.T.; Hack, C.E.; Nuijens, J.H; Kettner, C.; Reilly, T.M.; Knabb, R.M.; Bischoff, Rainer; Tschesche, H.; Wenzel, H.; Kucich, U.

    1995-01-01

    Cardiopulmonary bypass causes hemorrhagic complications and initiates a biochemical and cellular "whole body inflammatory response." This study investigates whether a variety of selective inhibitors of the contact pathway of intrinsic coagulation modulate complement and neutrophil activation during

  2. Avaliação de anticoagulantes naturais e de fatores da coagulação em pacientes com distúrbios congênitos de glicosilação (DCG tipo I An evaluation of natural anticoagulants and coagulation factors in patients with congenital disorders of glycosylation type I

    Directory of Open Access Journals (Sweden)

    Anna Letícia Soares

    2010-01-01

    with neurologic symptoms that include psychomotor retardation, ataxia, hypotonia and stroke-like episodes. Many haemostatic system proteins only present biological activity after glycosylation. The aim of this study was to evaluate coagulation inhibitors (free protein S, protein C and antithrombin and coagulation factors (VIII, IX and XI in CDG type I patients. Eleven patients with CDG type I (three males and eight females with a mean age of 5.6 years old, and eight patients without CDG (four males and four females with a mean age of 4.5 years old (control group were evaluated. The diagnoses of CDG type I were confirmed by isoelectric focusing of serum transferrin. When coagulation inhibitors were evaluated, decreased activity of free protein S and protein C, and a pronounced reduction of antithrombin were observed compared to the control group. There was no significant difference for coagulation factors VIII and IX but a markedly decrease in factor XI. The present results suggest that a combined deficiency of coagulation inhibitors is responsible for the pro-thrombotic state observed in CDG patients. We recommend that a haemostatic analysis should be performed in CDG patients with clinical haemostatic manifestations before invasive procedures are performed.

  3. Removal Natural Organic Matter (NOM in Peat Water from Wetland Area by Coagulation-Ultrafiltration Hybrid Process with Pretreatment Two-Stage Coagulation

    Directory of Open Access Journals (Sweden)

    Mahmud Mahmud

    2016-06-01

    Full Text Available The primary problem encountered in the application of membrane technology was membrane fouling. During this time, hybrid process by coagulation-ultrafiltration in drinking water treatment that has been conducted by some research, using by one-stage coagulation. The goal of this research was to investigate the effect of two-stage coagulation as a pretreatment towards performance of the coagulation-ultrafiltration hybrid process for removal NOM in the peat water. Coagulation process, either with the one-stage or two-stage coagulation was very good in removing charge hydrophilic fraction, i.e. more than 98%. NOM fractions of the peat water, from the most easily removed by the two-stage coagulation and one-stage coagulation process was charged hydrophilic>strongly hydrophobic>weakly hydrophobic>neutral hydrophilic. The two-stage coagulation process could removed UV254 and colors with a little better than the one-stage coagulation at the optimum coagulant dose. Neutral hydrophilic fraction of peat water NOM was the most influential fraction of UF membrane fouling. The two-stage coagulation process better in removing the neutral hidrophilic fraction, while removing of the charged hydrophilic, strongly hydrophobic and weakly hydrophobic similar to the one-stage coagulation. Hybrid process by pretreatment with two-stage coagulation, beside can increased removal efficiency of UV254 and color, also can reduced fouling rate of the ultrafiltration membraneIt must not exceed 250 words, contains a brief summary of the text, covering the whole manuscript without being too elaborate on every section. Avoid any abbreviation, unless it is a common knowledge or has been previously stated.

  4. Removal Natural Organic Matter (NOM in Peat Water from Wetland Area by Coagulation-Ultrafiltration Hybrid Process with Pretreatment Two-Stage Coagulation

    Directory of Open Access Journals (Sweden)

    Mahmud Mahmud

    2013-11-01

    Full Text Available The primary problem encountered in the application of membrane technology was membrane fouling. During this time, hybrid process by coagulation-ultrafiltration in drinking water treatment that has been conducted by some research, using by one-stage coagulation. The goal of this research was to investigate the effect of two-stage coagulation as a pretreatment towards performance of the coagulation-ultrafiltration hybrid process for removal NOM in the peat water. Coagulation process, either with the one-stage or two-stage coagulation was very good in removing charge hydrophilic fraction, i.e. more than 98%. NOM fractions of the peat water, from the most easily removed by the two-stage coagulation and one-stage coagulation process was charged hydrophilic>strongly hydrophobic>weakly hydrophobic>neutral hydrophilic. The two-stage coagulation process could removed UV254 and colors with a little better than the one-stage coagulation at the optimum coagulant dose. Neutral hydrophilic fraction of peat water NOM was the most influential fraction of UF membrane fouling. The two-stage coagulation process better in removing the neutral hidrophilic fraction, while removing of the charged hydrophilic, strongly hydrophobic and weakly hydrophobic similar to the one-stage coagulation. Hybrid process by pretreatment with two-stage coagulation, beside can increased removal efficiency of UV254 and color, also can reduced fouling rate of the ultrafiltration membraneIt must not exceed 250 words, contains a brief summary of the text, covering the whole manuscript without being too elaborate on every section. Avoid any abbreviation, unless it is a common knowledge or has been previously stated.

  5. The Story of Serum Prothrombin Conversion Accelerator, Proconvertin, Stable Factor, Cothromboplastin, Prothrombin Accelerator or Autoprothrombin I, and Their Subsequent Merging into Factor VII.

    Science.gov (United States)

    Girolami, Antonio; Cosi, Elisabetta; Santarossa, Claudia; Ferrari, Silvia; Luigia Randi, Maria

    2015-06-01

    Factor VII (FVII) deficiency is one of the two congenital coagulation disorders that was not discovered by the description of a new bleeding patient whose clotting pattern did not fit the blood coagulation knowledge of the time (the other is factor XIII deficiency). The existence of an additional factor capable of accelerating the conversion of prothrombin into thrombin was suspected before 1951, the year in which the first family with FVII deficiency was discovered. As several investigators were involved in the discovery of FVII deficiency from both sides of the Atlantic, several different names were tentatively suggested to define this entity, namely stable factor (in contrast with labile factor or FV), cothromboplastin, proconvertin, serum prothrombin conversion accelerator, prothrombin acceleration, and autoprothrombin I. The last term was proposed by those who denied the existence of this new entity, which was instead considered to be a derivate of prothrombin activation, namely autoprothrombin. The description of several families, from all over the world, of the same defect, however clearly demonstrated the singularity of the condition. Factor VII was then proposed to define this protein. In subsequent years, several variants were described with peculiar reactivity toward tissue thromboplastins of different origin. Molecular biology techniques demonstrated several gene mutations, usually missense mutations, often involving exon 8 of the FVII gene. Later studies dealt with the relation of FVII with tissue factor and activated FVII (FVIIa). The evaluation of circulating FVIIa was made possible by the use of a truncated form of tissue factor, which is only sensitive to FVIIa present in the circulation. The development of FVII concentrates, both plasma derived and recombinant, has facilitated therapeutic management of FVII-deficient patients. The use of FVIIa concentrates was noted to be associated with the occasional occurrence of thrombotic events, mainly

  6. Phosphodiesterase inhibitors enhance object memory independent of cerebral blood flow and glucose utilization in rats.

    Science.gov (United States)

    Rutten, Kris; Van Donkelaar, Eva L; Ferrington, Linda; Blokland, Arjan; Bollen, Eva; Steinbusch, Harry Wm; Kelly, Paul At; Prickaerts, Jos Hhj

    2009-07-01

    Phosphodiesterase (PDE) inhibitors prevent the breakdown of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), and are currently studied as possible targets for cognitive enhancement. Earlier studies indicated beneficial effects of PDE inhibitors in object recognition. In this study we tested the effects of three PDE inhibitors on spatial memory as assessed in a place and object recognition task. Furthermore, as both cAMP and cGMP are known vasodilators, the effects of PDE inhibition on cognitive functions could be explained by enhancement of cerebrovascular function. We examined this possibility by measuring the effects of PDE5 and PDE4 inhibitor treatment on local cerebral blood flow and glucose utilization in rats using [14C]-iodoantipyrine and [14C]-2-deoxyglucose quantitative autoradiography, respectively. In the spatial location task, PDE5 inhibition (cGMP) with vardenafil enhanced only early phase consolidation, PDE4 inhibition (cAMP) with rolipram enhanced only late phase consolidation, and PDE2 inhibition (cAMP and cGMP) with Bay 60-7550 enhanced both consolidation processes. Furthermore, PDE5 inhibition had no cerebrovascular effects in hippocampal or rhinal areas. PDE4 inhibition increased rhinal, but not hippocampal blood flow, whereas it decreased glucose utilization in both areas. In general, PDE5 inhibition decreased the ratio between blood flow and glucose utilization, indicative of general oligaemia; whereas PDE4 inhibition increased this ratio, indicative of general hyperemia. Both oligaemic and hyperemic conditions are detrimental for brain function and do not explain memory enhancement. These results underscore the specific effects of cAMP and cGMP on memory consolidation (object and spatial memory) and provide evidence that the underlying mechanisms of PDE inhibition on cognition are independent of cerebrovascular effects.

  7. PILOT PLANT STUDY ON NATURAL WATER COAGULANTS AS COAGULAN AIDS FOR WATER SUPPLY

    Directory of Open Access Journals (Sweden)

    B BINA

    2001-06-01

    Full Text Available Introduction: Natural plant coagulants have an important role to play in provision of portable water to rural communities in the developing world. The plant material that their coagulation properties have been confirmed in previous lab scale studies and can be found widely in Iran was selected as coagulant aids. Pilot plant study was done to evaluate the efficiency of natural material such as Starch/Gum Tragacanth, Fenugreek and Yeast as coagulant aids in conjunction with comercial alum. Methods: The pilot was placed in Isfahan Water Treatment Plant (IWTP and efficiency of these materials in removal of turbidity from raw water enters the IWTP was evaluated. The results indicated while these materials were used as coagulant aids in concentration of 1-5 mg/l conjunction with alum are able to reduced the turbidity and final residuals turbidity meets the standards limits. Results: The coagulation efficiency of these material were found to be effected by certain physico-chemical factors, namely, concentration of suspended solids, divalent cation metal and time of agitation. The relative importance of these variable was evaluated. The results of COD test proved that the natural coagulant aids in the optimum doses produce no any significant organic residual. Discussion: Economical considerations showed that using of these material as coagulant aids can cause reduction in alum consumption and in some cases are more econmical than synthetic polyelectrolyte.

  8. Inhibitors

    Science.gov (United States)

    ... JM, and the Hemophilia Inhibitor Research Study Investigators. Validation of Nijmegen-Bethesda assay modifications to allow inhibitor ... webinars on blood disorders Language: English (US) Español (Spanish) File Formats Help: How do I view different ...

  9. Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation

    DEFF Research Database (Denmark)

    Undén, Johan; Strandberg, Karin; Malm, Jan

    2009-01-01

    INTRODUCTION: A simple and accurate method of differentiating ischemic stroke and intracerebral hemorrhage (ICH) is potentially useful to facilitate acute therapeutic management. Blood measurements of biomarkers of brain damage and activation of the coagulation system may potentially serve as nov...

  10. Non-fasting factor VII coagulant activity (FVII:C) increased by high-fat diet

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Marckmann, P; Sandström, B

    1994-01-01

    :Bt/FVII:Am (a measure of FVII activation) increased from fasting levels on both diets, but most markedly on the high-fat diet. In contrast, FVII:Am (a measure of FVII protein) tended to decrease from fasting levels on both diets. FVII:C rose from fasting levels on the high-fat diet, but not on the low-fat diet....... The findings suggest that high-fat diets increase non-fasting FVII:C, and consequently may be associated with increased risk of thrombosis. Udgivelsesdato: 1994-Jun......Preliminary observations have suggested that non-fasting factor VII coagulant activity (FVII:C) may be related to the dietary fat content. To confirm this, we performed a randomised cross-over study. Seventeen young volunteers were served 2 controlled isoenergetic diets differing in fat content (20...

  11. Phase 1 Study of the E-Selectin Inhibitor GMI 1070 in Patients with Sickle Cell Anemia

    Science.gov (United States)

    Wun, Ted; Styles, Lori; DeCastro, Laura; Telen, Marilyn J.; Kuypers, Frans; Cheung, Anthony; Kramer, William; Flanner, Henry; Rhee, Seungshin; Magnani, John L.; Thackray, Helen

    2014-01-01

    Background Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease. Methods We performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions. Results The drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied. Conclusions GMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM), leukocyte activation (MAC-1, LFA-1, PM aggregates) and the coagulation cascade (tissue factor, thrombin-antithrombin complexes). Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing. Trial Registration ClinicalTrials.gov NCT00911495 PMID:24988449

  12. Phase 1 study of the E-selectin inhibitor GMI 1070 in patients with sickle cell anemia.

    Directory of Open Access Journals (Sweden)

    Ted Wun

    Full Text Available Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease.We performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions.The drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied.GMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM, leukocyte activation (MAC-1, LFA-1, PM aggregates and the coagulation cascade (tissue factor, thrombin-antithrombin complexes. Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing.ClinicalTrials.gov NCT00911495.

  13. Phase 1 study of the E-selectin inhibitor GMI 1070 in patients with sickle cell anemia.

    Science.gov (United States)

    Wun, Ted; Styles, Lori; DeCastro, Laura; Telen, Marilyn J; Kuypers, Frans; Cheung, Anthony; Kramer, William; Flanner, Henry; Rhee, Seungshin; Magnani, John L; Thackray, Helen

    2014-01-01

    Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease. We performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions. The drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied. GMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM), leukocyte activation (MAC-1, LFA-1, PM aggregates) and the coagulation cascade (tissue factor, thrombin-antithrombin complexes). Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing. ClinicalTrials.gov NCT00911495.

  14. Commonly Used Dietary Supplements on Coagulation Function during Surgery

    Directory of Open Access Journals (Sweden)

    Chong-Zhi Wang

    2015-07-01

    Full Text Available Background: Patients who undergo surgery appear to use dietary supplements significantly more frequently than the general population. Because they contain pharmacologically active compounds, dietary supplements may affect coagulation and platelet function during the perioperative period through direct effects, pharmacodynamic interactions, and pharmacokinetic interactions. However, in this regard, limited studies have been conducted that address the pharmacological interactions of dietary supplements. To avoid possible bleeding risks during surgery, information about the potential complications of dietary supplements during perioperative management is important for physicians. Methods: Through a systematic database search of all available years, articles were identified in this review if they included dietary supplements and coagulation/platelet function, while special attention was paid to studies published after 1990. Results: Safety concerns are reported in commercially available dietary supplements. Effects of the most commonly used natural products on blood coagulation and platelet function are systematically reviewed, including 11 herbal medicines (echinacea, ephedra, garlic, ginger, ginkgo, ginseng, green tea, kava, saw palmetto, St John’s wort, and valerian and four other dietary supplements (coenzyme Q10, glucosamine and chondroitin sulfate, fish oil, and vitamins. Bleeding risks of garlic, ginkgo, ginseng, green tea, saw palmetto, St John’s wort, and fish oil are reported. Cardiovascular instability was observed with ephedra, ginseng, and kava. Pharmacodynamic and pharmacokinetic interactions between dietary supplements and drugs used in the perioperative period are discussed. Conclusions: To prevent potential problems associated with the use of dietary supplements, physicians should be familiar with the perioperative effects of commonly used dietary supplements. Since the effects of dietary supplements on coagulation and platelet

  15. Commonly Used Dietary Supplements on Coagulation Function during Surgery

    Science.gov (United States)

    Wang, Chong-Zhi; Moss, Jonathan; Yuan, Chun-Su

    2015-01-01

    Abstract Background Patients who undergo surgery appear to use dietary supplements significantly more frequently than the general population. Because they contain pharmacologically active compounds, dietary supplements may affect coagulation and platelet function during the perioperative period through direct effects, pharmacodynamic interactions, and pharmacokinetic interactions. However, in this regard, limited studies have been conducted that address the pharmacological interactions of dietary supplements. To avoid possible bleeding risks during surgery, information about the potential complications of dietary supplements during perioperative management is important for physicians. Methods Through a systematic database search of all available years, articles were identified in this review if they included dietary supplements and coagulation/platelet function, while special attention was paid to studies published after 1990. Results Safety concerns are reported in commercially available dietary supplements. Effects of the most commonly used natural products on blood coagulation and platelet function are systematically reviewed, including 11 herbal medicines (echinacea, ephedra, garlic, ginger, ginkgo, ginseng, green tea, kava, saw palmetto, St John’s wort, and valerian) and four other dietary supplements (coenzyme Q10, glucosamine and chondroitin sulfate, fish oil, and vitamins). Bleeding risks of garlic, ginkgo, ginseng, green tea, saw palmetto, St John’s wort, and fish oil are reported. Cardiovascular instability was observed with ephedra, ginseng, and kava. Pharmacodynamic and pharmacokinetic interactions between dietary supplements and drugs used in the perioperative period are discussed. Conclusions To prevent potential problems associated with the use of dietary supplements, physicians should be familiar with the perioperative effects of commonly used dietary supplements. Since the effects of dietary supplements on coagulation and platelet function are

  16. Commonly Used Dietary Supplements on Coagulation Function during Surgery.

    Science.gov (United States)

    Wang, Chong-Zhi; Moss, Jonathan; Yuan, Chun-Su

    2015-09-01

    Patients who undergo surgery appear to use dietary supplements significantly more frequently than the general population. Because they contain pharmacologically active compounds, dietary supplements may affect coagulation and platelet function during the perioperative period through direct effects, pharmacodynamic interactions, and pharmacokinetic interactions. However, in this regard, limited studies have been conducted that address the pharmacological interactions of dietary supplements. To avoid possible bleeding risks during surgery, information of potential complications of dietary supplements during perioperative management is important for physicians. Through a systematic database search of all available years, articles were identified in this review if they included dietary supplements and coagulation/platelet function, while special attention was paid to studies published after 1990. Safety concerns are reported in commercially available dietary supplements. Effects of the most commonly used natural products on blood coagulation and platelet function are systematically reviewed, including 11 herbal medicines (echinacea, ephedra, garlic, ginger, ginkgo, ginseng, green tea, kava, saw palmetto, St John's wort, and valerian) and 4 other dietary supplements (coenzyme Q 10 , glucosamine and chondroitin sulfate, fish oil, and vitamins). Bleeding risks of garlic, ginkgo, ginseng, green tea, saw palmetto, St John's wort, and fish oil are reported. Cardiovascular instability was observed with ephedra, ginseng, and kava. Pharmacodynamic and pharmacokinetic interactions between dietary supplements and drugs used in the perioperative period are discussed. To prevent potential problems associated with the use of dietary supplements, physicians should be familiar with the perioperative effects of commonly used dietary supplements. Since the effects of dietary supplements on coagulation and platelet function are difficult to predict, it is prudent to advise their

  17. The effects of transport by car on coagulation tests.

    Science.gov (United States)

    Ergin, Merve; Erdogan, Serpil; Akturk, Onur; Erel, Ozcan

    2017-10-26

    This research investigated the effects of the transport of blood samples between centers/laboratories by car on coagulation tests. Five tubes of blood samples were taken from 20 healthy volunteers. The samples consisted of a baseline (control) group, centrifuged and noncentrifuged transported samples; centrifuged and noncentrifuged untransported samples. The groups of centrifuged and noncentrifuged samples were transported by car for 2 h. The centrifuged and noncentrifuged untransported samples were incubated in the laboratory until the transported samples arrived. Prothrombin time (PT) and activated partial thromboplastin time (APTT) tests were conducted for all samples. Significant differences between the baseline group and the centrifuged and noncentrifuged transported samples and the noncentrifuged untransported samples were found for APTT levels (pcar.

  18. Polyphenol Compound as a Transcription Factor Inhibitor

    Directory of Open Access Journals (Sweden)

    Seyeon Park

    2015-10-01

    Full Text Available A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor–DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein–protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1, c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and β-catenin/T cell factor (Tcf.

  19. Intraventricular haemorrhage in preterm infants--can we improve outcome by addressing coagulation?

    Science.gov (United States)

    Kuperman, Amir A; Brenner, Benjamin; Kenet, Gili

    2015-11-01

    During the last few decades, the survival of preterm infants has increased dramatically. Nevertheless, with the increasing number of very young and extremely low birth weight infants, morbidity is still a major problem. Intraventricular Haemorrhage (IVH) is a major complication of preterm birth, and large haemorrhages or haemorrhages associated with parenchymal brain lesions may yield a high rate of future disability. IVH is a complex, multi-factorial disorder. Prematurity and low birth weight remain as its most important risk factors, affecting vulnerability of the germinal matrix as well as the coagulation system. Approximately 80% of IVHs occur by 72 h after birth, but a considerable proportion of IVH is already visible on the first cranial ultrasound scan within a few hours of birth. The hypothesis that a severe coagulation deficiency in the premature newborn could be a major contributing factor to IVH has been suggested, and small open label interventional studies targeting the premature coagulation system have been conducted with ethamsylate, vitamin K, fresh frozen plasma, recombinant activated factor VII and prothrombin complex concentrate. The outcome of these studies will be reviewed.

  20. Investigational drugs for coagulation disorders.

    Science.gov (United States)

    Mannucci, Pier Mannuccio; Mancuso, Maria Elisa

    2013-08-01

    The current standard treatment in persons with hemophilia (PWH) is prophylaxis, given intravenously twice or thrice weekly, which is associated with a non negligible burden on patients' quality of life. Therefore the main attempts aiming to improve the management of PWH are targeted towards the development of a new generation of coagulation factors endowed with properties facilitating prophylaxis and/or a better control of bleeding. This article summarizes the main results obtained so far in the development of new antihemophilic products, and emphasizes the formidable requirements imposed upon by regulatory agencies to get marketing authorization for new drugs, which make progress in this field difficult. Published literature on new molecules for replacement treatment in hemophilia A and B has been retrieved by using PubMed search and all ongoing clinical trials have been looked for online. New molecules are usually engineered to have a longer plasma half-life but also in some instances a higher potency. The prolongation of half-life may be obtained by using sustained release delivery vehicles, by chemical modification or by creating fusion proteins. Factors VIII, IX and VII have been variably modified in order to obtain improved coagulation products and results from Phase I/II studies are encouraging, particularly for factor IX. However, Phase III studies that should provide evidence on efficacy and effectiveness more cogent for clinical use are still ongoing and results are not yet available.

  1. TRAITEMENT DES EAUX USEES PAR COAGULATION-FLOCULATION EN UTILISANT LE SULFATE D’ALUMINIUM COMME COAGULANT

    Directory of Open Access Journals (Sweden)

    Nora SEGHAIRI

    2017-12-01

    Full Text Available Domestic wastewater treatment by coagulation-flocculation is widely used internationally. This treatment reduces color and turbidity, indicating organic and inorganic contaminants, but at acceptable levels for treated waste water discharged into the receiving environment. The objective of this study is to optimize the treatment of wastewater by coagulation-flocculation using aluminum sulphate as a coagulant. Various reaction parameters are taken into account, such as the coagulant dose, the pH of the solutions, the conductivity, the BOD5, the nitrates, the ammonium and the phosphates. We found from the different results obtained the optimal dose of aluminum sulphate is 400 mg/l with a reduction of 96.31%, 82.44% 90.95% and 78.74% respectively for phosphates, nitrates, ammonium and BOD5. It is recognized that pH influences the abatement rates of pollution contained in wastewater. For each water, there is a pH range for which coagulation- flocculation takes place rapidly. For our study, the optimum pH for removal of BOD5 and ammonium is between 6 and 7.

  2. Population pharmacokinetics of recombinant coagulation factor VIII-SingleChain in patients with severe hemophilia A.

    Science.gov (United States)

    Zhang, Y; Roberts, J; Tortorici, M; Veldman, A; St Ledger, K; Feussner, A; Sidhu, J

    2017-06-01

    Essentials rVIII-SingleChain is a unique recombinant factor VIII (FVIII) molecule. A population pharmacokinetic model was based on FVIII activity of severe hemophilia A patients. The model was used to simulate factor VIII activity-time profiles for various dosing scenarios. The model supports prolonged dosing of rVIII-SingleChain with intervals of up to twice per week. Background Single-chain recombinant coagulation factor VIII (rVIII-SingleChain) is a unique recombinant coagulation factor VIII molecule. Objectives To: (i) characterize the population pharmacokinetics (PK) of rVIII-SingleChain in patients with severe hemophilia A; (ii) identify correlates of variability in rVIII-SingleChain PK; and (iii) simulate various dosing scenarios of rVIII-SingleChain. Patients/Methods A population PK model was developed, based on FVIII activity levels of 130 patients with severe hemophilia A (n = 91 for ≥ 12-65 years; n = 39 for  85% and > 93% of patients were predicted to maintain FVIII activity level above 1 IU dL -1 , at all times with three-times-weekly dosing (given on days 0, 2, and 4.5) at the lowest (20 IU kg -1 ) and highest (50 IU kg -1 ) doses, respectively. For twice weekly dosing (days 0 and 3.5) of 50 IU kg -1 rVIII-SingleChain, 62-80% of patients across all ages were predicted to maintain a FVIII activity level above 1 IU dL -1 at day 7. Conclusions The population PK model adequately characterized rVIII-SingleChain PK, and the model can be utilized to simulate FVIII activity-time profiles for various dosing scenarios. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

  3. A case of radiation hemorrhagic gastritis successfully treated by endoscopic argon plasma coagulation

    International Nuclear Information System (INIS)

    Furukawa, Koichi; Ho, Nichyau; Kuroda, Ken; Ikarashi, Kentarou; Hata, Koujirou; Tukioka, Satosi

    2003-01-01

    A 72-year-old woman underwent irradiation of 46 Grey in total dose, for lumbago of the advanced pancreatic cancer in August 2000. She was admitted to our hospital due to severe anemia in February 2001 with occasionally positive fecal occult blood. Endoscopy revealed erosive gastric mucosa diffuse in the lower body of the stomach, which resulted from radiation. We applied argon plasma coagulation (APC) in March 2001 and succeeded in hemostasis of the widely spreading radiation hemorrhagic gastritis. The progress of the severe anemia improved without cicatricial stenosis. As the coagulation of the APC is limited in the surface mucosa, APC is an easy and effective treatment for radiation hemorrhagic gastritis. (author)

  4. Inhibitor development after liver transplantation in congenital factor VII deficiency.

    Science.gov (United States)

    See, W-S Q; Chang, K-O; Cheuk, D K-L; Leung, Y-Y R; Chan, G C-F; Chan, S-C; Ha, S-Y

    2016-09-01

    Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement. © 2016 John Wiley & Sons Ltd.

  5. Microwave tissue coagulation: effects of power and treatment time on coagulation size

    International Nuclear Information System (INIS)

    Kang, Seung Pyung; Kim, Young Hwan; Park, Dong Man; Kim, Jeong Seok; Park, Seo Young; Cha, Soon Joo; Hur, Gham

    1999-01-01

    To determine the effects of power and coagulation time on lesion size of ex-vivo bovine liver using microwaves. Six bovine livers were divided into two groups (first group : 30W output, second group : 60W output) and microwave coagulation was performed for 30, 60, and 120 sec. Thermal injury site was then observed by means of sonography, and the maximal transverse diameter of the echo-change portion after microwave coagulation was measured. On the section of specimen, maximal transverse diameters of the thermal injury site were measured by gross inspection and compared with the result of sonographic measurement. Maximal transverse diameters of hyperechoic lesions of the first group, as seen on sonography, were 8.3mm, 12.2mm, and 15.6mm, and the maximal transverse diameters of thermal injury sites on gross specimens were 9.1mm, 12.0mm, and 15.1mm, respectively. Maximal transverse diameters of hyperechoic lesions of the second group, as seen on sonography, were 12.1mm, 17.4mm, and 21.2mm and maximal transverse diameters of thermal injury sites on gross specimens were 13.2mm, 16.0mm, and 20.0mm, respectively. Statistically maximal transverse diameters of hyperechoic lesions, as seen on sonography, correlated closely with the gross findings of maximal transverse diameters of thermal injury sites (P < .05). Maximal transverse diameters of thermal injury sites were significantly increased as the output of the microwave coagulator and the duration of coagulation time increased (P < .05)

  6. Phospholipid Binding Protein C Inhibitor (PCI) Is Present on Microparticles Generated In Vitro and In Vivo

    Science.gov (United States)

    Einfinger, Katrin; Badrnya, Sigrun; Furtmüller, Margareta; Handschuh, Daniela; Lindner, Herbert; Geiger, Margarethe

    2015-01-01

    Protein C inhibitor is a secreted, non-specific serine protease inhibitor with broad protease reactivity. It binds glycosaminoglycans and anionic phospholipids, which can modulate its activity. Anionic phospholipids, such as phosphatidylserine are normally localized to the inner leaflet of the plasma membrane, but are exposed on activated and apoptotic cells and on plasma membrane-derived microparticles. In this report we show by flow cytometry that microparticles derived from cultured cells and activated platelets incorporated protein C inhibitor during membrane blebbing. Moreover, protein C inhibitor is present in/on microparticles circulating in normal human plasma as judged from Western blots, ELISAs, flow cytometry, and mass spectrometry. These plasma microparticles are mainly derived from megakaryocytes. They seem to be saturated with protein C inhibitor, since they do not bind added fluorescence-labeled protein C inhibitor. Heparin partially removed microparticle-bound protein C inhibitor, supporting our assumption that protein C inhibitor is bound via phospholipids. To assess the biological role of microparticle-bound protein C inhibitor we performed protease inhibition assays and co-precipitated putative binding partners on microparticles with anti-protein C inhibitor IgG. As judged from amidolytic assays microparticle-bound protein C inhibitor did not inhibit activated protein C or thrombin, nor did microparticles modulate the activity of exogenous protein C inhibitor. Among the proteins co-precipitating with protein C inhibitor, complement factors, especially complement factor 3, were most striking. Taken together, our data do not support a major role of microparticle-associated protein C inhibitor in coagulation, but rather suggest an interaction with proteins of the complement system present on these phospholipid vesicles. PMID:26580551

  7. Tulathromycin disturbs blood oxidative and coagulation status | Er ...

    African Journals Online (AJOL)

    ... (white and red blood cells) and arterial blood gas parameters (packed cell volume, ... excess in vitro, oxygen saturation, sodium and potassium) were also determined. Tulathromycin increased (P < 0.05) the levels of malondialdehyde, nitric ...

  8. Two-factor logistic regression in pediatric liver transplantation

    Science.gov (United States)

    Uzunova, Yordanka; Prodanova, Krasimira; Spasov, Lyubomir

    2017-12-01

    Using a two-factor logistic regression analysis an estimate is derived for the probability of absence of infections in the early postoperative period after pediatric liver transplantation. The influence of both the bilirubin level and the international normalized ratio of prothrombin time of blood coagulation at the 5th postoperative day is studied.

  9. The coagulation factor Xa/protease activated receptor-2 axis in the progression of liver fibrosis : a multifaceted paradigm

    NARCIS (Netherlands)

    Borensztajn, Keren; von der Thusen, Jan H.; Peppelenbosch, Maikel P.; Spek, C. Arnold

    2010-01-01

    Introduction Activation of the coagulation cascade during liver fibrosis: a puzzling paradox Protease-activated receptors: the link between coagulation cascade activation and liver fibrosis Expression and distribution of human PAR-2 in normal and pathological liver tissue FXa signalling on PAR-2

  10. Emergent self-similarity of cluster coagulation

    Science.gov (United States)

    Pushkin, Dmtiri O.

    A wide variety of nonequilibrium processes, such as coagulation of colloidal particles, aggregation of bacteria into colonies, coalescence of rain drops, bond formation between polymerization sites, and formation of planetesimals, fall under the rubric of cluster coagulation. We predict emergence of self-similar behavior in such systems when they are 'forced' by an external source of the smallest particles. The corresponding self-similar coagulation spectra prove to be power laws. Starting from the classical Smoluchowski coagulation equation, we identify the conditions required for emergence of self-similarity and show that the power-law exponent value for a particular coagulation mechanism depends on the homogeneity index of the corresponding coagulation kernel only. Next, we consider the current wave of mergers of large American banks as an 'unorthodox' application of coagulation theory. We predict that the bank size distribution has propensity to become a power law, and verify our prediction in a statistical study of the available economical data. We conclude this chapter by discussing economically significant phenomenon of capital condensation and predicting emergence of power-law distributions in other economical and social data. Finally, we turn to apparent semblance between cluster coagulation and turbulence and conclude that it is not accidental: both of these processes are instances of nonlinear cascades. This class of processes also includes river network formation models, certain force-chain models in granular mechanics, fragmentation due to collisional cascades, percolation, and growing random networks. We characterize a particular cascade by three indicies and show that the resulting power-law spectrum exponent depends on the indicies values only. The ensuing algebraic formula is remarkable for its simplicity.

  11. Coagulation Status in Hidradenitis Suppurativa

    DEFF Research Database (Denmark)

    Miller, Iben Marie; Johansen, Maria Egede; Mogensen, Ulla B

    2015-01-01

    BACKGROUND: Chronic inflammatory diseases other than hidradenitis suppurativa (HS) have been associated with prothrombotic/hypercoagulable status. OBJECTIVE: To investigate a possible association between the chronic inflammatory skin disease HS and prothrombotic/hypercoagulable state. METHODS: We.......3432). CONCLUSION: We did not find an association between HS and prothrombotic/hypercoagulable status. Thus, thrombocytes may not be activated in HS. Furthermore, INR may not be affected in HS, suggesting that intrinsic and vitamin K-dependent coagulation factors appear unaffected....

  12. Characterization of core/shell Cu/Ag nanopowders synthesized by electrochemistry and assessment of their impact on hemolysis, platelet aggregation, and coagulation on human blood for potential wound dressing use

    Science.gov (United States)

    Laloy, Julie; Haguet, Hélène; Alpan, Lutfiye; Mancier, Valérie; Mejia, Jorge; Levi, Samuel; Dogné, Jean-Michel; Lucas, Stéphane; Rousse, Céline; Fricoteaux, Patrick

    2017-08-01

    Copper/silver core/shell nanopowders with different metal ratio have been elaborated by electrochemistry (ultrasound-assisted electrolysis followed by a displacement reaction). Characterization was performed by several methods (X-ray diffraction, scanning electron microscope, energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, centrifugal liquid sedimentation, and zeta potential measurements). The mean diameter of all nanoparticles is around 10 nm. The impact of each nanopowder on hemolysis, platelet aggregation, and coagulation has been studied on whole human blood. Hemolysis assays were performed with spectrophotometric measurement and platelet aggregation, with light transmission aggregometry and was compared to Cu/Pt core/shell nanoparticles with similar size as negative control. Calibrated thrombin generation test has been used for a coagulation study. They neither impact platelet aggregation nor hemolysis and have a procoagulant effect whatever their composition (i.e., metal ratio). These results highlight that such nanopowders have a potential use in medical applications (e.g., wound dressing).

  13. Pulsed electric field extraction enhanced anti-coagulant effect of fungal polysaccharide from Jew's ear (Auricularia auricula).

    Science.gov (United States)

    Li, Changtian; Mao, Xinxin; Xu, Baojun

    2013-01-01

    As a Chinese herbal medicine, Jew's ear has been known for its anti-coagulant effects. Hence it is worthwhile developing an effective technique to extract active components. To find the optimal extraction condition and to identify the best strain to yield fungal polysaccharide with anti-coagulant activity. Three strains of Jew's ear from Jilin Province, named as 988, DY 18 and FS 02, and three extraction techniques, namely, high intensity pulsed electric fields (HIPEF), microwave-assisted extraction method (MAEM) and ultrasonic-assisted extraction method (UAEM), were applied to optimise the extraction conditions. The crude extracts and polysaccharides were further determined for anti-coagulant activities. All extracts prolonged blood clotting time as compared to reagent control. The HIPEF exhibited the most remarkable effect among the three extraction techniques. The anti-coagulant activities of extracts were enhanced with increasing electric field strength when the field strength reached 24 kV/cm. Current results suggest that the HIPEF technique will be an effective method in the manufacture of bioactive natural polysaccharide. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Delirium in the geriatric unit: proton-pump inhibitors and other risk factors.

    Science.gov (United States)

    Otremba, Iwona; Wilczyński, Krzysztof; Szewieczek, Jan

    2016-01-01

    Delirium remains a major nosocomial complication of hospitalized elderly. Predictive models for delirium may be useful for identification of high-risk patients for implementation of preventive strategies. Evaluate specific factors for development of delirium in a geriatric ward setting. Prospective cross-sectional study comprised 675 consecutive patients aged 79.2±7.7 years (66% women and 34% men), admitted to the subacute geriatric ward of a multiprofile university hospital after exclusion of 113 patients treated with antipsychotic medication because of behavioral disorders before admission. Comprehensive geriatric assessments including a structured interview, physical examination, geriatric functional assessment, blood sampling, ECG, abdominal ultrasound, chest X-ray, Confusion Assessment Method for diagnosis of delirium, Delirium-O-Meter to assess delirium severity, Richmond Agitation-Sedation Scale to assess sedation or agitation, visual analog scale and Doloplus-2 scale to assess pain level were performed. Multivariate logistic regression analysis revealed five independent factors associated with development of delirium in geriatric inpatients: transfer between hospital wards (odds ratio [OR] =2.78; confidence interval [CI] =1.54-5.01; P=0.001), preexisting dementia (OR =2.29; CI =1.44-3.65; Pfall incidents (OR =1.76; CI =1.17-2.64; P=0.006), and use of proton-pump inhibitors (OR =1.67; CI =1.11-2.53; P=0.014). Transfer between hospital wards, preexisting dementia, previous delirium incidents, previous fall incidents, and use of proton-pump inhibitors are predictive of development of delirium in the geriatric inpatient setting.

  15. Assessment of the effects of dalteparin on coagulation variables and determination of a treatment schedule for use in cats.

    Science.gov (United States)

    Schönig, Jette C; Mischke, Reinhard H

    2016-07-01

    OBJECTIVE To determine a treatment protocol for SC administration of dalteparin to cats on the basis of currently available detailed pharmacokinetic data and to assess the effect of SC administration of dalteparin to cats on coagulation variables such as activated partial thromboplastin time (aPTT), thrombin time, and results for thromboelastometry, compared with effects on anti-activated coagulation factor X (anti-Xa) activity. ANIMALS 6 healthy domestic shorthair cats. PROCEDURES Cats received 14 injections of dalteparin (75 anti-Xa U/kg, SC) at 6-hour intervals. Blood samples were collected before and 2 hours after the first and second injections on days 1, 2, and 4. Anti-Xa activity was measured by use of a chromogenic substrate assay, aPTT and thrombin time were measured by use of an automated coagulometer, and viscoelastic measurements were obtained with thromboelastrometry. RESULTS 2 hours after the second injection, the target peak anti-Xa activity range of 0.5 to 1.0 U/mL was achieved in all cats, whereas median trough values remained below this range. Peak anti-Xa activity had only minimal effects on coagulation variables; the maximum median ratio for aPTT (in relationship to the value before the first dalteparin injection) was 1.23. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study indicated that this treatment protocol resulted in reproducible anti-Xa activity in cats that was mostly within the targeted peak range of anti-Xa activity recommended for humans. Treatment in accordance with this protocol may not require routine coagulation monitoring of cats, but this must be confirmed in feline patients.

  16. Neutralisation of the anti-coagulant effects of heparin by histones in blood plasma and purified systems.

    Science.gov (United States)

    Longstaff, Colin; Hogwood, John; Gray, Elaine; Komorowicz, Erzsebet; Varjú, Imre; Varga, Zoltán; Kolev, Krasimir

    2016-03-01

    Neutrophil extracellular traps (NETs) composed primarily of DNA and histones are a link between infection, inflammation and coagulation. NETs promote coagulation and approaches to destabilise NETs have been explored to reduce thrombosis and treat sepsis. Heparinoids bind histones and we report quantitative studies in plasma and purified systems to better understand physiological consequences. Unfractionated heparin (UFH) was investigated by activated partial thromboplastin time (APTT) and alongside low-molecular-weight heparins (LMWH) in purified systems with thrombin or factor Xa (FXa) and antithrombin (AT) to measure the sensitivity of UFH or LMWH to histones. A method was developed to assess the effectiveness of DNA and non-anticoagulant heparinoids as anti-histones. Histones effectively neutralised UFH, the IC50 value for neutralisation of 0.2 IU/ml UFH was 1.8 µg/ml histones in APTT and 4.6 µg/ml against 0.6 IU/ml UFH in a purified system. Histones also inhibited the activities of LMWHs with thrombin (IC50 6.1 and 11.0 µg/ml histones, for different LMWHs) or FXa (IC50 7.8 and 7.0 µg/ml histones). Direct interactions of UFH and LMWH with DNA and histones were explored by surface plasmon resonance, while rheology studies showed complex effects of histones, UFH and LMWH on clot resilience. A conclusion from these studies is that anticoagulation by UFH and LMWH will be compromised by high affinity binding to circulating histones even in the presence of DNA. A complete understanding of the effects of histones, DNA and heparins on the haemostatic system must include an appreciation of direct effects on fibrin and clot structure.

  17. Hemodialysis in a patient with severe hemophilia A and factor VIII inhibitor.

    Science.gov (United States)

    Gopalakrishnan, Natarajan; Usha, Thiruvengadam; Thopalan, Balasubramaniyan; Dhanapriya, Jeyachandran; Dineshkumar, Thanigachalam; Thirumalvalavan, Kaliaperumal; Sakthirajan, Ramanathan

    2016-10-01

    Hemophilia A is a hereditary X-linked recessive disease caused by mutations in the gene encoding factor VIII (FVIII), occurring in 1 out of 10,000 persons. Life expectancy and quality of life have dramatically improved recently in patients with hemophilia. Chronic kidney disease and need for renal replacement therapy in these patients are rare. The development of inhibitors to FVIII is the most serious complication of hemophilia and makes treatment of bleeds very challenging. We describe here a 28-year-old male patient with severe hemophilia A with presence of factor VIII inhibitor, who had end stage renal disease. Central venous access device was inserted along with infusion of factor eight inhibitor bypass activity before and after the procedure. He is currently on thrice weekly hemodialysis and doing well for 6 months without bleeding episodes. To our knowledge, hemophilia A with factor VIII inhibitor managed with hemodialysis has not been reported so far. © 2016 International Society for Hemodialysis.

  18. Enhanced WWTP effluent organic matter removal in hybrid ozonation-coagulation (HOC) process catalyzed by Al-based coagulant

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Xin [School of Environmental and Municipal Engineering, Xi’an University of Architecture and Technology, Xi’an, Shaanxi Province, 710055 (China); Jin, Pengkang, E-mail: pkjin@hotmail.com [School of Environmental and Municipal Engineering, Xi’an University of Architecture and Technology, Xi’an, Shaanxi Province, 710055 (China); Hou, Rui [School of Environmental and Municipal Engineering, Xi’an University of Architecture and Technology, Xi’an, Shaanxi Province, 710055 (China); Yang, Lei [Department of Materials Science and Engineering, Monash University, Clayton, VIC, 3800 (Australia); Wang, Xiaochang C., E-mail: xcwang@xauat.edu.cn [School of Environmental and Municipal Engineering, Xi’an University of Architecture and Technology, Xi’an, Shaanxi Province, 710055 (China)

    2017-04-05

    Highlights: • A novel HOC process was firstly put forward to apply in wastewater reclamation. • Interactions between ozone and Al-based coagulants was found in the HOC process. • Ozonation can be catalyzed and enhanced by Al-based coagulants in the HOC process. • HOC process showed better organics removal than pre-ozonation-coagulation process. - Abstract: A novel hybrid ozonation-coagulation (HOC) process was developed for application in wastewater reclamation. In this process, ozonation and coagulation occurred simultaneously within a single unit. Compared with the conventional pre-ozonation-coagulation process, the HOC process exhibited much better performance in removing dissolved organic matters. In particular, the maximal organic matters removal efficiency was obtained at the ozone dosage of 1 mgO{sub 3}/mg DOC at each pH value (pH 5, 7 and 9). In order to interpret the mechanism of the HOC process, ozone decomposition was monitored. The results indicated that ozone decomposed much faster in the HOC process. Moreover, by using the reagent of O{sub 3}-resistant hydroxyl radical (·OH) probe compound, para-chlorobenzoic acid (pCBA), and electron paramagnetic resonance (EPR) analysis, it was observed that the HOC process generated higher content of ·OH compared with pre-ozonation process. This indicates that the ·OH oxidation reaction as the key step can be catalyzed and enhanced by Al-based coagulants and their hydrolyzed products in this developed process. Thus, based on the catalytic effects of Al-based coagulants on ozonation, the HOC process provides a promising alternative to the conventional technology for wastewater reclamation in terms of higher efficiency.

  19. Preoperative Detailed Coagulation Tests Are Required in Patients With Noonan Syndrome.

    Science.gov (United States)

    Morice, Anne; Harroche, Annie; Cairet, Pascale; Khonsari, Roman H

    2017-12-29

    Patients with Noonan syndrome often require surgery at young ages. They are at high risk of perioperative bleeding from coagulation defects that might not have been detected by routine screening. These risks are rarely described in the oral and maxillofacial surgery (OMS) literature. The aim of this study was to evaluate the perioperative bleeding risks associated with Noonan syndrome and to propose preoperative guidelines. This report describes a retrospective case series of patients with Noonan syndrome who underwent OMS procedures during a continuous observational period (2013 through 2016) in the authors' center. Clinical data, blood screening test results, and perioperative bleeding were analyzed. Five patients (age, 4 to 20 yr) with Noonan syndrome who underwent OMS procedures were included in this study. One patient presented a spontaneous bleeding tendency (epistaxis requiring cauterization). Blood screening showed clotting defects in 3 patients. One patient presented abnormal perioperative bleeding owing to a mild defect in factor XI. Patients with Noonan syndrome must be referred to a hematologist for specific preoperative investigations and for adapted perioperative management. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  20. Normal saline influences coagulation and endothelial function after traumatic brain injury and hemorrhagic shock in pigs

    DEFF Research Database (Denmark)

    Dekker, Simone E; Sillesen, Martin; Bambakidis, Ted

    2014-01-01

    ), colloids (Hextend [HEX]), and fresh frozen plasma (FFP) resuscitation are associated with differential effects on coagulation and endothelial systems. METHODS: We subjected 15 Yorkshire swine to TBI and HS (40% blood volume), and kept in HS for 2 hours before resuscitation with NS, HEX, or FFP. Markers......BACKGROUND: Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related deaths. These insults disrupt coagulation and endothelial systems. This study investigated whether previously reported differences in lesion size and brain swelling during normal saline (NS...... of endothelial activation (E-selectin, Intercellular adhesion molecule [ICAM]-1), coagulation activation (prothrombin fragment 1 + 2), and natural anticoagulation (activated protein C [aPC]) were determined in serum and brain whole cell lysates. RESULTS: Serum levels of aPC were greater in the NS group (203 ± 30...

  1. Incidence and Risk Factors of Coagulation Profile Derangement After Liver Surgery: Implications for the Use of Epidural Analgesia-A Retrospective Cohort Study.

    Science.gov (United States)

    Jacquenod, Pierre; Wallon, Grégoire; Gazon, Mathieu; Darnis, Benjamin; Pradat, Pierre; Virlogeux, Victor; Farges, Olivier; Aubrun, Frédéric

    2018-04-01

    Hepatic surgery is a major abdominal surgery. Epidural analgesia may decrease the incidence of postoperative morbidities. Hemostatic disorders frequently occur after hepatic resection. Insertion or withdrawal (whether accidental or not) of an epidural catheter during coagulopathic state may cause an epidural hematoma. The aim of the study is to determine the incidence of coagulopathy after hepatectomy, interfering with epidural catheter removal, and to identify the risk factors related to coagulopathy. We performed a retrospective review of a prospective, multicenter, observational database including patients over 18 years old with a history of liver resection. Main collected data were the following: age, preexisting cirrhosis, Child-Pugh class, preoperative and postoperative coagulation profiles, extent of liver resection, blood loss, blood products transfused during surgery. International normalized ratio (INR) ≥1.5 and/or platelet count <80,000/mm defined coagulopathy according to the neuraxial anesthesia guidelines. A logistic regression analysis was performed to assess the association between selected factors and a coagulopathic state after hepatic resection. One thousand three hundred seventy-one patients were assessed. Seven hundred fifty-nine patients had data available about postoperative coagulopathy, which was observed in 53.5% [95% confidence interval, 50.0-57.1]. Maximum derangement in INR occurred on the first postoperative day, and platelet count reached a trough peak on postoperative days 2 and 3. In the multivariable analysis, preexisting hepatic cirrhosis (odds ratio [OR] = 2.49 [1.38-4.51]; P = .003), preoperative INR ≥1.3 (OR = 2.39 [1.10-5.17]; P = .027), preoperative platelet count <150 G/L (OR = 3.03 [1.77-5.20]; P = .004), major hepatectomy (OR = 2.96 [2.07-4.23]; P < .001), and estimated intraoperative blood loss ≥1000 mL (OR = 1.85 [1.08-3.18]; P = .025) were associated with postoperative coagulopathy. Coagulopathy is frequent (53

  2. CD8+ T Cells Specific to Apoptosis-Associated Antigens Predict the Response to Tumor Necrosis Factor Inhibitor Therapy in Rheumatoid Arthritis.

    Directory of Open Access Journals (Sweden)

    Alessandra Citro

    Full Text Available CD8+ T cells specific to caspase-cleaved antigens derived from apoptotic T cells (apoptotic epitopes represent a principal player in chronic immune activation, which is known to amplify immunopathology in various inflammatory diseases. The purpose of the present study was to investigate the relationship involving these autoreactive T cells, the rheumatoid arthritis immunopathology, and the response to tumor necrosis factorinhibitor therapy. The frequency of autoreactive CD8+ T cells specific to various apoptotic epitopes, as detected by both enzyme-linked immunospot assay and dextramers of major histocompatibility complex class I molecules complexed with relevant apoptotic epitopes, was longitudinally analyzed in the peripheral blood of rheumatoid arthritis patients who were submitted to etanercept treatment (or other tumor necrosis factor inhibitors as a control. The percentage of apoptotic epitope-specific CD8+ T cells was significantly higher in rheumatoid arthritis patients than in healthy donors, and correlated with the disease activity. More important, it was significantly more elevated in responders to tumor necrosis factorinhibitor therapy than in non-responders before the start of therapy; it significantly dropped only in the former following therapy. These data indicate that apoptotic epitope-specific CD8+ T cells may be involved in rheumatoid arthritis immunopathology through the production of inflammatory cytokines and that they may potentially represent a predictive biomarker of response to tumor necrosis factorinhibitor therapy to validate in a larger cohort of patients.

  3. THE RATIONALIZATION OF THE PARAMETERS OF MILK PROTEINS’ THERMO ACID COAGULATION BY BERRY COAGULANTS

    Directory of Open Access Journals (Sweden)

    Olena GREK

    2017-03-01

    Full Text Available This paper presents the results related to the influence of berry coagulant amount, its proactive acidity and duration of thermo acid coagulation on the process of milk proteins’ sedimentation. In the present work, the regression equations and response surface analysis were used to design and optimize an industrial bioprocess. Increase in the berry coagulant amount to 11 % and reduction of active acidity to 2.4 units were determined. pH up to 3 minutes is characterized by the highest processes of destabilization. Moreover, it improves the organoleptic properties and has the biggest impact on the yield of protein-berry clot (to 25 % and active acidity.

  4. Fiber-based optic sensor for detecting human blood clot: present and future revival

    Science.gov (United States)

    Elshikeri, Nada; Bakhtiar, Hazri

    2018-05-01

    Sustaining human’s life-frame away from being impeded by the clot - ghost term, we attempt to approach a mobile fiber-based optical sensor (f-s) for detecting blood clot in a blood vessel (intra-arteries/veins). Blood vessels are the part of the circulatory system that transport blood throughout the human body, thus their significance of being protected arise to the monograph focus. MRI (magnetic resonance imaging), X-rays and other medical instruments are diagnostic immobility techniques with a slackest interval. The corer causation of fiber-based optical sensor is to detect a clump of blood in the bloodstream by providing a prompt mobile diagnostic intervals preserving last-minutes-breath of human’s life. The detector (f-s) has been etched by diluting sulphuric acid ~10% at certain zone to sensate its function. The in-vitro monograph peaks its maximal monitoring when the sensor is attached to Raman Spectroscopy (RS) setup. RS quantifies the relative intensities of fibrinogen bond, which is the first type of blood coagulation elements of blood plasma. Blood coagulation parameters are the major concern of the monograph investigation, such as total haemoglobin (tHb), clotting reaction time (t), clot progression time (t2), maximum clot amplitude (ma) and mean refractive index (r). A blood sample will be drawn from the patient and after centrifugation to separate blood plasma from its constituents, then an immediate sloshing of blood plasma in the (f-s) packet which has its plug-in to RS. Estimating the quantitative analysis of blood sample concentration, RS will determine the presence of coagulation in terms of intensity and medical procedures will dominate the treatment process. Thus, the suggestive monograph provides a definite instrument for investigating blood coagulation intra-arteries/veins promptly.

  5. Small molecule inhibitors of anthrax edema factor.

    Science.gov (United States)

    Jiao, Guan-Sheng; Kim, Seongjin; Moayeri, Mahtab; Thai, April; Cregar-Hernandez, Lynne; McKasson, Linda; O'Malley, Sean; Leppla, Stephen H; Johnson, Alan T

    2018-01-15

    Anthrax is a highly lethal disease caused by the Gram-(+) bacteria Bacillus anthracis. Edema toxin (ET) is a major contributor to the pathogenesis of disease in humans exposed to B. anthracis. ET is a bipartite toxin composed of two proteins secreted by the vegetative bacteria, edema factor (EF) and protective antigen (PA). Our work towards identifying a small molecule inhibitor of anthrax edema factor is the subject of this letter. First we demonstrate that the small molecule probe 5'-Fluorosulfonylbenzoyl 5'-adenosine (FSBA) reacts irreversibly with EF and blocks enzymatic activity. We then show that the adenosine portion of FSBA can be replaced to provide more drug-like molecules which are up to 1000-fold more potent against EF relative to FSBA, display low cross reactivity when tested against a panel of kinases, and are nanomolar inhibitors of EF in a cell-based assay of cAMP production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Blood loss predictive factors and transfusion practice during percutaneous nephrolithotomy of kidney stones: a prospective study [version 1; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Firtantyo Adi Syahputra

    2016-06-01

    Full Text Available Objectives Bleeding is the most common complication of percutaneous nephrolithotomy (PCNL. Injudicious transfusion is frequently performed in current practice, even though it is not always needed. This study aimed to identify the predictive factors of blood loss in the PCNL procedure and evaluate the perioperative transfusion practice.   Methods A prospective study of PCNL was randomly performed by two consultants of endo-urology at our institution. The inclusion criteria were adults with kidney pelvic stones >20 mm or stone in inferior calyx >10 mm or staghorn stone. Those with coagulopathy, under anti-coagulant treatment or open conversion were excluded. A full blood count was taken at baseline and during 12, 24, 36, 72-hours post-operatively. Factors such as stone burden, sex, body surface area, shifting of hematocrit level and amount of blood transfused were analyzed statistically using line regression to identify the predictive factors of total blood loss (TBL.   Results Eighty-five patients were enrolled in this study. Mean TBL was 560.92 ± 428.43 mL for both endo-urology surgeons. Stone burden was the most influential factor for TBL (p=0.037. Our results revealed that TBL (mL = -153.379 + 0.229 × stone burden (mm2 + 0.203 x baseline serum hematocrit (%; thus considerably predicted the need for blood transfusion. A total of 87.1% patients did not receive perioperative transfusion, 3.5% received intra-operative transfusion, 7.1% received post-operative transfusion, 23% had both intra and post-operative transfusion, resulting in a cross-matched transfusion ratio of 7.72. Mean perioperative blood transfused was 356.00 ± 145.88 mL.

  7. Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

    Science.gov (United States)

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

  8. Hemorrhoidectomy: pedicle ligation vs pedicle coagulation

    International Nuclear Information System (INIS)

    Shaikh, B.S.; Balaoch, I.B.; Sohu, K.M.

    2015-01-01

    Objective: To compare the outcome of pedicle ligation vs pedicle coagulation haemorrhoidectomy. Methodology: This comparative prospective study was carried out at Department of Surgery, Ghulam Muhammad Maher Medcial College Hospital, Sukkur, Pakistan from January 2011 to January 2013 and included 300 patients of hemorrhoids. After routine workup, patients were randomly divided into two equal groups with one group receiving pedicle ligation and other pedicle coagulation for hemorrhoidectomy. Postoperatively they were followed for a period of 8 weeks for complications including pain, urinary retention, bleeding and anal stricture. Pain was recorded up to 10th postoperative day on the basis of visual analogue scale. Results: Mean age was 45 years and male to female ratio was 1.7:1. Mean operative time in pedicle ligation group was 15 min (range 14-20 min) and 17 min (15-25 min) in pedicle coagulation group. In Pedicle ligation group, pain was worst in 35 patients, moderate in 85 and mild in 30 patients; on the other hand in pedicle coagulation group, just 09 patients experienced worst pain. Urinary retention was observed in 44 patients in pedicle ligation group and 19 in pedicle coagulation group. Five patients in pedicle ligation group developed bleeding after their discharge from hospital; 7 patients in pedicle coagulation group reported secondary bleeding. Anal stricture was a rare complication and was found equally common in both the groups. Conclusion: Conventional hemorrhoidectomy with pedicle coagulation is an effective treatment modality for hemorrhoids and is associated with less chance of postoperative anal pain and urinary retention. (author)

  9. Pro- and non-coagulant forms of non-cell-bound tissue factor in vivo

    NARCIS (Netherlands)

    Sturk-Maquelin, K. N.; Nieuwland, R.; Romijn, F. P. H. T. M.; Eijsman, L.; Hack, C. E.; Sturk, A.

    2003-01-01

    Background: Concentrations of non-cell-bound (NCB; soluble) tissue factor (TF) are elevated in blood collecting in the pericardial cavity of patients during cardiopulmonary bypass (CPB). Previously, we reported microparticles supporting thrombin generation in such blood samples. In this study we

  10. KRN633, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, induces intrauterine growth restriction in mice.

    Science.gov (United States)

    Abe, Naomichi; Nakahara, Tsutomu; Morita, Akane; Wada, Yoshiko; Mori, Asami; Sakamoto, Kenji; Nagamitsu, Tohru; Ishii, Kunio

    2013-08-01

    We previously reported that treatment with KRN633, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, during mid-pregnancy caused intrauterine growth restriction resulting from impairment of blood vessel growth in the labyrinthine zone of the placenta and fetal organs. However, the relative sensitivities of blood vessels in the placenta and fetal organs to vascular endothelial growth factor (VEGF) inhibitors have not been determined. In this study, we aimed to examine the effects of KRN633 on the vasculatures of organs in mother mice and their newborn pups by immunohistochemical analysis. Pregnant mice were treated daily with KRN633 (5 mg/kg) either from embryonic day 13.5 (E13.5) to E17.5 or from E13.5 to the day of delivery. The weights of the pups of KRN633-treated mice were lower than those of the pups of vehicle-treated mothers. However, no significant difference in body weight was observed between the vehicle- and KRN633-treated mice. The vascular development in the organs (the pancreas, kidney, and intestine) and intestinal lymphatic formation of the pups of KRN633-treated mothers was markedly impaired. In contrast, the KRN633 treatment showed no significant effect on the vascular beds in the organs, including the labyrinthine zone of the placenta, of the mother mice. These results suggest that blood vessels in fetal organs are likely to be more sensitive to reduced VEGF signaling than those in the mother. A partial loss of VEGF function during pregnancy could suppress vascular growth in the fetus without affecting the vasculature in the mother mouse, thereby increasing the risk of intrauterine growth restriction. © 2013 Wiley Periodicals, Inc.

  11. Blood donors and factors impacting the blood donation decision: motives for donating blood in Turkish sample.

    Science.gov (United States)

    Karacan, Eda; Cengiz Seval, Guldane; Aktan, Zeynep; Ayli, Meltem; Palabiyikoglu, Refia

    2013-12-01

    Donations in Turkey are insufficient to cover the high transfusion needs arising from large numbers of thalassemia and sickle cell anemia patients and increasing demands for blood due to advanced surgery and cancer treatment. The most acceptable means to get blood is voluntary blood donation and the blood donor system in Turkey mostly depends on a combination of voluntary and involuntary donors. The main aim of this study is to explore the motivations of Turkish voluntary blood donors toward blood donation and to determine predictors of blood donation motivation. A cross-sectional sample survey of active blood donors in Ankara, Turkey was conducted. The sample consisted of 189 male volunteer blood donor adults. Donors filled in a self-administered questionnaire including the measures of demographic information, empathetic concern, altruism, social responsibility and blood donation motivation questionnaire during donation. Factor analysis of Blood Donation Motivation Measure with varimax rotation revealed a three-factor solution named as "values and moral duty", "positive feelings and esteem" and "self-benefit and external reasons". The results with regression analyses showed that only social responsibility had an significant effect independent of age, income, and education on blood donation motivation. These result reflects that blood donation motivation not only linked to a high degree of altruistic reasons, but also to a combination of some self-regarding motives. Additionally, feelings of empathy or altruism may be less strong at the time the decision to help, other factors may have a larger influence on helping decisions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. The kunitz protease inhibitor domain of protease nexin-2 inhibits factor XIa and murine carotid artery and middle cerebral artery thrombosis

    Science.gov (United States)

    Wu, Wenman; Li, Hongbo; Navaneetham, Duraiswamy; Reichenbach, Zachary W.; Tuma, Ronald F.

    2012-01-01

    Coagulation factor XI (FXI) plays an important part in both venous and arterial thrombosis, rendering FXIa a potential target for the development of antithrombotic therapy. The kunitz protease inhibitor (KPI) domain of protease nexin-2 (PN2) is a potent, highly specific inhibitor of FXIa, suggesting its possible role in the inhibition of FXI-dependent thrombosis in vivo. Therefore, we examined the effect of PN2KPI on thrombosis in the murine carotid artery and the middle cerebral artery. Intravenous administration of PN2KPI prolonged the clotting time of both human and murine plasma, and PN2KPI inhibited FXIa activity in both human and murine plasma in vitro. The intravenous administration of PN2KPI into WT mice dramatically decreased the progress of FeCl3-induced thrombus formation in the carotid artery. After a similar initial rate of thrombus formation with and without PN2KPI treatment, the propagation of thrombus formation after 10 minutes and the amount of thrombus formed were significantly decreased in mice treated with PN2KPI injection compared with untreated mice. In the middle cerebral artery occlusion model, the volume and fraction of ischemic brain tissue were significantly decreased in PN2KPI-treated compared with untreated mice. Thus, inhibition of FXIa by PN2KPI is a promising approach to antithrombotic therapy. PMID:22674803

  13. New models of hemostasis.

    Science.gov (United States)

    McMichael, Maureen

    2012-05-01

    Hemostasis is an essential protective mechanism that depends on a delicate balance of procoagulant and anticoagulant processes. The waterfall/cascade models of coagulation are useful for understanding several essential steps of coagulation in vitro. These have resulted in the creation of the plasma-based tests used commonly and the ability to identify deficiencies in the extrinsic, intrinsic, and common pathways of coagulation. The model was also essential in elucidating the role of several of the inhibitors of coagulation and is currently used to demonstrate coagulation as it occurs in plasma in a static environment that is devoid of endothelial interactions. The intrinsic pathway originally described by these models does not appear to be essential for in vivo hemostasis but may play a role in pathologic thrombosis. The waterfall/cascade models' lack of cellular elements sets the stage for the cell-based model of coagulation. The cell-based model of blood coagulation, which includes the varied, complicated network of factors necessary for appropriate in vivo coagulation to occur, was the next step in the evolution of our understanding of coagulation. Recently, researchers have focused on real-time, in vivo models of hemostasis and this research reveals unexpected phenomena. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system.

    Science.gov (United States)

    Schernthaner, Guntram; Mogensen, Carl Erik; Schernthaner, Gerit-Holger

    2014-09-01

    Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway. © The Author(s) 2014.

  15. Coagulants modulate the hypocholesterolemic effect of tofu ...

    African Journals Online (AJOL)

    hope&shola

    2006-02-02

    Feb 2, 2006 ... The recent increase in soymilk and tofu (coagulated soymilk) consumption especially in western countries is due to the recognition of the health benefits of soy foods. The amount and the type of coagulated biomolecules (such as isoflavones) vary with the type of coagulant, and this will inevitable alter their ...

  16. Haematological and biochemical characteristics of the splenic effluent blood in schistosomal patients undergoing splenectomy

    Directory of Open Access Journals (Sweden)

    Andy Petroianu

    Full Text Available OBJECTIVE: To assess hematological and biochemical features of splenic effluent blood and their influence on the rise of hematological values after splenectomy. METHODS: we studied 20 patients undergoing surgical treatment for schistosomatic portal hypertension. We collected blood samples for CBC, coagulation, bilirubin and albumin in the splenic vein (perioperative and peripheral blood (immediately pre and postoperative periods. RESULTS: the splenic blood showed higher values of red blood cells, hemoglobin, hematocrit, platelet count, total leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils, as well as reduction of laboratory coagulation parameters in relation to peripheral blood collected preoperatively. In the postoperative peripheral blood there was an increase in the overall leukocytes and in their neutrophil component, and decreased levels of basophils, eosinophils and lymphocytes. The other postoperative variables of complete blood count and coagulation tests were not different compared with the splenic blood. The albumin values were lower postoperatively when compared to preoperative and splenic blood. There were higher values of direct bilirubin in the postoperative period when compared with the preoperative and splenic blood. Postoperative indirect bilirubin was lower compared to its value in the splenic blood. CONCLUSION: hematological and biochemical values of splenic effluent blood are higher than those found in peripheral blood in the presence of schistosomal splenomegaly. However, the splenic blood effluent is not sufficient to raise the blood levels found after splenectomy.

  17. Inhibitors of plasmodial serine hydroxymethyltransferase (SHMT): cocrystal structures of pyrazolopyrans with potent blood- and liver-stage activities.

    Science.gov (United States)

    Witschel, Matthias C; Rottmann, Matthias; Schwab, Anatol; Leartsakulpanich, Ubolsree; Chitnumsub, Penchit; Seet, Michael; Tonazzi, Sandro; Schwertz, Geoffrey; Stelzer, Frank; Mietzner, Thomas; McNamara, Case; Thater, Frank; Freymond, Céline; Jaruwat, Aritsara; Pinthong, Chatchadaporn; Riangrungroj, Pinpunya; Oufir, Mouhssin; Hamburger, Matthias; Mäser, Pascal; Sanz-Alonso, Laura M; Charman, Susan; Wittlin, Sergio; Yuthavong, Yongyuth; Chaiyen, Pimchai; Diederich, François

    2015-04-09

    Several of the enzymes related to the folate cycle are well-known for their role as clinically validated antimalarial targets. Nevertheless for serine hydroxymethyltransferase (SHMT), one of the key enzymes of this cycle, efficient inhibitors have not been described so far. On the basis of plant SHMT inhibitors from an herbicide optimization program, highly potent inhibitors of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) SHMT with a pyrazolopyran core structure were identified. Cocrystal structures of potent inhibitors with PvSHMT were solved at 2.6 Å resolution. These ligands showed activity (IC50/EC50 values) in the nanomolar range against purified PfSHMT, blood-stage Pf, and liver-stage P. berghei (Pb) cells and a high selectivity when assayed against mammalian cell lines. Pharmacokinetic limitations are the most plausible explanation for lack of significant activity of the inhibitors in the in vivo Pb mouse malaria model.

  18. Comparison of Platelet Transfusion as Fresh Whole Blood Versus Apheresis Platelets for Massively Transfused Combat Trauma patients

    Science.gov (United States)

    2011-02-01

    Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch JM, Galloway B. Predicting life-threatening coagulopathy in the massively transfused trauma patient...BM, Lloyd JV. The stability of coagulation factors in stored blood. Aust N Z J Surg 1982;52:265-9. 43. Scott E, Puca K, Heraly J, Gottschall J

  19. Risk Factor for Diabetes Mellitus and High Blood Glucose With HMG-CoA Reductase Inhibitors Using a Postmarketing Surveillance Database in Japan.

    Science.gov (United States)

    Hashiguchi, Masayuki; Maruyama, Junya; Shimizu, Mikiko; Takahashi, Daichi; Shiga, Tsuyoshi

    2018-02-20

    To investigate whether 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) use is associated with an increased risk of diabetes mellitus and hyperglycemia, we performed a nested case-control study using a postmarketing surveillance database in Japan. The database cohort included 26,849 cases of statin use and 5308 cases of other lipid-lowering drug use in patients with hyperlipidemia. Participants received at least 1 type of statin, had a clear medication history of statin use, and had no complications of diabetes mellitus. Cases were defined as onset of diabetes mellitus or hyperglycemia during statin intake. For each case, 20 controls were randomly selected and matched by time point. The factors associated with an increased risk of diabetes mellitus and hyperglycemia during statin intake examined included sex, age, body mass index, statin use duration, complications, concomitant medication, and clinical laboratory tests. Statin-associated diabetes mellitus or hyperglycemia was identified based on abnormal elevation of blood glucose concentrations beyond the reference range. A total of 19,868 patients met the inclusion criteria, of whom 24 were patients in the case group. Two complicating factors, fatty liver (adjusted odds ratio 16.10) and hyperuricemia (adjusted odds ratio 28.96), were extracted for onset of diabetes mellitus or hyperglycemia. Nonalcoholic fatty liver was associated with diabetes mellitus, obesity, and insulin resistance, and hyperuricemia was associated with lifestyle. This study suggested that the onset of diabetes mellitus or hyperglycemia might be increased with statin use in patients with complications of fatty liver and hyperuricemia. © 2018, The American College of Clinical Pharmacology.

  20. Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of deep vein thrombosis.

    Science.gov (United States)

    Robertson, Lindsay; Kesteven, Patrick; McCaslin, James E

    2015-06-30

    Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately 1 in 1,000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of novel oral anticoagulants (NOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the treatment of DVT. To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the treatment of DVT. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). We searched clinical trials databases for details of ongoing or unpublished studies and the reference lists of relevant articles retrieved by electronic searches for additional citations. We included randomised controlled trials in which people with a DVT confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor for the treatment of DVT. Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third review author (PK). We performed meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent VTE and PE. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes using an odds ratio (OR) with a 95% confidence interval (CI). We included

  1. Intraventricular hemorrhage in preterm infants and coagulation--ambivalent perspectives?

    Science.gov (United States)

    Kuperman, Amir A; Brenner, Benjamin; Kenet, Gili

    2013-01-01

    Intraventricular hemorrhage (IVH) is a major complication of preterm birth, and large hemorrhages may yield significant future disability. During the last few decades, the survival of preterm infants has increased dramatically. Nevertheless, morbidity is still a major problem especially for very young and extremely low birth weight infants. As both, mortality and incidence of morbidities known to influence outcome, show a weekly decline with increasing gestational age, prematurity and low birth weight have been identified as major risk factors for IVH occurrence. This stems probably from the increased vulnerability of the premature germinal matrix as well as the physiologically impaired hemostasis, demonstrated in neonates. The hypothesis that a severe coagulation deficiency in the premature newborn could be a major contributing factor for IVH has been suggested, and small open label interventional studies targeting the premature coagulation system have been conducted with ethamsylate, vitamin K, fresh frozen plasma, recombinant activated factor VII and prothrombin complex concentrate. Nevertheless, potential venous origin of hemorrhages, which may be related to thrombophilic risk factors, has also been discussed. The following manuscript will focus upon IVH pathogenesis and address potential therapies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Enhancement of sedimentation and coagulation with static magnetic field

    Science.gov (United States)

    Zieliński, Marcin; Dębowski, Marcin; Hajduk, Anna; Rusanowska, Paulina

    2017-11-01

    The static magnetic field can be an alternative method for wastewater treatment. It has been proved that this physical factor, accelerates the biochemical processes, catalyzes advanced oxidation, intensifies anaerobic and aerobic processes or reduces swelling of activated sludge. There are also reports proving the positive impact of the static magnetic field on the coagulation and sedimentation, as well as the conditioning and dewatering of sludge. In order to be applied in larger scale the published results should be verified and confirmed. In the studies, the enhancement of sedimentation by the static magnetic field was observed. The best sedimentation was noted in the experiment, where magnetizers were placed on activated sludge bioreactor and secondary settling tank. No effect of the static magnetic field on coagulation with the utilization of PIX 113 was observed. However, the static magnetic field enhanced coagulation with the utilization of PAX-XL9. The results suggest that increased sedimentation of colloids and activated sludge, can in practice mean a reduction in the size of the necessary equipment for sedimentation with an unchanged efficiency of the process.

  3. Rheological behavior of raw natural rubber coagulated by microorganisms

    Directory of Open Access Journals (Sweden)

    Zhifen Wang

    2014-01-01

    Full Text Available Tests of the strain sweep, frequency sweep and stress relaxation for raw natural rubber coagulated by microorganisms (NR-m and raw natural rubber coagulated by acid (NR-a were carried out with the use of a rubber process analyzer (RPA. The results showed that the storage torque, complex viscosity of NR-m were higher than those of NR-a while the loss factor was lower. The effect of temperature on viscosity of raw NR was studied following the Arrhenious-Frenkel-Eyring model. The viscous flow behavior of NR-m was poorer than those of NR-a. Furthermore, stress relaxation measurements of raw NR showed a longer period of relaxation for NR-m.

  4. Risk of transmission of Creutzfeldt-Jakob disease via blood and blood products. The French risk-analysis over the last 15 years.

    Science.gov (United States)

    Martin, M; Trouvin, J-H

    2013-09-01

    Risk of transmission of Creutzfeldt-Jakob disease (infectious agent, responsible of spongiform encephalopathy) via blood and blood components (including the plasma-derived medicinal products such as coagulation factors and immunoglobulins) have been a subject of concern for Health authorities since the early 1980s, with a regain of interest in the 1990s, with the bovine spongiform encephalopathy outbreak followed few years after with the notification of the first cases of variant Creutzfeldt-Jakob disease in humans. The risk-analysis and measures taken by the French authorities in the period 1990-2010 will be described with the various assumptions and working hypothesis used and revisited as new findings become available. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Coagulant recovery and reuse for drinking water treatment.

    Science.gov (United States)

    Keeley, James; Jarvis, Peter; Smith, Andrea D; Judd, Simon J

    2016-01-01

    Coagulant recovery and reuse from waterworks sludge has the potential to significantly reduce waste disposal and chemicals usage for water treatment. Drinking water regulations demand purification of recovered coagulant before they can be safely reused, due to the risk of disinfection by-product precursors being recovered from waterworks sludge alongside coagulant metals. While several full-scale separation technologies have proven effective for coagulant purification, none have matched virgin coagulant treatment performance. This study examines the individual and successive separation performance of several novel and existing ferric coagulant recovery purification technologies to attain virgin coagulant purity levels. The new suggested approach of alkali extraction of dissolved organic compounds (DOC) from waterworks sludge prior to acidic solubilisation of ferric coagulants provided the same 14:1 selectivity ratio (874 mg/L Fe vs. 61 mg/L DOC) to the more established size separation using ultrafiltration (1285 mg/L Fe vs. 91 mg/L DOC). Cation exchange Donnan membranes were also examined: while highly selective (2555 mg/L Fe vs. 29 mg/L DOC, 88:1 selectivity), the low pH of the recovered ferric solution impaired subsequent treatment performance. The application of powdered activated carbon (PAC) to ultrafiltration or alkali pre-treated sludge, dosed at 80 mg/mg DOC, reduced recovered ferric DOC contamination to water quality parameters. Several PAC-polished recovered coagulants provided the same or improved DOC and turbidity removal as virgin coagulant, as well as demonstrating the potential to reduce disinfection byproducts and regulated metals to levels comparable to that attained from virgin material. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Magnetic Resonance Mediated Radio Frequency Coagulation for Vascular Repair

    Science.gov (United States)

    Zhao, Ming

    Purpose. Magnetic Resonance Mediated Radiofrequency Coagulation employs the RF heating effect of MRI scanning to coagulate biomaterials for repair of vascular defects. Coagulation of a protein biomaterial by MR-induced RF heating is a novel means to effect repair of defects such as aneurysms or arteriovenous malformations. Our novel method is to coagulate a thermosetting material (such as egg white, which can be used for investigating heat coagulation behavior and MR relaxation properties) delivered endovascularly by catheter and coagulated by RF-induced heating of an intracatheter resonant wire antenna in the scanner. Methods. Experiments were performed on a Siemens 1.5 T MRI scanner and a Bruker 14T NMR spectrometer. Egg white was brought to equilibrium at seven temperatures (20, 30, 40, 50, 60, 70 and 37 °C) in sequence. Measurement of the water spin-lattice relaxation time Ti, spin-spin relaxation time T2, spin-lattice relaxation time in the rotating frame T1p, or full width at half maximum of the MT spectrum were performed at each temperature. Relaxation parameters of raw egg white and egg white after coagulation at 70 °C were measured in the scanner at 20 °C to determine optimum inversion time, echo time and offset frequency for good image contrast between coagulated and uncoagulated protein. Finally, coagulation of egg white within a glass aneurysm phantom by RF heating in the scanner was performed to demonstrate the MR coagulation methodology and the ability to achieve image contrast between coagulated and uncoagulated biomaterial. Results. Water T2, T1p and MT gave the most definitive indication of the change from uncoagulated at low temperature to fully coagulated at 60 °C, while water T1 showed only the expected gradual increase with temperature, and no response to coagulation. MT weighted imaging is expected to be the optimum method to establish the coagulation condition of the biomaterial.

  7. Effect of urokinase thrombolysis on the cardiac function, coagulation, and fibrinolytic system in patients with AMI

    Directory of Open Access Journals (Sweden)

    Zhi-Bin Kuang

    2017-06-01

    Full Text Available Objective: To observe the effect of urokinase thrombolysis on the cardiac function, coagulation, and fibrinolytic system in patients with acute myocardial infarction (AMI. Methods: A total of 39 patients with AMI who were admitted in our hospital from March, 2016 to November, 2016 were included in the study and served as the observation group. The peripheral venous blood before and after thrombolysis was collected. The plasma NTproBNP level, related coagulation factors, and fibrinolysis indicators were detected. The cardiac function before treatment was evaluated. A total of 30 healthy individuals who came for physical examinations were served as the control group for contrastive analysis. Results: The plasma NT-proBNP, Fg, and D-D levels before thrombolysis in the observation group were significantly higher than those in the control group, while PT, APTT, and TT in the observation group were significantly shortened. The plasma NT-proBNP and D-D levels 2-48 h after thrombolysis in the observation group were significantly elevated first and reduced later and reached the peak 4 h after treatment, while PT, APTT, and TT were significantly extended first and shortened later. The plasma Fg level was significantly reduced first and elevated later and reached the minimum 4 h after treatment. During the treatment process, in the observation group, 2 had mucocutaneous hemorrhage, 3 had nasal hemorrhage, and 1 had gingival bleeding, but no gastrointestinal bleeding or cerebral hemorrhage occurred. Conclusions: The thrombolytic therapy can effectively reduce the coagulation activity in patients with AMI, strengthen the fibrinolysis activity, and improve the cardiac function.

  8. Quality of intraoperative autologous blood withdrawal used for retransfusion after cardiopulmonary bypass.

    Science.gov (United States)

    Flom-Halvorsen, Hanne I; Øvrum, Eivind; Øystese, Rolf; Brosstad, Frank

    2003-09-01

    Intraoperative autologous blood withdrawal protects the pooled blood from the deleterious effects of cardiopulmonary bypass. Following reinfusion after cardiopulmonary bypass, the fresh autologous blood contributes to less coagulation abnormalities and reduces postoperative bleeding and the need for allogeneic blood products. However, few data have been available concerning the quality and potential activation of fresh blood stored at room temperature in the operating room. Forty coronary artery bypass grafting patients undergoing a consistent intraoperative and postoperative autotransfusion protocol had a median of 1,000 mL of autologous blood withdrawn before cardiopulmonary bypass. After heparinization the blood was drained from the venous catheter via venous cannula into standard blood bags and stored in the operating room until termination of cardiopulmonary bypass. Samples for hemostatic and inflammatory markers were taken from the pooled blood immediately before it was returned to the patient. There was some activation of platelets in the stored autologous blood, as measured by an increase of beta-thromboglobulin. Indications of thrombin formation, as assessed by plasma levels of thrombin-antithrombin complex and prothrombin fragment 1.2 were not seen, and there was no fibrinolytic activity. The red blood cells remained intact, indicated by the absence of plasma free hemoglobin. As for the inflammatory response, the levels of the terminal complement complex remained stable, and the cytokines tumor necrosis factor-alpha and interleukin 6 levels were not increased during storage. The complement activation products increased minimally, but remained within normal ranges. Except for slight activation of platelets, there was no indication of coagulation, hemolysis, fibrinolysis, or immunologic activity in the autologous blood after approximately 1 hour of operating room storage. The autologous blood was preserved in a condition of high quality, and retransfusion

  9. Coagulation and Mental Disorders

    Directory of Open Access Journals (Sweden)

    Silvia Hoirisch-Clapauch

    2014-10-01

    Full Text Available The neurovascular unit is a key player in brain development, homeostasis, and pathology. Mental stress affects coagulation, while severe mental illnesses, such as recurrent depression and schizophrenia, are associated with an increased thrombotic risk and cardiovascular morbidity. Evidence indicates that the hemostatic system is involved to some extent in the pathogenesis, morbidity, and prognosis of a wide variety of psychiatric disorders. The current review focuses on emerging data linking coagulation and some psychiatric disorders.

  10. Removal of silver nanoparticles by coagulation processes

    International Nuclear Information System (INIS)

    Sun, Qian; Li, Yan; Tang, Ting; Yuan, Zhihua; Yu, Chang-Ping

    2013-01-01

    Highlights: • This study investigated the removal of AgNP suspensions by four regular coagulants. • The optimal removal efficiencies for the four coagulants were achieved at pH 7.5. • The removal efficiency of AgNPs was affected by the natural water characteristics. • TEM and XRD showed that AgNPs or silver-containing NPs were adsorbed onto the flocs. -- Abstract: Commercial use of silver nanoparticles (AgNPs) will lead to a potential route for human exposure via potable water. Coagulation followed by sedimentation, as a conventional technique in the drinking water treatment facilities, may become an important barrier to prevent human from AgNP exposures. This study investigated the removal of AgNP suspensions by four regular coagulants. In the aluminum sulfate and ferric chloride coagulation systems, the water parameters slightly affected the AgNP removal. However, in the poly aluminum chloride and polyferric sulfate coagulation systems, the optimal removal efficiencies were achieved at pH 7.5, while higher or lower of pH could reduce the AgNP removal. Besides, the increasing natural organic matter (NOM) would reduce the AgNP removal, while Ca 2+ and suspended solids concentrations would also affect the AgNP removal. In addition, results from the transmission electron microscopy and X-ray diffraction showed AgNPs or silver-containing nanoparticles were adsorbed onto the flocs. Finally, natural water samples were used to validate AgNP removal by coagulation. This study suggests that in the case of release of AgNPs into the source water, the traditional water treatment process, coagulation/sedimentation, can remove AgNPs and minimize the silver ion concentration under the well-optimized conditions

  11. In vivo recovery and safety of human factor VIII product AAFACT in patients with haemophilia A

    NARCIS (Netherlands)

    Vossebeld, P. J. M.; Tissing, M. H.; van den Berg, H. M.; Leebeek, F. W. G.; de Goede-Bolder, A.; Novakova, I. R. O.; Gerrits, W. B. J.; Peters, M.; Koopman, M. M. W.; Faber, A.; Hiemstra, H.; Grob, P.; Strengers, P. F. W.

    2003-01-01

    AAFACT, a monoclonal purified, solvent/detergent treated human plasma-derived coagulation factor VIII concentrate obtained from plasma of voluntary, non-remunerated blood donors, is manufactured and marketed in the Netherlands by Sanquin Plasma Products since 1995. In a postmarketing surveillance

  12. Optical sensing of anticoagulation status: Towards point-of-care coagulation testing.

    Directory of Open Access Journals (Sweden)

    Diane M Tshikudi

    Full Text Available Anticoagulant overdose is associated with major bleeding complications. Rapid coagulation sensing may ensure safe and accurate anticoagulant dosing and reduce bleeding risk. Here, we report the novel use of Laser Speckle Rheology (LSR for measuring anticoagulation and haemodilution status in whole blood. In the LSR approach, blood from 12 patients and 4 swine was placed in disposable cartridges and time-varying intensity fluctuations of laser speckle patterns were measured to quantify the viscoelastic modulus during clotting. Coagulation parameters, mainly clotting time, clot progression rate (α-angle and maximum clot stiffness (MA were derived from the clot viscoelasticity trace and compared with standard Thromboelastography (TEG. To demonstrate the capability for anticoagulation sensing in patients, blood samples from 12 patients treated with warfarin anticoagulant were analyzed. LSR clotting time correlated with prothrombin and activated partial thromboplastin time (r = 0.57-0.77, p<0.04 and all LSR parameters demonstrated good correlation with TEG (r = 0.61-0.87, p<0.04. To further evaluate the dose-dependent sensitivity of LSR parameters, swine blood was spiked with varying concentrations of heparin, argatroban and rivaroxaban or serially diluted with saline. We observed that anticoagulant treatments prolonged LSR clotting time in a dose-dependent manner that correlated closely with TEG (r = 0.99, p<0.01. LSR angle was unaltered by anticoagulation whereas TEG angle presented dose-dependent diminution likely linked to the mechanical manipulation of the clot. In both LSR and TEG, MA was largely unaffected by anticoagulation, and LSR presented a higher sensitivity to increased haemodilution in comparison to TEG (p<0.01. Our results establish that LSR rapidly and accurately measures the response of various anticoagulants, opening the opportunity for routine anticoagulation monitoring at the point-of-care or for patient self-testing.

  13. Expression and localization of tissue factor pathway inhibitor-2 in normal and atherosclerotic human vessels

    NARCIS (Netherlands)

    Crawley, James T. B.; Goulding, David A.; Ferreira, Valérie; Severs, Nicholas J.; Lupu, Florea

    2002-01-01

    Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type, serine protease inhibitor with inhibitory activity toward activated factor XI, plasma kallikrein, plasmin, certain matrix metalloproteinases, and the tissue factor:activated factor VII complex. In this study, we investigated TFPI-2

  14. Structural Principles in the Development of Cyclic Peptidic Enzyme Inhibitors

    Science.gov (United States)

    Xu, Peng; Andreasen, Peter A.; Huang, Mingdong

    2017-01-01

    This review summarizes our studies in the development of small cyclic peptides for specifically modulating enzyme activity. Serine proteases share highly similar active sites but perform diverse physiological and pathological functions. From a phage-display peptide library, we isolated two mono-cyclic peptides, upain-1 (CSWRGLENHRMC) and mupain-1 (CPAYSRYLDC), which inhibit the activity of human and murine urokinase-type plasminogen activators (huPA and muPA) with Ki values in the micromolar or sub-micromolar range, respectively. The following affinity maturations significantly enhanced the potencies of the two peptides, 10-fold and >250-fold for upain-1 and mupain-1, respectively. The most potent muPA inhibitor has a potency (Ki = 2 nM) and specificity comparable to mono-clonal antibodies. Furthermore, we also found an unusual feature of mupain-1 that its inhibitory potency can be enhanced by increasing the flexibility, which challenges the traditional viewpoint that higher rigidity leading to higher affinity. Moreover, by changing a few key residues, we converted mupain-1 from a uPA inhibitor to inhibitors of other serine proteases, including plasma kallikrein (PK) and coagulation factor XIa (fXIa). PK and fXIa inhibitors showed Ki values in the low nanomolar range and high specificity. Our studies demonstrate the versatility of small cyclic peptides to engineer inhibitory potency against serine proteases and to provide a new strategy for generating peptide inhibitors of serine proteases. PMID:29104489

  15. Predictive factor and antihypertensive usage of tyrosine kinase inhibitor-induced hypertension in kidney cancer patients

    Science.gov (United States)

    IZUMI, KOUJI; ITAI, SHINGO; TAKAHASHI, YOSHIKO; MAOLAKE, AERKEN; NAMIKI, MIKIO

    2014-01-01

    Hypertension (HT) is the common adverse event associated with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKI). The present study was performed to identify the predictive factors of TKI-induced HT and to determine the classes of antihypertensive agents (AHTA) that demonstrate optimal efficacy against this type of HT. The charts of 50 cases of patients that had received VEGFR-TKI treatment were retrospectively examined. The association between patient background and TKI-induced HT, and the effect of administering AHTA were analyzed. High systolic blood pressure at baseline was identified to be a predictive factor for HT. In addition, there was no difference observed between calcium channel blockers (CCBs) and angiotensin receptor II blockers (ARBs) as first-line AHTA for the control of HT. The findings of the present study may aid with predicting the onset of TKI-induced HT, as well as for its management via the primary use of either CCBs or ARBs. PMID:24959266

  16. An assessment of the utility of unselected coagulation screening in general hospital practice.

    LENUS (Irish Health Repository)

    McHugh, Johnny

    2011-03-01

    Coagulation screening using prothrombin time (PT) and activated partial thromboplastin time (APTT) is widely used. We performed an audit of coagulation screening in an Irish teaching hospital. We analysed PT and\\/or APTT results received during normal working hours during a 1-week period in our hospital. Abnormal results due to anticoagulants were excluded from further study. In samples with PT longer than 15.5 s and\\/or APTT longer than 42 s, we proceeded to 1: 1 mixing studies if the PT was prolonged and 1: 1 mixing studies, factor XII assay and lupus screen if the APTT was prolonged. We also obtained referral source for all samples and clinical details for abnormal samples. Six hundred and seventy-one coagulation requests were received during the study period. Three hundred and eighteen of 671 (47.4%) coagulation requests were for monitoring of anticoagulation. Three hundred and fifty-three of 671 (52.6%) requests were for coagulation screening rather than anticoagulant monitoring. In the coagulation screens received, PT was prolonged in 19 of 353 (5.4%). PT was longer than 20 s in four of 353 cases (1.1%). APTT was prolonged in 19 of 353 (5.4%). APTT was longer than 50 s in four of 353 (1.1%). No patients with abnormal PT or APTT had any bleeding sequelae during the study period. Unregulated coagulation screening has a low yield of abnormal results; the majority of these abnormal results show mild prolongation of PT or APTT with no evidence that they are associated with an increased bleeding risk.

  17. Coagulation, inflammatory, and stress responses in a randomized comparison of open and laparoscopic repair of recurrent inguinal hernia

    DEFF Research Database (Denmark)

    Rahr, H B; Bendix, J; Ahlburg, P

    2006-01-01

    BACKGROUND: In previous comparisons of inflammatory and stress responses to open (OR) and laparoscopic (LR) hernia repair, all operations were performed under general anesthesia. Since local anesthesia is widely used for OR, a comparison of this approach with LR seemed relevant. METHODS: Patients...... with recurrent inguinal hernia were randomized to OR under local anesthesia (n = 30) or LR under general anesthesia (n = 31). The magnitude of the surgical trauma was assessed by measuring markers of coagulation (prothrombin fragment 1 + 2), endothelial activation (von Willebrand factor), inflammation...... [leukocytes, interleukin-6, -8 and -10, granulocyte macrophage colony-stimulating factor, and C-reactive protein (CRP)], and endocrine stress (cortisol) in blood collected before operation, 4 h postincision, and on postoperative day 2. RESULTS: Leukocyte counts and interleukin-6 and CRP levels increased...

  18. Effect of intravenous administration of dextrose on coagulation in healthy dogs.

    Science.gov (United States)

    Gonzales, Jennifer L; Hanel, Rita M; Hansen, Bernie D; Marks, Steve L

    2011-04-01

    To investigate effects of IV administration of dextrose on coagulation in healthy dogs. 7 dogs. Thromboelastography and coagulation panel analysis were used to assess coagulation. Samples (S1 through S9) were collected during the study phases: phase 0 (S1 [baseline]); phase 1 (S2 and S3), infusion of crystalloid fluid without dextrose; phase 2 (S4 and S5), high-rate dextrose infusion; phase 3 (S6, S7, and S8), moderate-rate dextrose infusion; and phase 4 (S9), discontinuation of fluids for 24 hours. In phase 3, dogs were allocated to 2 groups; 1 was administered dextrose at a rate comparable to total parental nutrition (40% of resting energy requirement; group A), and 1 was administered dextrose at rates equaling 70% to 90% of resting energy requirement (group B). Blood glucose concentration was measured every 2 hours. No dogs had clinically relevant sustained hyperglycemia. Maximum amplitude and elastic shear modulus were significantly lower at S6 than at S1 through S4. Concentration of D-dimer was significantly higher at S6 than at S1, S3, and S4 and significantly higher at S5 than at S3. Prothrombin time was significantly prolonged at S3, S5, S7, S8, and S9, compared with the value at S1. Activated partial thromboplastin time was significantly prolonged at S5 and S6, compared with values at S1, S2, S3, S4, and S9. IV administration of dextrose to healthy dogs at rates comparable to or higher than those for conventional parenteral nutrition resulted in mild but clinically unimportant interference with coagulation.

  19. Non-genetic risk factors in haemophilia A inhibitor management

    DEFF Research Database (Denmark)

    Löfgren, Karin Maria; Søndergaard, H.; Skov, Søren

    2016-01-01

    In haemophilia A (HA) management, antidrug antibodies, or inhibitors, are a serious complication that renders factor VIII (FVIII) replacement therapy ineffective, increases morbidity and reduces quality of life for affected patients. Inhibitor development aetiology is multifactorial and covers both...... stressed, injured or dying cells can activate an immune reaction, without the involvement of foreign antigens. Bleeds, trauma, surgery or concomitant infection could be events initiating danger signalling in HA patients, resulting in an immune reaction towards administered FVIII that otherwise would pass...

  20. Monoclonal antibodies to human factor VII: a one step immunoradiometric assay for VII:Ag.

    OpenAIRE

    Takase, T; Tuddenham, E G; Chand, S; Goodall, A H

    1988-01-01

    Three mouse monoclonal antibodies (RFF-VII/1, RFF-VII/2, and RFF-VII/3) which bind specifically to different epitopes on human factor VII antigen were raised. Two of the antibodies, RFF-VII/1 and RFF-VII/2, bound strongly to factor VII antigen (VII:Ag), but only RFF-VII/1 and RFF-VII/3 were potent inhibitors of factor VII coagulation activity (VII:C). RFF-VII/1 and RFF-VII/2 were used in a one step, double monoclonal immunoradiometric assay for VII:Ag. This was highly reproducible and detecte...

  1. Pathogen reduction of blood components.

    Science.gov (United States)

    Solheim, Bjarte G

    2008-08-01

    Thanks to many blood safety interventions introduced in developed countries the risk of transfusion transmitted infections has become exceedingly small in these countries. However, emerging pathogens still represent a serious challenge, as demonstrated by West Nile virus in the US and more recently by Chikungunya virus in the Indian Ocean. In addition bacterial contamination, particularly in platelets, and protozoa transmitted by blood components still represent sizeable risks in developed countries. In developing countries the risk of all transfusion transmitted infections is still high due to insufficient funding and organisation of the health service. Pathogen reduction of pooled plasma products has virtually eliminated the risk of transfusion transmitted infections, without compromising the quality of the products significantly. Pathogen reduction of blood components has been much more challenging. Solvent detergent treatment which has been so successfully applied for plasma products dissolves cell membranes, and can, therefore, only be applied for plasma and not for cellular blood components. Targeting of nucleic acids has been another method for pathogen inactivation of plasma and the only approach possible for cellular blood products. As documented in more than 15 year's track record, solvent detergent treatment of pooled plasma can yield high quality plasma. The increased risk for contamination by unknown viruses due to pooling is out weighed by elimination of TRALI, significant reduction in allergic reactions and standardisation of the product. Recently, a promising method for solvent detergent treatment of single donor plasma units has been published. Methylene blue light treatment of single donor plasma units has a similar long track record as pooled solvent detergent treated plasma; but the method is less well documented and affects coagulation factor activity more. Psoralen light treated plasma has only recently been introduced (CE marked in Europe

  2. Mechanisms behind efficacy of tumor necrosis factor inhibitors in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Olesen, Caroline Meyer; Coskun, Mehmet; Peyrin-Biroulet, Laurent

    2016-01-01

    Biological treatment with tumor necrosis factor (TNF) inhibitors is successful in the management of inflammatory bowel disease (IBD). All TNF inhibitors antagonize the pro-inflammatory cytokine TNF-α but with varying efficacies in IBD. The variations in efficacy probably are caused by structural ...... inhibitors in order to identify mechanisms of importance for their efficacy in IBD. Thus, a better understanding of the mechanistic basis for clinical efficacy can lead to a more rational use of TNF inhibitors in the management of IBD....

  3. PEGylated DX-1000: Pharmacokinetics and Antineoplastic Activity of a Specific Plasmin Inhibitor

    Directory of Open Access Journals (Sweden)

    Laetitia Devy

    2007-11-01

    Full Text Available Novel inhibitors of the urokinase-mediated plasminogen (plg activation system are potentially of great clinical benefit as anticancer treatments. Using phage display, we identified DX-1000 a tissue factor pathway inhibitor-derived Kunitz domain protein which is a specific high-affinity inhibitor of plasmin (pin (Ki = 99 pM. When tested in vitro, DX-1000 blocks plasminmediated pro-matrix metal loproteinase-9 (proMMP-9 activation on cells and dose-dependently inhibits tube formation, while not significantly affecting hemostasis and coagulation. However, this low-molecular weight protein inhibitor (~ 7 kDa exhibits rapid plasma clearance in mice and rabbits, limiting its potential clinical use in chronic diseases. After site-specific PEGylation, DX-1000 retains its activity and exhibits a decreased plasma clearance. This PEGylated derivative is effective in vitro, as well as potent in inhibiting tumor growth of green fluorescent protein (GFP-labeled MDA-MB-231 cells. 4PEG-DX-1000 treatment causes a significant reduction of urokinase-type plasminogen activator (uPA and plasminogen expressions, a reduction of tumor proliferation, and vascularization. 4PEG-DX-1000 treatment significantly decreases the level of active mitogenactivated protein kinase (MAPK in the primary tumors and reduces metastasis incidence. Together, our results demonstrate the potential value of plasmin inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.

  4. Development and characterization of recombinant ovine coagulation factor VIII.

    Directory of Open Access Journals (Sweden)

    Philip M Zakas

    Full Text Available Animal models of the bleeding disorder, hemophilia A, have been an integral component of the biopharmaceutical development process and have facilitated the development of recombinant coagulation factor VIII (fVIII products capable of restoring median survival of persons with hemophilia A to that of the general population. However, there remain several limitations to recombinant fVIII as a biotherapeutic, including invasiveness of intravenous infusion, short half-life, immunogenicity, and lack of availability to the majority of the world's population. The recently described ovine model of hemophilia A is the largest and most accurate phenocopy. Affected sheep die prematurely due to bleeding-related pathogenesis and display robust adaptive humoral immunity to non-ovine fVIII. Herein, we describe the development and characterization of recombinant ovine fVIII (ofVIII to support further the utility of the ovine hemophilia A model. Full-length and B-domain deleted (BDD ofVIII cDNAs were generated and demonstrated to facilitate greater biosynthetic rates than their human fVIII counterparts while both BDD constructs showed greater expression rates than the same-species full-length versions. A top recombinant BDD ofVIII producing baby hamster kidney clone was identified and used to biosynthesize raw material for purification and biochemical characterization. Highly purified recombinant BDD ofVIII preparations possess a specific activity nearly 2-fold higher than recombinant BDD human fVIII and display a differential glycosylation pattern. However, binding to the carrier protein, von Willebrand factor, which is critical for stability of fVIII in circulation, is indistinguishable. Decay of thrombin-activated ofVIIIa is 2-fold slower than human fVIII indicating greater intrinsic stability. Furthermore, intravenous administration of ofVIII effectively reverses the bleeding phenotype in the murine model of hemophilia A. Recombinant ofVIII should facilitate

  5. Potent, selective, orally bioavailable inhibitors of tumor necrosis factor-alpha converting enzyme (TACE): discovery of indole, benzofuran, imidazopyridine and pyrazolopyridine P1' substituents.

    Science.gov (United States)

    Lu, Zhonghui; Ott, Gregory R; Anand, Rajan; Liu, Rui-Qin; Covington, Maryanne B; Vaddi, Krishna; Qian, Mingxin; Newton, Robert C; Christ, David D; Trzaskos, James; Duan, James J-W

    2008-03-15

    Potent and selective inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) were discovered with several new heterocyclic P1' groups in conjunction with cyclic beta-amino hydroxamic acid scaffolds. Among them, the pyrazolopyridine provided the best overall profile when combined with tetrahydropyran beta-amino hydroxamic acid scaffold. Specifically, inhibitor 49 showed IC(50) value of 1 nM against porcine TACE and 170 nM in the suppression of LPS-induced TNF-alpha of human whole blood. Compound 49 also displayed excellent selectivity over a wide panel of MMPs as well as excellent oral bioavailability (F%>90%) in rat n-in-1 PK studies.

  6. [Whole-blood transfusion for hemorrhagic shock resuscitation: two cases in Djibouti].

    Science.gov (United States)

    Cordier, P Y; Eve, O; Dehan, C; Topin, F; Menguy, P; Bertani, A; Massoure, P L; Kaiser, E

    2012-01-01

    Hemorrhagic shock requires early aggressive treatment, including transfusion of packed red blood cells and hemostatic resuscitation. In austere environments, when component therapy is not available, warm fresh whole-blood transfusion is a convenient treatment. It provides red blood cells, clotting factors, and functional platelets. Therefore it is commonly used in military practice to treat hemorrhagic shock in combat casualties. At Bouffard Hospital Center in Djibouti, the supply of packed red blood cells is limited, and apheresis platelets are unavailable. We used whole blood transfusion in two civilian patients with life-threatening non-traumatic hemorrhages. One had massive bleeding caused by disseminated intravascular coagulation due to septic shock; the second was a 39 year-old pregnant woman with uterine rupture. In both cases, whole blood transfusion (twelve and ten 500 mL bags respectively), combined with etiological treatment, enabled coagulopathy correction, hemorrhage control, and satisfactory recovery.

  7. Hypomethylation of serum blood clot DNA, but not plasma EDTA-blood cell pellet DNA, from vitamin B12-deficient subjects.

    Directory of Open Access Journals (Sweden)

    Eoin P Quinlivan

    Full Text Available Vitamin B12, a co-factor in methyl-group transfer, is important in maintaining DNA (deoxycytidine methylation. Using two independent assays we examined the effect of vitamin B12-deficiency (plasma vitamin B12<148 pmol/L on DNA methylation in women of childbearing age. Coagulated blood clot DNA from vitamin B12-deficient women had significantly (p<0.001 lower percentage deoxycytidine methylation (3.23±0.66%; n = 248 and greater [3 H]methyl-acceptance (42,859±9,699 cpm; n = 17 than DNA from B12-replete women (4.44±0.18%; n = 128 and 26,049±2,814 cpm; n = 11 [correlation between assays: r = -0.8538; p<0.001; n = 28]. In contrast, uncoagulated EDTA-blood cell pellet DNA from vitamin B12-deficient and B12-replete women exhibited similar percentage methylation (4.45±0.15%; n = 77 vs. 4.47±0.15%; n = 47 and [3 H]methyl-acceptance (27,378±4,094 cpm; n = 17 vs. 26,610±2,292 cpm; n = 11. Therefore, in simultaneously collected paired blood samples, vitamin B12-deficiency was associated with decreased DNA methylation only in coagulated samples. These findings highlight the importance of sample collection methods in epigenetic studies, and the potential impact biological processes can have on DNA methylation during collection.

  8. Hemodilution on Cardiopulmonary Bypass: Thromboelastography Patterns and Coagulation-Related Outcomes.

    Science.gov (United States)

    Ranucci, Marco; Baryshnikova, Ekaterina; Ciotti, Erika; Ranucci, Matteo; Silvetti, Simona

    2017-10-01

    Hemodilution has been associated with both hypocoagulability and hypercoagulability in studies based on thromboelastography (TEG). Severe hemodilution during cardiopulmonary bypass (CPB) is a risk factor for morbidity in cardiac surgery. This study investigated the effects of different degrees of hemodilution with CPB on post-CPB TEG parameters and coagulation-related outcomes. Retrospective cohort study. University research hospital. The study comprised 793 cardiac surgery patients. None. The patient population was divided into low (LH), moderate (MH), and severe (SH) hemodilution groups based on the hemodilution degree on CPB. Differences in TEG parameters and coagulation-related outcomes were assessed. Patients with SH experienced significantly (p = 0.019) prolonged clotting times (median r-time 6.1 min, interquartile range 5.1-7.4 min) with respect to patients with MH (median r-time 5.8 min, interquartile range 4.8-7 min) and LH (median r-time 5.9 min, interquartile range 4.8-7.2 min). Clot firmness was significantly (p = 0.001) lower in patients with SH (median maximum amplitude 63 mm, interquartile range 57-68 mm) compared with patients with MH (median maximum amplitude 65 mm, interquartile range 61-71 mm) and LH (median maximum amplitude 67 mm, interquartile range 62-74 mm). Patients with SH had higher chest drain blood loss and required more fresh frozen plasma and platelet concentrate transfusions than did patients with MH or LH. Postoperative thromboembolic complications were significantly (p = 0.006) more common in patients with SH (2.6%) than in patients with MH (0%) or LH (0.4%). SH on CPB is associated with hypocoagulation, bleeding, and thrombosis-associated worse outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Role of Factor Xa Inhibitors in Cancer-Associated Thrombosis: Any New Data?

    Directory of Open Access Journals (Sweden)

    Ali Zalpour

    2011-01-01

    Full Text Available The association between cancer and venous thromboembolism (VTE has been well documented in the literature. Prevention and treatment of VTE in cancer patients is imperative. Typically, the mainstay regimen for VTE prevention and treatment has been anticoagulation therapy, unless contraindicated. This therapy consists of unfractionated heparin (UFH, low-molecular-weight heparin (LMWH, factor Xa inhibitor, or vitamin K antagonist (VKA. Current guidelines recommend LMWH over VKA for the treatment of VTE in cancer patients. Factor-specific anticoagulants have been proven safe and effective, and recently factor Xa inhibitors have emerged as a treatment alternative to heparins and VKA. Currently, three factor Xa inhibitors have been identified: fondaparinux (the only one approved so far by the US Food and Drug Administration, idraparinux (in clinical trials, and idrabiotaparinux (in clinical trials. This paper will examine the role of these agents, focusing on fondaparinux, for the prevention and treatment of VTE in cancer patients.

  10. Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of pulmonary embolism.

    Science.gov (United States)

    Robertson, Lindsay; Kesteven, Patrick; McCaslin, James E

    2015-12-04

    Pulmonary embolism is a potentially life-threatening condition in which a clot can travel from the deep veins, most commonly in the leg, up to the lungs. Previously, a pulmonary embolism was treated with the anticoagulants heparin and vitamin K antagonists. Recently, however, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the long-term treatment (minimum duration of three months) of pulmonary embolism. To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the long-term treatment of pulmonary embolism. The Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). Clinical trials databases were also searched for details of ongoing or unpublished studies. We searched the reference lists of relevant articles retrieved by electronic searches for additional citations. We included randomised controlled trials in which patients with a pulmonary embolism confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor for the long-term (minimum duration three months) treatment of pulmonary embolism. Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third author (PK). We used meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent venous thromboembolism and pulmonary embolism. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes

  11. Inhibitors in haemophilia A: a perspective on clotting factor products as a potential contributing factor.

    Science.gov (United States)

    Mathew, P; Dinter, H; Church, N; Humphries, T J; Kulkarni, R

    2016-05-01

    The occurrence of a neutralizing antibody in previously untreated patients (PUPs) with haemophilia A appears to be the result of an intricate interplay of both genetic and environmental factors. Recently, the type of factor VIII (FVIII) product used in the PUPs population has been implicated as a risk factor for inhibitor development. The aim of this review was to explore in a systematic manner potential hypotheses for the product-related findings in these studies (i.e. differences in the expression system of the cell lines used to produce recombinant FVIII [rFVIII], differences in the administered antigen load or changes in clinical practice over time). Review of the available clinical studies illustrates the high degree of variability for the risk of inhibitor development for the same products across different studies. Differences in cell lines or antigen load were not found to provide a reasonable explanation. The possibility of changes in clinical practice over time and patient selection bias (i.e. the preferential use of one product over another in patients at higher risk for inhibitors) offers a potential explanation and should be carefully considered when evaluating the studies. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  12. Multiple response optimization of the coagulation process for upgrading the quality of effluent from municipal wastewater treatment plant

    Science.gov (United States)

    Li, Na; Hu, Yi; Lu, Yong-Ze; Zeng, Raymond J.; Sheng, Guo-Ping

    2016-05-01

    To meet the high quality standard of receiving water, the coagulation process using polyferric chloride (PFC) was used to further improve the water quality of effluent from wastewater treatment plants. Uniform design (UD) coupled with response surface methodology (RSM) was adopted to assess the effects of the main influence factors: coagulant dosage, pH and basicity, on the removal of total organic carbon (TOC), NH4+-N and PO43--P. A desirability function approach was used to effectively optimize the coagulation process for the comprehensive removal of TOC, NH4+-N and PO43--P to upgrade the effluent quality in practical application. The optimized operating conditions were: dosage 28 mg/L, pH 8.5 and basicity 0.001. The corresponding removal efficiencies for TOC, NH4+-N and PO43--P were 77.2%, 94.6% and 20.8%, respectively. More importantly, the effluent quality could upgrade to surface water Class V of China through coagulation under optimal region. In addition, grey relational analysis (GRA) prioritized these three factors as: pH > basicity > dosage (for TOC), basicity > dosage > pH (for NH4+-N), pH > dosage > basicity (for PO43--P), which would help identify the most important factor to control the treatment efficiency of various effluent quality indexes by PFC coagulation.

  13. The Assessment of Radioactive Liquid Waste Treatment Generated From The Fuel Reprocessing Plant Using Chemical Coagulation Method

    International Nuclear Information System (INIS)

    Kuncoro Arief, H; M Birmano, Dj

    1998-01-01

    Reprocessing of nuclear spent fuel produced 8 lot of radioactive liquid waste still bearing uranium and transuranium. The assessment of the radioactive liquid waste treatment with FeCI 3 as coagulant has been done. Decontamination factor and separation efficiency can be calculated from known activities of initial and post-treatment wastes. It can be concluded that some factors i.e. pH of treatment process, quantity of coagulant, mixing rate, and mixing time have influenced the treatment product

  14. Effect of ABO blood type on the outcomes of patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors.

    Science.gov (United States)

    Omae, Kenji; Fukuma, Shingo; Ikenoue, Tatsuyoshi; Kondo, Tsunenori; Takagi, Toshio; Ishihara, Hiroki; Tanabe, Kazunari; Fukuhara, Shunichi

    2017-09-01

    To assess the effect of blood type on survival outcomes and adverse events (AEs) in patients treated with tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). Patients who received TKIs as first-line therapy for mRCC between 2008 and 2015 at our hospital were included in the study (n = 136). Patients were divided into 2 groups based on their blood type as O and non-O. Survival outcomes and AEs were compared according to blood type. Cox regression models were used for univariate and multivariate survival analyses. Of the 136 patients, 34 (25%) and 102 (75%) had O and non-O blood types, respectively. Blood type O was associated with an increased number of disease sites. There were no differences between the 2 groups with respect to other baseline characteristics. The progression-free survival in patients with O and non-O blood types was 12.1 and 11.6 months, respectively; the overall survival was 34.4 and 24.8 months, respectively. On univariate and multivariate analyses, the ABO blood type was not a significant prognostic factor for progression-free survival or overall survival. Furthermore, the incidences of serious AEs were similar in the 2 blood groups. ABO blood type was not associated with survival outcomes or incidences of serious AEs in mRCC patients treated with TKIs. However, blood type O may be associated with an increased number of disease sites. Copyright © 2017. Published by Elsevier Inc.

  15. Comparison of Moringa stenopetala seed extract as a clean coagulant with Alum and Moringa stenopetala-Alum hybrid coagulant to remove direct dye from Textile Wastewater.

    Science.gov (United States)

    Dalvand, Arash; Gholibegloo, Elham; Ganjali, Mohammad Reza; Golchinpoor, Najmeh; Khazaei, Mohammad; Kamani, Hossein; Hosseini, Sara Sadat; Mahvi, Amir Hossein

    2016-08-01

    In this study, the efficiency of Moringa stenopetala seed extract was compared with alum and M. stenopetala-alum hybrid coagulant to remove Direct Red 23 azo dye from textile wastewater. The effects of parameters such as pH, coagulant dose, type of salt used for the extraction of coagulant and initial dye concentration on dye removal efficiency were investigated. Moreover, the existing functional groups on the structure of M. stenopetala coagulant (MSC) were determined by Fourier transform infrared spectroscopy, and the morphology of sludge produced by MSC, alum, and hybrid coagulant was characterized by scanning electron microscopy. Ninhydrin test was also used to determine the quantity of primary amines in the MSC and Moringa oleifera coagulant (MOC). According to the results, with increasing the coagulant dose and decreasing the initial dye concentration, dye removal efficiency has increased. The maximum dye removal of 98.5, 98.2, and 98.3 % were obtained by using 240, 120, and 80 mg/L MSC, alum and hybrid coagulant at pH 7, respectively. The results also showed MSC was much more effective than MOC for dye removal. The volume of sludge produced by MSC was one fourth and half of those produced by alum and hybrid coagulant, respectively. Based on the results, hybrid coagulant was the most efficient coagulant for direct dye removal from colored wastewater.

  16. Novel HIT antibody detection method using Sonoclot® coagulation analyzer.

    Science.gov (United States)

    Wanaka, Keiko; Asada, Reiko; Miyashita, Kumiko; Kaneko, Makoto; Endo, Hirokazu; Yatomi, Yutaka

    2015-01-01

    Since heparin-induced thrombocytopenia (HIT), caused by the generation of antibodies against platelet factor 4 (PF4)/heparin complexes (HIT antibodies), may induce serious complications due to thrombosis, a prompt diagnosis is desirable. Functional tests with platelet activation to detect HIT antibodies are useful for diagnosis of HIT, in particular (14)C-selotonin release assay (SRA). However, they are complicated and so can be performed only in limited laboratories. We tested if a blood coagulation test using Sonoclot® analyzer can serve for the detection of HIT antibodies. A murine monoclonal antibody (HIT-MoAb) against PF4/heparin complexes was used as an alternative to human HIT antibodies. To the mixture of HIT-MoAb and heparin (0.5 U/mL, final), whole blood obtained from a healthy volunteer was added, and then the activated clotting time (ACT), clot rate (CR), and area under the curve (AUC) were measured with Sonoclot® analyzer for 30minutes. The HIT-MoAb (30 to 100μg/mL, final) concentration dependently suppressed the anticoagulation activity (prolongation of ACT and decrease of CR and AUC) of heparin. The suppression of anticoagulation effect of heparin by HIT-MoAb was demonstrated by measurements using Sonoclot® analyzer. This method may provide a new tool for screening of HIT antibodies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

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    Cimino E

    2014-12-01

    Full Text Available Ernesto Cimino,1 Silvia Linari,2 Mara Malerba,3 Susan Halimeh,4 Francesca Biondo,5 Martina Westfeld5 1Dipartimento Medicina Clinica e Sperimentale, Universita’ degli Studi di Napoli Federico II, Naples, Italy; 2Agenzia per l’ Emofilia, AOU Careggi di Firenze, Florence, Italy; 3Fondazione Cà Granda Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi “A Bianchi Bonomi”, Milan, Italy; 4CRC Coagulation Research Centre GmbH, Duisburg, Germany; 5Pfizer Italia, Rome, Italy Introduction: Hemophilia A treatment involves replacing the deficient coagulation factor VIII. This process may involve multiple steps that might create a barrier to adherence. A new dual-chamber syringe (DCS; FuseNGo® was recently introduced with the aim of simplifying reconstitution. Aim: This study aimed to identify factors associated with adult patients’ preferences for different coagulation factor VIII reconstitution systems and to test ease of use and patient preference for the DCS. Methods: A cross-sectional survey of adults with hemophilia A in five European countries was conducted; a subset of subjects also participated in a practical testing session of the DCS. Results: Among the 299 survey participants, the device scenario requiring the least equipment and reconstitution steps (the DCS received a median preference rating of 71 out of 100 (0 being “the least desirable” and 100 “the most desirable” rating. This was significantly higher than the other scenarios (the next highest achieved a median of 50 points; P<0.001. Participants would be more likely to use this device prophylactically (P<0.001. Among the 98 participants who tested the DCS, 57% preferred this device over their current device, 26% preferred their current device, and 17% had no preference. The DCS was rated as easier to use than current treatment devices (median score 9/10 versus 7/10 for current treatment, P=0.001. Conclusion: The survey indicates that the prefilled DCS, Fuse

  18. [Internal quality control of the blood products in the Lomé National Blood Transfusion Centre].

    Science.gov (United States)

    Fétéké, L; Mawussi, K; Lakté, P; Kuéviakoe, I M; Haudrechy, D; Ségbéna, A Y

    2008-07-01

    Evaluate the conformity of blood red cells units prepared in the Lomé CNTS with European norms concerning volume, haemoglobin content and haematocrite. Measure the conservation of the haemostatic properties and the rate of haemostasis factors V and VIII in the fresh frozen plasma. Measure the rate of residual cells in the plasma. In the year 2006, from March 1st to April 15th, we analysed the quality of 135 units of whole blood, red blood cells (RBC) and plasma from blood donors in the Lomé National Blood Transfusion Centre. The quality control had concerned: the volume of whole blood units; the volume, the haemoglobin content and the haematocrite of red blood cells units; the volume, the prothrombin rate, the cephalin with activator time (TCA), the rate of haemostasis factors V and VIII and the number of residual cells (red cells, leucocytes and platelets) in the plasma. Among the 135 units of whole blood which were controlled, 50.57% were in conformity with the norms concerning the volume. The red blood cells units were in conformity with norms concerning their volume, their haemoglobin content and their haematocrite respectively in 21.48%, 80.75% and 20% of the cases. The volume of 75.56% of the plasma units controlled were conform with the norm. All of the plasma units were conform with the norm concerning the number of residual platelets while the number of residual red blood cells and leucocytes were conform respectively in 80.74% and 60%. The percentage of conformity concerning the prothrombin rate, the TCA, the coagulation factor V and the factor VIII were respectively 66.67; 97.78; 48.89 and 47.4 before freezing, and 54.81; 88.14; 64.44; 84.44 a month after freezing. To improve the quality of the new blood products of the Lomé CNTS, some correctives actions must be applied concerning the adequate volume of blood which must be collected from the donors, the position of the blood bags in during the centrifugation and the volume of plasma which must be

  19. Effects of Dipeptidyl Peptidase-4 Inhibitors on Hyperglycemia and Blood Cyclosporine Levels in Renal Transplant Patients with Diabetes: A Pilot Study

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    Jaehyun Bae

    2016-03-01

    Full Text Available BackgroundThe use of dipeptidyl peptidase-4 (DPP-4 inhibitors is increasing among renal transplant patients with diabetes. However, the glucose-lowering efficacies of various DPP-4 inhibitors and their effects on blood cyclosporine levels have not been fully investigated. We compared the glucose-lowering efficacies of DPP 4 inhibitors and evaluate their effects on the blood levels of cyclosporine in renal transplant recipients with diabetes.MethodsSixty-five renal allograft recipients who received treatment with DPP-4 inhibitors (vildagliptin, sitagliptin, or linagliptin following kidney transplant were enrolled. The glucose-lowering efficacies of the DPP-4 inhibitors were compared according to the changes in the hemoglobin A1c (HbA1c levels after 3 months of treatment. Changes in the trough levels of the cyclosporine were also assessed 2 months after treatment with each DPP-4 inhibitor.ResultsHbA1c significantly decreased in the linagliptin group in comparison with other DPP-4 inhibitors (vildagliptin –0.38%±1.03%, sitagliptin –0.53%±0.95%, and linagliptin –1.40±1.34; P=0.016. Cyclosporine trough levels were significantly increased in the sitagliptin group compared with vildagliptin group (30.62±81.70 ng/mL vs. –24.22±53.54 ng/mL, P=0.036. Cyclosporine trough levels were minimally changed in patients with linagliptin.ConclusionLinagliptin demonstrates superior glucose-lowering efficacy and minimal effect on cyclosporine trough levels in comparison with other DPP-4 inhibitors in kidney transplant patients with diabetes.

  20. A novel serpin with antithrombin-like activity in Branchiostoma japonicum: implications for the presence of a primitive coagulation system.

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    Yeqing Chao

    Full Text Available Serine protease inhibitors, or serpins, are a group of widely distributed proteins with similar structures that use conformational change to inhibit proteases. Antithrombin (AT is a member of the serine protease inhibitor superfamily and a major coagulation inhibitor in all vertebrates, but its evolutionary origin remains elusive. In this study we isolated for the first time a cDNA encoding an antithrombin homolog, BjATl, from the protochordate Branchiostoma japonicum. The deduced protein BjATl consisted of 338 amino acids sharing 36.7% to 41.1% identity to known vertebrate ATs. BjATl contains a potential N-linked glycosylation site, two potential heparin binding sites and the reactive center loop with the absolutely conserved sequence Gly-Arg-Ser; all of these are features characteristic of ATs. All three phylogenetic trees constructed using Neighbor-Joining, Maximum-Likelihood and Bayesian-Inference methods also placed BjATl together with ATs. Moreover, BjATl expressed in yeast cells was able to inhibit bovine thrombin activity by forming a SDS-stable BjATl-thrombin complex. It also displays a concentration-dependent inhibition of thrombin that is accelerated by heparin. Furthermore, BjATl was predominantly expressed in the hepatic caecum and hind-gut, agreeing with the expression pattern of AT in mammalian species. All these data clearly demonstrate that BjATl is an ortholog of vertebrate ATs, suggesting that a primitive coagulation system emerged in the protochordate.