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Sample records for blood coagulation factor inhibitors

  1. 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...

  2. Blood coagulation factor VIII: An overview

    Indian Academy of Sciences (India)

    G M Bhopale; R K Nanda

    2003-12-01

    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 clinician should be interested.

  3. Tissue Factor, Blood Coagulation, and Beyond: An Overview

    Directory of Open Access Journals (Sweden)

    Arthur J. Chu

    2011-01-01

    Full Text Available Emerging evidence shows a broad spectrum of biological functions of tissue factor (TF. TF classical role in initiating the extrinsic blood coagulation and its direct thrombotic action in close relation to cardiovascular risks have long been established. TF overexpression/hypercoagulability often observed in many clinical conditions certainly expands its role in proinflammation, diabetes, obesity, cardiovascular diseases, angiogenesis, tumor metastasis, wound repairs, embryonic development, cell adhesion/migration, innate immunity, infection, pregnancy loss, and many others. This paper broadly covers seminal observations to discuss TF pathogenic roles in relation to diverse disease development or manifestation. Biochemically, extracellular TF signaling interfaced through protease-activated receptors (PARs elicits cellular activation and inflammatory responses. TF diverse biological roles are associated with either coagulation-dependent or noncoagulation-mediated actions. Apparently, TF hypercoagulability refuels a coagulation-inflammation-thrombosis circuit in “autocrine” or “paracrine” fashions, which triggers a wide spectrum of pathophysiology. Accordingly, TF suppression, anticoagulation, PAR blockade, or general anti-inflammation offers an array of therapeutical benefits for easing diverse pathological conditions.

  4. Coagulation inhibitors in inflammation.

    Science.gov (United States)

    Esmon, C T

    2005-04-01

    Coagulation is triggered by inflammatory mediators in a number of ways. However, to prevent unwanted clot formation, several natural anticoagulant mechanisms exist, such as the antithrombin-heparin mechanism, the tissue factor pathway inhibitor mechanism and the protein C anticoagulant pathway. This review examines the ways in which these pathways are down-regulated by inflammation, thus limiting clot formation and decreasing the natural anti-inflammatory mechanisms that these pathways possess. PMID:15787615

  5. Blood coagulation factor Xa as an emerging drug target

    NARCIS (Netherlands)

    K. Borensztajn; C.A. Spek

    2011-01-01

    Introduction: Factor (F) Xa is well-known as an important player in the coagulation cascade responsible for thrombin generation. More recently, FXa emerged as an essential player in cell biology via activation of proteaseactivated receptors (PAR)-1 and -2. This pleiotropic role of FXa forms the basi

  6. ACTION OF HIGH-DISPERSED SILICA ON BLOOD COAGULATION FACTORS ACTIVATION

    Directory of Open Access Journals (Sweden)

    T. M. Chernyshenko

    2013-02-01

    Full Text Available Using of high-dispersed silica based sorbents is a new and prospective method of bleeding arrest. Studies of high-dispersed silica haemostatic action during superficial wounds were promising for its surgery usage. However the mechanisms of haemostatic effects of high-dispersed silica are still unknown. Our investigations were focused on high-dispersed silica action on activation of some blood coagulation factors and clearing of its blood arresting mechanisms. Activation of individual coagulation factors was measured using specific chromogenic substrates. It was shown that high-dispersed silica increases the activation of intrinsic and extrinsic blood coagulation pathway factors which was initiated by «Activated partial thromboplastin time» and thromboplastin. Blood coagulation factor X was determined as a target of high-dispersed silica using highspecific activators from the snake venoms. Observed increasing of factor X activation could be the consequence of the adsorption of the intrinsic blood coagulation pathway factors on sorbent surface. Obtained results give a possibility to speculate about high-dispersed silica effects on blood coagulation increasing.

  7. Change of Coagulation Factor Ⅷ and Antithrombin Ⅲ Activity in Bank-Stored Blood

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Coagulation factor Ⅷ and antithrombin Ⅲ activity were detected in 15 health donors. It was found that antithrombin Ⅲ activity decreased obviously 12 h after blood drawing. It lost 56 % of the activity at the 3rd day, and 70 % of the activity at the 7th day. FⅧ:c showed no obvious change after 24 h, until the 3rd day. It lost 40 %-60 % of the activity after 36 h and was reduced to the 30 % of the original activity at the 5th day. Our results suggested that at the 3rd day coagulation factor Ⅷ of bank-stored blood can be used to replenish antithrombin Ⅲ, while bank-stored blood in one day can be used to replenish FⅧ.

  8. 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...

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

    Science.gov (United States)

    Puy, Cristina; Tucker, Erik I.; Ivanov, Ivan S.; Gailani, David; Smith, Stephanie A.; Morrissey, James H.; Gruber, András; McCarty, Owen J. T.

    2016-01-01

    Introduction 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. Methods and Results 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. Conclusions 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. PMID:27764259

  10. Coagulation Factor and Hemostatic Protein Content of Canine Plasma after Storage of Whole Blood at Ambient Temperature

    OpenAIRE

    Walton, J.E.; Hale, A. S.; Brooks, M. B.; Boag, A.K.; Barnett, W.; Dean, R.

    2014-01-01

    Background Standard practice in canine blood banking is to produce fresh frozen plasma (FFP) by separating and freezing plasma produced from blood within 8 hours of collection. Within canine blood donation programs, this can limit the number of units collected. Hypothesis/Objectives The aim was to compare the coagulation factor and hemostatic protein content (CF&HPC) of plasma produced from blood stored at ambient temperature for 8, 12, and 24 hours. Another aim was to compare the CF&HPC betw...

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

    International Nuclear Information System (INIS)

    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 125I-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

  12. Antithrombin, an Important Inhibitor in Blood Clots.

    Science.gov (United States)

    Zhu, Ying; Cong, Qing-Wei; Liu, Yue; Wan, Chun-Ling; Yu, Tao; He, Guang; He, Lin; Cai, Lei; Chou, Kuo-Chen

    2016-01-01

    Blood coagulation is healthy and lifesaving because it can stop bleeding. It can, however, be a troublemaker as well, causing serious medical problems including heart attack and stroke. Body has complex blood coagulation cascade to modulate the blood clots. In the environment of plasma, the blood coagulation cascade is regulated by antithrombin, which is deemed one of the most important serine protease inhibitors. It inhibits thrombin; it can inhibit factors IXa and Xa as well. Interestingly, its inhibitory ability will be significantly increased with the existence of heparin. In this minireview paper, we are to summarize the structural features of antithrombin, as well as its heparin binding modes and anti-coagulation mechanisms, in hopes that the discussion and analysis presented in this paper can stimulate new strategies to find more effective approaches or compounds to modulate the antithrombin. PMID:26411319

  13. Mathematical Model of Extrinsic Blood Coagulation Cascade Dynamic System

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The blood coagulation system is very important to life. This paper presents a mathematical blood coagulation model for the extrinsic pathway. This model simulates clotting factor VIII, which plays an important role in the coagulation mechanism. The mathematical model is used to study the equilibrium stability, orbit structure, attractors and global stability behavior, with conclusions in accordance with the physiological phenomena. Moreover, the results provide information about blood related illnesses, which can be used for further study of the coagulation mechanism.

  14. [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.

  15. Advances in coagulation factor Xa inhibitor%凝血因子Xa抑制药研究进展

    Institute of Scientific and Technical Information of China (English)

    黄震华

    2012-01-01

    Factor Xa is located at the intersection of the intrinsic and extrinsic pathways in the coagulation cascade. The newer anticoagulant drugs targeting factor Xa have the advantage of good efficacy, more convenience, no laboratory monitoring, and less bleeding side effect. Indirect factor Xa inhibitor fondaparinux, idraparinux, idrabiotaparinux, SR123781 and direct factor Xa inhibitor rivaroxaban, apixaban, betrixaban, edoxaban, eribaxaban, LY517717, YM150, letaxaban, otamixaban are the more studied drugs nowadays.%凝血因子Xa是内源性凝血系统和外源性凝血系统的交汇点.针对凝血因子Xa的新型抗凝药物具有疗效显著、使用方便、不需实验室监测、出血不良反应少等优点.间接凝血因子Xa抑制药璜达肝素、艾屈肝素、idrabiotaparinux、SR123781和直接凝血因子Xa抑制药利伐沙班、apixaban、betrixaban、edoxaban、eribaxaban、LY517717、YM150、letaxaban、奥米沙班是目前研究较多的药物.

  16. Comparison of coagulation factors and blood loss between O and non-O blood types following hydroxyethyl starch infusion

    OpenAIRE

    Choi, Soo Joo; Ahn, Hyun Joo; Lee, Jae Ik

    2010-01-01

    Background Individuals with type O blood are more likely to have reduced factor VIII and von Willebrand factor levels compared to their non-O counterparts. Hydroxyethyl starch (HES), which is widely used for blood volume replacement, can induce coagulopathy. Therefore, we tested whether blood type O patients show more coagulopathy and blood loss than non-O patients after infusion of 6% HES. Methods Thirty-four non-O and 20 type O patients scheduled for posterior lumbar interbody fusion (PLIF)...

  17. The M358R variant of α(1)-proteinase inhibitor inhibits coagulation factor VIIa.

    Science.gov (United States)

    Sheffield, William P; Bhakta, Varsha

    2016-02-12

    The naturally occurring M358R mutation of the plasma serpin α1-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(-1)sec(-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. PMID:26797521

  18. Ancylostoma caninum anticoagulant peptide: a hookworm-derived inhibitor of human coagulation factor Xa.

    OpenAIRE

    Cappello, M; Vlasuk, G P; Bergum, P W; Huang, S.; Hotez, P. J.

    1995-01-01

    Human hookworm infection is a major cause of gastrointestinal blood loss and iron deficiency anemia, affecting up to one billion people in the developing world. These soil-transmitted helminths cause blood loss during attachment to the intestinal mucosa by lacerating capillaries and ingesting extravasated blood. We have isolated the major anticoagulant used by adult worms to facilitate feeding and exacerbate intestinal blood loss. This 8.7-kDa peptide, named the Ancylostoma caninum anticoagul...

  19. A comparative study of tissue factor and kaolin on blood coagulation assays using rotational thromboelastometry and thromboelastography.

    Science.gov (United States)

    Peng, Henry T; Grodecki, Richard; Rizoli, Sandro; Shek, Pang N

    2016-01-01

    Rotational thromboelastometry (ROTEM) and thromboelastography (TEG) have been increasingly used to diagnose acute coagulopathy and guide blood transfusion. The tests are routinely performed using different triggering activators such as tissue factor and kaolin, which activate different pathways yielding different results. To optimize the global blood coagulation assays using ROTEM and TEG, we conducted a comparative study on the activation methods employing tissue factor and kaolin at different concentrations as well as standard reagents as recommended by the manufacturer of each device. Key parameter values were obtained at various assay conditions to evaluate and compare coagulation and fibrinolysis profiles of citrated whole blood collected from healthy volunteers. It was found that tissue factor reduced ROTEM clotting time and TEG R, and increased ROTEM clot formation time and TEG K in a concentration-dependent manner. In addition, tissue factor affected ROTEM alpha angle, and maximum clot firmness, especially in the absence of kaolin activation, whereas both ROTEM and TEG clot lysis (LI30, CL30, and LY30) remained unaffected. Moreover, kaolin reduced ROTEM clotting time and TEG R and K, but to a lesser extent than tissue factor, in-tem and ex-tem. Correlations in all corresponding parameters between ROTEM and TEG were observed, when the same activators were used in the assays compared with lesser correlations between standard kaolin TEG and ROTEM (INTEM/EXTEM). The two types of viscoelastic point-of-care devices provide different results, depending on the triggering reagent used to perform the assay. Optimal assay condition was obtained to reduce assay time and improve assay accuracy. PMID:26340454

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

    International Nuclear Information System (INIS)

    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)

  1. Limited promiscuity of HLA-DRB1 presented peptides derived of blood coagulation factor VIII.

    Directory of Open Access Journals (Sweden)

    Simon D van Haren

    Full Text Available The formation of inhibitory antibodies directed against coagulation factor VIII (FVIII is a severe complication in the treatment of hemophilia A patients. The induction of anti-FVIII antibodies is a CD4(+ T cell-dependent process. Activation of FVIII-specific CD4(+ T cells is dependent on the presentation of FVIII-derived peptides on MHC class II by antigen-presenting cells. Previously, we have shown that FVIII-pulsed human monocyte-derived dendritic cells can present peptides from several FVIII domains. In this study we show that FVIII peptides are presented on immature as well as mature dendritic cells. In immature dendritic cells half of the FVIII-loaded MHC class II molecules are retained within the cell, whereas in LPS-matured dendritic cells the majority of MHC class II/peptide complexes is present on the plasma membrane. Time-course studies revealed that presentation of FVIII-derived peptides was optimal between 12 and 24 hours after maturation but persisted for at least 96 hours. We also show that macrophages are able to internalize FVIII as efficiently as dendritic cells, however FVIII was presented on MHC class II with a lower efficiency and with different epitopes compared to dendritic cells. In total, 48 FVIII core-peptides were identified using a DCs derived of 8 different donors. Five HLA-promiscuous FVIII peptide regions were found - these were presented by at least 4 out of 8 donors. The remaining 42 peptide core regions in FVIII were presented by DCs derived from a single (30 peptides or two to three donors (12 peptides. Overall, our findings show that a broad repertoire of FVIII peptides can be presented on HLA-DR.

  2. Numerical Simulation of the Coagulation Dynamics of Blood

    OpenAIRE

    Bodnár, T.; Sequeira, A.

    2008-01-01

    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...

  3. Haemostatic effects of recombinant coagulation factor VIIa

    NARCIS (Netherlands)

    Lisman, Johannes Antonius

    2003-01-01

    Recombinant coagulation factor VIIa (rFVIIa) has recently become available for treatment of patients with inhibitor-complicated haemophilia. It has been postulated that rFVIIa could become a universal haemostatic agent. Case reports and small studies confirm efficacy and safety of rFVIIa in a variet

  4. 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

  5. Influence of Blood Lipids on Global Coagulation Test Results

    OpenAIRE

    Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon; Kim, Hyun Kyung

    2014-01-01

    Background High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). Methods PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absen...

  6. Perioperative blood transfusion of coagulation factor deficiency in children%凝血因子缺乏患儿的围手术期输血

    Institute of Scientific and Technical Information of China (English)

    马廉; 王鸿武; 蒋学武

    2014-01-01

    Perioperative blood transfusion therapy for coagulation factor deficiency in children is very important to save patient's life or conducive to the postoperative recovery.With the advances in transfusion medicine,the cooperation through pediatric hematologists and surgeons in the perioperative period,more and more operation of children accompany coagulation factor deficiency can be safety finished.Different types of coagulation factor deficiency in children are treated by high-purity clotting factor,in order to correct abnormal coagulation factors levels.Clinical data showed that coagulation factor deficiency in children after proper treatment can be safely performed surgical procedure.%凝血因子缺乏症患儿的围手术期输血治疗十分重要,能挽救患儿的生命或有利于患儿术后恢复.随着输血医学的不断进步,在围手术期针对不同类型凝血因子缺乏的患儿通过补充高纯度的凝血因子等替代疗法,纠正凝血因子异常,保障各类手术的安全进行.临床数据显示凝血因子缺乏症患儿经过适当的处理、治疗,可安全地进行手术操作.

  7. PHYSIOLOGY OF BLOOD COAGULATION (II)

    OpenAIRE

    B. Ţuţuianu

    2007-01-01

    Coagulation cascade was untill recently the only model used to explain the physiological and pathological reactions during clot formation. Dr. Maureane Hoffman and her team suggested a cell-based model for coagulation, which takes place (according to this model) in three phases: initiation, amplification and propagation. This theory does not deny the coagulation cascade. It only says that the leading role in the whole process is held by the cells and that the „intrinsic” and the „extinsic” pa...

  8. 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

  9. A high fat meal activates blood coagulation factor VII in rats

    DEFF Research Database (Denmark)

    Olsen, Aage K; Bladbjerg, Else M; Hansen, Axel K;

    2002-01-01

    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....../L), and FVIIa was significantly raised at 4 h (54 U/L) and 6 h (58 U/L) compared with baseline (29 U/L). No postprandial changes in FVIIc, FVIIam and TAT were observed. Glucose administration did not affect any variable. We conclude that the LEW/Mol rat is a promising model for use in future studies of...

  10. PHYSIOLOGY OF BLOOD COAGULATION (II

    Directory of Open Access Journals (Sweden)

    B. Ţuţuianu

    2007-07-01

    Full Text Available Coagulation cascade was untill recently the only model used to explain the physiological and pathological reactions during clot formation. Dr. Maureane Hoffman and her team suggested a cell-based model for coagulation, which takes place (according to this model in three phases: initiation, amplification and propagation. This theory does not deny the coagulation cascade. It only says that the leading role in the whole process is held by the cells and that the „intrinsic” and the „extinsic” pathways operate in parallel on different cell surfaces. Using this model, a better understanding of the reactions in vivo during coagulation is achieved, together with answers related to clinical-based questions like „why haemophiliacs bleed?”.

  11. Coagulation-Inflammatory Network: Anti-inflammatory Effect of Natural Coagulation Inhibitors

    Institute of Scientific and Technical Information of China (English)

    贺石林

    2001-01-01

    @@ Considerable evidence has accumulated to indicated that the serine protease in blood clotting process not only participate in the activation of coagulation factors,but also result in a series of cell responses particularly involved in inflammation process through appropriate receptors.

  12. Activation of blood coagulation in autoimmune skin disorders.

    Science.gov (United States)

    Cugno, Massimo; Tedeschi, Alberto; Crosti, Carlo; Marzano, Angelo V

    2009-09-01

    The immune system and blood coagulation are simultaneously activated in several inflammatory systemic disorders, such as lupus erythematosus, rheumatoid arthritis and inflammatory bowel diseases. Proinflammatory cytokines, such as IL-6 and TNF-alpha, induce the expression of tissue factor, the main initiator of blood coagulation. Activated proteases of coagulation in turn act on protease-activated receptors, inducing the expression of various proinflammatory cytokines. This cross-talk between inflammation and coagulation amplifies and maintains the activation of both systems. This review focuses on three skin disorders: chronic urticaria (CU), which is considered autoimmune in approximately 50% of cases, bullous pemphigoid (BP), which is the prototype of autoimmune blistering disease, and psoriasis, which is an immune-mediated dermatitis. In CU, the activation of coagulation, which is due to the involvement of eosinophils and tissue factor pathways with the generation of thrombin, has local implications by increasing dermal vascular permeability. Preliminary data indicate that anticoagulant treatment with heparin and warfarin may be effective in reducing the symptoms of this disorder. In BP, the activation of coagulation seems to have both local and systemic implications. Locally, eosinophils and thrombin participate in bulla formation and tissue damage; systemically, the activation of coagulation may explain the increased thrombotic risk observed in these patients. In psoriasis, the activation of coagulation seems to be mainly systemic, potentially contributing to the increased cardiovascular risk associated with this disease. PMID:20477646

  13. Thymoquinone Modulates Blood Coagulation in Vitro via Its Effects on Inflammatory and Coagulation Pathways

    OpenAIRE

    Vandhana Muralidharan-Chari; Jaehan Kim; Ahlam Abuawad; Mubeena Naeem; Huadong Cui; Mousa, Shaker A

    2016-01-01

    Thymoquinone (THQ) is a major component of black seeds. Given that both THQ and black seeds exhibit anti-cancer and anti-inflammatory activities, we hypothesized that THQ will affect cancer-associated thrombosis (CAT), which is primarily triggered by tissue factor (TF) and inflammation. The effect of both black seed-extracted and purchased (“pure”) THQ on normal blood coagulation was tested with in vitro thromboelastography (TEG) and activated partial thromboplastin time (aPTT) coagulation as...

  14. Impaired Activity of Blood Coagulant Factor XIII in Patients with Necrotizing Enterocolitis.

    Science.gov (United States)

    Tao, Guo-Zhong; Liu, Bo; Zhang, Rong; Liu, Gigi; Abdullah, Fizan; Harris, Mary Cay; Brandt, Mary L; Ehrenkranz, Richard A; Bowers, Corinna; Martin, Camilia R; Moss, R Lawrence; Sylvester, Karl G

    2015-08-17

    Necrotizing enterocolitis (NEC) is the most common gastrointestinal (GI) medical/surgical emergency of the newborn and a leading cause of preterm neonate morbidity and mortality. NEC is a challenge to diagnose since it often shares similar clinical features with neonatal sepsis. In the present study, plasma protein profiling was compared among NEC, sepsis and control cohorts using gel electrophoresis, immunoblot and mass spectrometry. We observed significant impairment in the formation of fibrinogen-γ dimers (FGG-dimer) in the plasma of newborns with NEC that could efficiently differentiate NEC and sepsis with a high level of sensitivity and specificity. Interestingly, the impaired FGG-dimer formation could be restored in NEC plasma by the addition of exogenous active factor XIII (FXIII). Enzymatic activity of FXIII was determined to be significantly lower in NEC subject plasma for crosslinking FGG when compared to sepsis. These findings demonstrate a potential novel biomarker and related biologic mechanism for diagnosing NEC, as well as suggest a possible therapeutic strategy.

  15. Characterization of the gene for the a subunit of human factor XIII (plasma transglutaminase), a blood coagulation factor

    Energy Technology Data Exchange (ETDEWEB)

    Ichinose, A.; Davie, E.W. (Univ. of Washington, Seattle (USA))

    1988-08-01

    Factor XIII (plasma transglutaminase, fibrin stabilizing factor) is a glycoprotein that circulates in blood as a tetramer (a{sub 2}b{sub 2}) consisting of two a and two b subunits. The primary structures of the a and b subunits of human factor XIII have been reported by a combination of cDNA cloning and amino acid sequence analysis. To establish the gene structure of the a subunit for factor XIII, several human genomic libraries were screened by using the cDNA encoding the a subunit as a probe. Among {approx}5 {times} 10{sup 7} recombinant phage, 121 have been shown to contain an insert encoding a portion of the a subunit. Twenty-five unique clones were than characterized by restriction mapping, Southern blotting, and DNA sequencing. Overlapping clones encoding the a subunit of factor XIII span >160 kilobases. DNA sequence analysis revealed that the activation peptide released by thrombin, the active site cysteine region, the two putative calcium-binding regions, and the thrombin cleavage site leading to inactivation are encoded by separate exons. This suggest that the introns may separate the a subunit into functional and structural domains. A comparison of the amino acid sequence deduced from the genomic DNA sequence with those deduced from cDNA or determined by amino acid sequence analysis of the plasma and placental proteins revealed apparent amino acid polymorphisms in six positions of the polypeptide chain of the a subunit.

  16. Coagulation Factor IX for Hemophilia B Therapy


    OpenAIRE

    Orlova, N.; Kovnir, S.; Vorobiev, I.; Gabibov, A.

    2012-01-01

    Factor IX is a zymogen enzyme of the blood coagulation cascade. Inherited absence or deficit of the IX functional factor causes bleeding disorder hemophilia B, which requires constant protein replacement therapy. Reviewed herein are the current state in the manufacturing of FIX, improved variants of the recombinant protein for therapy, transgenic organisms for obtaining FIX, and the advances in the gene therapy of hemophilia B.

  17. 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

  18. 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...

  19. Spatial localization of bacteria controls coagulation of human blood by ‘quorum acting'

    OpenAIRE

    Kastrup, Christian J; Boedicker, James Q.; Pomerantsev, Andrei P.; Moayeri, Mahtab; Bian, Yao; Pompano, Rebecca R; Kline, Timothy R.; Sylvestre, Patricia; Shen, Feng; Leppla, Stephen H.; Tang, Wei-Jen; Ismagilov, Rustem F.

    2008-01-01

    Blood coagulation often accompanies bacterial infections and sepsis and is generally accepted as a consequence of immune responses. Though many bacterial species can directly activate individual coagulation factors, they have not been shown to directly initiate the coagulation cascade that precedes clot formation. Here we demonstrated, using microfluidics and surface patterning, that the spatial localization of bacteria substantially affects coagulation of human and mouse blood and plasma. Ba...

  20. Crystallization and preliminary X-ray crystallographic analysis of blood coagulation factor V-activating proteinase (RVV-V) from Russell’s viper venom

    International Nuclear Information System (INIS)

    The crystallization and preliminary X-ray crystallographic analysis of blood coagulation factor V-activating proteinase are reported. The best crystal diffracted to 1.9 Å resolution. Russell’s viper venom blood coagulation factor V activator (RVV-V) is a thrombin-like serine proteinase that specifically activates factor V by cleaving a single peptide bond between Arg1545 and Ser1546. Activated factor V combines with activated factor X produced by the enzyme RVV-X in the venom to form the prothombinase complex, which can induce disseminated intravascular coagulopathy in envenomated animals. In the current study, RVV-V was crystallized in order to attempt to understand its substrate specificity for factor V. Four distinct crystal forms of RVV-V were obtained using the sitting-drop vapour-diffusion method and diffraction data sets were collected on SPring-8 beamlines. The best crystal of RVV-V generated data sets to 1.9 Å resolution

  1. Principles of dielectric blood coagulometry as a comprehensive coagulation test.

    Science.gov (United States)

    Hayashi, Yoshihito; Brun, Marc-Aurèle; Machida, Kenzo; Nagasawa, Masayuki

    2015-10-01

    Dielectric blood coagulometry (DBCM) is intended to support hemostasis management by providing comprehensive information on blood coagulation from automated, time-dependent measurements of whole blood dielectric spectra. We discuss the relationship between the series of blood coagulation reactions, especially the aggregation and deformation of erythrocytes, and the dielectric response with the help of clot structure electron microscope observations. Dielectric response to the spontaneous coagulation after recalcification presented three distinct phases that correspond to (P1) rouleau formation before the onset of clotting, (P2) erythrocyte aggregation and reconstitution of aggregates accompanying early fibrin formation, and (P3) erythrocyte shape transformation and/or structure changes within aggregates after the stable fibrin network is formed and platelet contraction occurs. Disappearance of the second phase was observed upon addition of tissue factor and ellagic acid for activation of extrinsic and intrinsic pathways, respectively, which is attributable to accelerated thrombin generation. A series of control experiments revealed that the amplitude and/or quickness of dielectric response reflect platelet function, fibrin polymerization, fibrinolysis activity, and heparin activity. Therefore, DBCM sensitively measures blood coagulation via erythrocytes aggregation and shape changes and their impact on the dielectric permittivity, making possible the development of the battery of assays needed for comprehensive coagulation testing. PMID:26368847

  2. 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

    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...

  3. Skeletal muscle-specific expression of human blood coagulation factor Ⅸ rescues factor Ⅸ deficiency mouse by AAV-mediated gene transfer

    Institute of Scientific and Technical Information of China (English)

    赖立辉; 陈立; 卢大儒; 王琪; 高啸波; 邱信芳; Jerry; L.Hsueh; 薛京伦; 王健民; 周虹

    1999-01-01

    The efficacy of recombinant adeno-associated virus (AAV) vector to deliver and express human blood clotting factor DC (hFIX) gene in skeletal muscle of coagulation factor IX deficiency mouse strain (FactorIX-knockout) is e-valuated. The muscle creatine kinase enhancer (MCK) and βactin promoter ((3A) were used to drive the hFIX minigene (hFIXml), which was flanked by AAV inverted terminal repeats (ITRs). Following intramuscular injection of high liter (2.5 x 1011 vector genomes/mL) of AAV, increased hFIX expression (256 ng/mL of plasma) was achieved. The time course of hFIX expression demonstrated that the expression level gradually increased over a period of two weeks before anti-hFIX antibodies developed in mouse circulating plasma. Those results provided a promising evidence that rAAV-me-diated gene transfer and skeletal muscle-specific expression of hFIX is a feasible strategy for treating patients for hemophilia B.

  4. Evaluation of coagulation factors in fresh frozen plasma treated with riboflavin and ultraviolet light

    Directory of Open Access Journals (Sweden)

    Antić Ana

    2012-01-01

    Full Text Available Background/Aim. Pathogen inactivation in blood products using riboflavin and ultraviolet (UV light represents a proactive approach to blood safety, not only for known infectious agents but also for new ones or not yet recognized as threats to the blood supply. This method inactivates a virus, bacteria, fungus, or protozoan pathogen from the blood product without damaging its function or shelf-life. The aim of the study was to study the influence of photoinactivation using riboflavin on the concentration of coagulation factors and coagulation inhibitors in plasma that was treated before freezing. Methods. The examination included 30 units of plasma, separated from whole blood donated by voluntary blood donors around 6 h from the moment of collection. They were treated by riboflavin (35 mL and UV rays (6.24 J/mL, 265-370 nm on Mirasol aparature (Caridian BCT Biotechnologies, USA in approximate duration of 6 min. The samples for examining were taken before (K - control units and after illumination (I - illuminated units. Results. Comparing the middle values of coagulation factors in the control and illuminated units we noticed their statistically significant decrease in illuminated units (p < 0.001, but the activity of coagulation ones was still in the reference range. The most sensitive coagulation factors to photoinactivation were FVIII, FIX and FXI (21.99%, 20.54% and 17.26% loss, respectively. Anticoagulant factors were better preseved than coagulation factors. Conclusion. Plasma separated from whole blood donation within 6 h, treated with riboflavin and UV light within 6 h from separation and frozen at temperature below -30ºC within 24 h, shows good retention of pro- and anticoagulation activity.

  5. Thymoquinone Modulates Blood Coagulation in Vitro via Its Effects on Inflammatory and Coagulation Pathways.

    Science.gov (United States)

    Muralidharan-Chari, Vandhana; Kim, Jaehan; Abuawad, Ahlam; Naeem, Mubeena; Cui, Huadong; Mousa, Shaker A

    2016-01-01

    Thymoquinone (THQ) is a major component of black seeds. Given that both THQ and black seeds exhibit anti-cancer and anti-inflammatory activities, we hypothesized that THQ will affect cancer-associated thrombosis (CAT), which is primarily triggered by tissue factor (TF) and inflammation. The effect of both black seed-extracted and purchased ("pure") THQ on normal blood coagulation was tested with in vitro thromboelastography (TEG) and activated partial thromboplastin time (aPTT) coagulation assays. The effect of pure THQ on CAT was tested with aPTT assay using pancreatic cancer cell lines that are either positive or negative for TF, and with TEG assay using lipopolysaccharide as an inflammatory trigger. Additionally, the direct effect of THQ on the inactivation of factors IIa and Xa was assessed. Since TNF-α facilitates crosstalk between inflammation and thrombosis by triggering the NF-κB pathway, we tested THQ's ability to interfere with this communication with a luciferase assay. Both extracted and pure THQ had minimal effects on normal blood coagulation. Pure THQ reversed CAT initiated by both TF and inflammation to basal levels (p coagulation and can reverse CAT in vitro, possibly by interfering with the crosstalk between inflammation and coagulation. This study suggests the utility of THQ as a preventative anticoagulant and/or as a supplement to existing chemotherapies and anticoagulant therapies. PMID:27043539

  6. 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.

  7. 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.

  8. Thymoquinone Modulates Blood Coagulation in Vitro via Its Effects on Inflammatory and Coagulation Pathways

    Directory of Open Access Journals (Sweden)

    Vandhana Muralidharan-Chari

    2016-03-01

    Full Text Available Thymoquinone (THQ is a major component of black seeds. Given that both THQ and black seeds exhibit anti-cancer and anti-inflammatory activities, we hypothesized that THQ will affect cancer-associated thrombosis (CAT, which is primarily triggered by tissue factor (TF and inflammation. The effect of both black seed-extracted and purchased (“pure” THQ on normal blood coagulation was tested with in vitro thromboelastography (TEG and activated partial thromboplastin time (aPTT coagulation assays. The effect of pure THQ on CAT was tested with aPTT assay using pancreatic cancer cell lines that are either positive or negative for TF, and with TEG assay using lipopolysaccharide as an inflammatory trigger. Additionally, the direct effect of THQ on the inactivation of factors IIa and Xa was assessed. Since TNF-α facilitates crosstalk between inflammation and thrombosis by triggering the NF-κB pathway, we tested THQ’s ability to interfere with this communication with a luciferase assay. Both extracted and pure THQ had minimal effects on normal blood coagulation. Pure THQ reversed CAT initiated by both TF and inflammation to basal levels (p < 0.001. Mechanistically, while THQ had minimal to no effect on factor IIa and Xa inactivation, it strongly reduced the effects of TNF-α on NF-κB elements (p < 0.001. THQ has a minimal effect on basal coagulation and can reverse CAT in vitro, possibly by interfering with the crosstalk between inflammation and coagulation. This study suggests the utility of THQ as a preventative anticoagulant and/or as a supplement to existing chemotherapies and anticoagulant therapies.

  9. Functional regions in coagulation factor VIII explored by mass spectrometry

    NARCIS (Netherlands)

    Bloem, E.

    2013-01-01

    The molecular mechanisms behind the function of factor VIII (FVIII) have remained poorly understood. FVIII acts in the blood coagulation cascade as cofactor for activated factor IX (FIXa) in the membrane bound activated factor X generating (FXase) complex. A functional absence in FVIII leads to the

  10. 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...... (1929 nmol/l*min vs. 1872 nmol/l*min, P = 0.02). Addition of the FXIIa inhibitor Corn Trypsin Inhibitor (CTI) prior to the thrombin generation test eliminated the ETP difference suggesting that hand heating activates the FXII-dependent coagulation pathway.......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...

  11. A loop of coagulation factor VIIa influencing macromolecular substrate specificity

    DEFF Research Database (Denmark)

    Bjelke, Jais R; Persson, Egon; Rasmussen, Hanne B;

    2006-01-01

    . The resulting variant exhibited increased intrinsic activity, concurrent with maturation of the active site, a less accessible N-terminus, and, interestingly, an altered macromolecular substrate specificity reflected in an increased ability to cleave factor IX (FIX) and a decreased rate of FX activation....../Met(298{156})Lys-FVIIa with almost the same activity and specificity profile. We conclude that a lysine residue in position 298{156} of FVIIa requires a hydrophilic environment to be fully accommodated. This position appears critical for substrate specificity among the proteases of the blood coagulation......Coagulation factor VIIa (FVIIa) belongs to a family of proteases being part of the stepwise, self-amplifying blood coagulation cascade. To investigate the impact of the mutation Met(298{156})Lys in FVIIa, we replaced the Gly(283{140})-Met(298{156}) loop with the corresponding loop of factor Xa...

  12. 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.

  13. Influence of blood flow on the coagulation cascade

    DEFF Research Database (Denmark)

    The influence of diffusion and convetive flows on the blood coagulation cascade is investigated for a controlled perfusion experiment. We present a cartoon model and reaction schemes for parts of the coagulation cascade with sunsequent set up of a mathematical model in two space dimensions plus one...

  14. Fibrinolysis and the control of blood coagulation

    OpenAIRE

    Chapin, John C.; Hajjar, Katherine A.

    2014-01-01

    Fibrin plays an essential role in hemostasis as both the primary product of the coagulation cascade and the ultimate substrate for fibrinolysis. Fibrinolysis efficiency is greatly influenced by clot structure, fibrinogen isoforms and polymorphisms, the rate of thrombin generation, the reactivity of thrombus-associated cells such as platelets, and the overall biochemical environment. Regulation of the fibrinolytic system, like that of the coagulation cascade, is accomplished by a wide array of...

  15. A novel mutation in a patient with congenital coagulation factor Ⅻ deficiency

    Institute of Scientific and Technical Information of China (English)

    FENG Ying; YE Xu; PANG Ying; DAI Jing; WANG Xue-feng; ZHOU Xu-hong

    2008-01-01

    @@ Human coagulation factor Ⅻ(FⅫ),also called Hageman factor,is a plasma plycoprotein that is functionally deficient in individuals with Hageman trait:which is an inhefited trait discovered by chance during preoperative blood coagulation screening tests.FⅫ is a single-chain 596-amino-acid zymogen of a serine protease with an approximate molecular weight of 80 000.

  16. Blood hibernation: a novel strategy to inhibit systemic inflammation and coagulation induced by cardiopulmonary bypass

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jing; WU Xiao-dong; LIN Ke; Raphael C. Lui; AN Qi; TAO Kai-yu; DU Lei; LIU Jin

    2010-01-01

    Background Inflammation and coagulation are two intimately cross-linked defense mechanisms of most, if not all organisms to injuries. During cardiopulmonary bypass (CPB), these two process-is are activated and interact with each other through several common pathways, which may result in subsequent organ dysfunction. In the present study, we hypothesized that the addition of nitric oxide, prostaglandin E1 (PGE1), and aprotinin to the systemic circulation, hereby referred to as blood hibernation, would attenuate the inflammation and coagulation induced by CPB. Methods Thirty adult mongrel dogs were equally divided into five groups, anesthetized and placed on hypothermic CPB (32 C). Each group received respectively the following treatments: (1) inhalation of 40 ppm nitric oxide; (2) intravenous infusion of 20 ng·kg-1·min-1 of PGE1; (3) 80 000 kallikrein inhibitor units (KIU)/kg of aprotinin; (4) the combination of all three agents (blood hibernation group); and (5) no treatment (control group) during CPB. Activation of leukocyte, platelet, endothelial cell, and formation of thrombin were assessed after CPB.Results As compared with the other four groups, leukocyte counts were higher, while plasma elastase, interleukin-8, CD11b mRNA expression, myeloperoxidase activities and lung tissue leukocyte counts were lower in the blood hibernation group (P<0.05 versus other four groups after CPB). Plasma prothrombin fragment (PTF)1+2, and platelet activation factors were lower, while platelet counts were higher in the blood hibernation group (P<0.05 versus other four groups at 6 and 12 hours after CPB). Electron microscopy showed endothelial pseudopods protrusion, with cell adherence in all four groups except the blood hibernation group where endothelial cells remained intact.Conclusion Blood hibernation, effected by the addition of nitric oxide, PGE1 and aprotinin to the circulating blood during extra-corporeal circulation, was observed to attenuate the inflammation and

  17. Influence of Blood Collection Systems on Coagulation Tests

    Directory of Open Access Journals (Sweden)

    Soner Yavaş

    2012-12-01

    Full Text Available OBJECTIVE: Coagulation tests are influenced by pre-analytic conditions such as blood collection systems. Change of glass collection tubes with plastic ones will cause alteration of the test results. The aim of this study was to compare three plastic blood collection tubes with a standard glass blood collection tube and each plastic collection tube with the other two for possible additional tube-to- tube differences. METHODS: A total of 284 blood samples were obtained from 42 patients receiving warfarin during their routine controls, besides 29 healthy volunteers. Subgroup analyses were done according to health status. RESULTS: Our study demonstrated that different blood collection tubes have a statistically significant influence on coagulation tests. The magnitude of the effect depends on the tube used. However most of the tests performed on samples obtained from any tube correlated significantly with results obtained from other tube samples. CONCLUSION: Although blood collection tubes with different brands or properties will have distinct effects on coagulation tests, the influence of these blood collection tubes may be relatively small to interfere with decision-making on dose prescription, therefore lack clinical importance. Correlations between the results showed that, one of these plastic blood collection tubes tested in our study, can be used interchangably for a wide variety of coagulation assays.

  18. Coagulation factor Xa drives tumor cells into apoptosis through BH3-only protein Bim up-regulation

    NARCIS (Netherlands)

    Borensztajn, Keren S.; Bijlsma, Maarten F.; Groot, Angelique P.; Bruggemann, Lois W.; Versteeg, Henri H.; Reitsma, Pieter H.; Peppelenbosch, Maikel P.; Spek, C. Arnold

    2007-01-01

    Coagulation Factor (F)Xa is a serine protease that plays a crucial role during blood coagulation by converting prothrombin into active thrombin. Recently, however, it emerged that besides this role in coagulation, FXa induces intracellular signaling leading to different cellular effects. Here, we sh

  19. Changing characteristic of blood coagulation factors and their correlation with blood coagulation status in different hepatic diseases%不同类型肝病患者凝血因子变化规律及其与凝血状态的关系

    Institute of Scientific and Technical Information of China (English)

    陈静; 段钟平; 白丽; 赵军; 丁美; 童新元; 丛玉隆

    2012-01-01

    202.9;肝衰竭组:344.7±214.6;均高于正常对照组的12.9±8.1;F=8.619,P<0.05);FⅧ∶C检测值(慢性乙型肝炎组:157.2±53.4;肝硬化组:206.9±86.9;肝衰竭组:335.7±117.7;均高于正常对照组的105.5±46.2;F=13.418,P<0.05).结论 肝脏疾病随着病情发展,由肝实质细胞合成的促抗凝成分伴发平行减少、纤溶活性增强、肝外合成凝血相关蛋白TFPI、TM、vWF及TF释放入血增多.终末期肝病患者凝血与抗凝平衡失调,可能与以上原因有关.TFPI、TM、vWF及TF在肝病轻度阶段即发生明显变化,可作为早期监测血管内皮细胞损伤敏感指标.%Objective To investigate the correlation between procoagulation factors and anticoagulation factors synthesized by the liver,and the correlation between fibrin degradation products (FDP) and D-dimer (D-D) concentration and coagulation proteins synthesized by extra-hepatic tissues,in different liver diseases; to explore the relationship between coagulation and bleeding in hepatic diseases.Methods Chronic hepatitis B (CHB) patients,CHB-related liver cirrhosis patients,CHB-related liver failure patients and healthy (normal) controls were selected for study and provided blood samples for analysis.The activity of coagulation factors (F) Ⅱ,Ⅴ,Ⅶ ,Ⅷ , Ⅸ,Ⅹ,Ⅺ,and Ⅻ was detected using the one-stage clotting method.Coagulogram analysis,including activated partial thromboplastia time (APTT),thrombin time (TT),and prothrombin time (PT),was conducted by the solidification method.Antithrombin Ⅲ (AT-Ⅲ ) and protein C (PC) activities were measured by chromogenic substrate assay.FDP concentration was detected using immunoturbidimetry.Tissue factor pathway inhibitor (TFPI),thrombomodulin (TM),von Willebrand factor (vWF),and tissue factor (TF) concentrations were measured by enzyme-linked immunosorbent assay (ELISA).Results With the exception of FⅧ ,coagulation factors and anticoagulant proteins synthesized by the liver were decreased

  20. 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

  1. C-reactive protein prolongs blood coagulation time in phospholipids-dependent coagulation tests

    Directory of Open Access Journals (Sweden)

    L D Kozmin

    2003-01-01

    Full Text Available C-refctive protein prolongs blood coagulation time in phospholipids-dependent coagulation tests. O.P. Bliznukov, L.D. Kostin, A.J. Martinov, T.A. Lisitsina, T.M. Reshetnyak, V.J. Lauga Objective. To study influence of different CRP forms on blood clotting time in standard phospholipid clotting tests. Material and methods. Purified native CRP. monomeric CRP (0-1.6 M, immune complexes of native CRP and rabbit polyclonal anti-CRP antibodies (1.6 M were added to blood plasma of healthy donors. Blood clotting time was registered using optical coagulometer. Phospholipid dependent prothrombin time (PT, activated partial tromboplastin time (APTT, kaolin clotting time (KCT with kaolin and ellagic acid, dilute Russel viper venom time (dRVVT were determined. Results. Native CRP was able to increase blood clotting time in all mentioned clotting tests, excluding prothrombin time. CRP influence on blood clotting time showed a concentration dependence. Polyclonal rabbit anti-CRP antibodies had no inhibitory effect on CRP prolonged blood clotting time. Monomeric CRP (0-1.6 M had no influence on blood clotting time in all phospholipid-dependent clotting tests.

  2. Multifrequency acoustics as a probe of mesoscopic blood coagulation dynamics

    Science.gov (United States)

    Ganesan, Adarsh; Rajendran, Gokulnath; Ercole, Ari; Seshia, Ashwin

    2016-08-01

    Coagulation is a complex enzymatic polymerisation cascade. Disordered coagulation is common in medicine and may be life-threatening yet clinical assays are typically bulky and/or provide an incomplete picture of clot mechanical evolution. We present the adaptation of an in-plane acoustic wave device: quartz crystal microbalance with dissipation at multiple harmonics to determine the time-evolution of mesoscale mechanical properties of clot formation in vitro. This approach is sensitive to changes in surface and bulk clot structure in various models of induced coagulopathy. Furthermore, we are able to show that clot formation at surfaces has different kinetics and mechanical strength to that in the bulk, which may have implications for the design of bioprosthetic materials. The "Multifrequency acoustics" approach thus enables unique capability to portray biological processes concerning blood coagulation.

  3. 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.

  4. The first EGF domain of coagulation factor IX attenuates cell adhesion and induces apoptosis.

    Science.gov (United States)

    Ishikawa, Tomomi; Kitano, Hisataka; Mamiya, Atsushi; Kokubun, Shinichiro; Hidai, Chiaki

    2016-07-01

    Coagulation factor IX (FIX) is an essential plasma protein for blood coagulation. The first epidermal growth factor (EGF) motif of FIX (EGF-F9) has been reported to attenuate cell adhesion to the extracellular matrix (ECM). The purpose of the present study was to determine the effects of this motif on cell adhesion and apoptosis. Treatment with a recombinant EGF-F9 attenuated cell adhesion to the ECM within 10 min. De-adhesion assays with native FIX recombinant FIX deletion mutant proteins suggested that the de-adhesion activity of EGF-F9 requires the same process of FIX activation as that which occurs for coagulation activity. The recombinant EGF-F9 increased lactate dehydrogenase (LDH) activity release into the medium and increased the number of cells stained with annexin V and activated caspase-3, by 8.8- and 2.7-fold respectively, indicating that EGF-F9 induced apoptosis. Activated caspase-3 increased very rapidly after only 5 min of administration of recombinant EGF-F9. Treatment with EGF-F9 increased the level of phosphorylated p38 mitogen-activated protein kinase (MAPK), but not that of phosphorylated MAPK 44/42 or c-Jun N-terminal kinase (JNK). Inhibitors of caspase-3 suppressed the release of LDH. Caspase-3 inhibitors also suppressed the attenuation of cell adhesion and phosphorylation of p38 MAPK by EGF-F9. Our data indicated that EGF-F9 activated signals for apoptosis and induced de-adhesion in a caspase-3 dependent manner. PMID:27129300

  5. Effects of tissue factor and tissue factor pathway inhibitor on sepsis-induced abnormal coagulation%组织因子、组织因子途径抑制物对脓毒症凝血异常的影响

    Institute of Scientific and Technical Information of China (English)

    郑少玲; 郭振辉; 孙杰; 姜巧; 陈蕊

    2012-01-01

    Objective To investigate the effects of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) expression and balance on abnormal coagulation in sepsis. Methods 72 KM mice were performed cecal ligation and puncture (CLP), and divided into the normal group, sham-operated group and model group. According to the different time points (2, 4, 8, 12 h), the three group were divided into 4 subgroups respectively, each group had 6 mice. The level of platelet and coagulation markers were observed, and the blood concentration of TF and TFPI was detected by enzyme-linked immunosorbent assay (ELISA). Results Compared with normal group and sham-operated group, the concentration of PT, TT, APTT and DD increased significantly, while Fbg and PLT decreased in the model group at 12 h after CLP (P < 0.05). The concentration of TF and TFPI increased significantly in the model group at 2 h after CLP, each group had significant differences (P < 0.05). With time extension, the concentration of TF continually increased, but the concentration of TFPI showed inversely. Conclusion In sepsis, thrombocytopenia and imbalance of TF and TFPI expression may be key factors induced abnormal coagulation and MODS.%目的 探讨脓毒症时组织因子(tissue factor,TF)与组织因子途径抑制剂(tissue factor pathway inhibitor,TFPI)的表达及其平衡对凝血异常的影响.方法 昆明小鼠72只采用盲肠结扎穿孔模型(cecal ligation and puncture,CLP),分为正常组、假手术组和造模组,每组根据不同时间点(2、4、8、12 h)分4个亚组,每个亚组各6只,检测血小板计数和凝血指标,采用ELISA法检测血浆TF和TFPI浓度.结果 盲肠结扎穿孔后,造模12 h组PT、TT、APTT和DD显著升高,Fbg和PLT计数显著降低,与正常组及假手术组比较,差异有统计学意义(P < 0.05).造模2 h组TF与TFPI均显著升高,各组间比较差异有统计学意义(P < 0.05);且TF浓度随时间呈进行性升高,而TFPI未见进一步升高.结论 脓

  6. [Roles of coagulation pathway and factor Xa in chronic kidney disease (CKD)].

    Science.gov (United States)

    Ono, Takahiko

    2012-01-01

    Considering that fibrin deposition is observed in glomerulonephritis as well as in diabetic nephropathy, we performed studies to clarify the roles of the coagulation pathway and the active type of coagulation factor X (factor Xa) in the development of chronic kidney disease (CKD) using animal models. Factor Xa activates various cell types through protease-activated receptor 2 (PAR2). Several in vitro studies have demonstrated that PAR2 can mediate factor Xa signaling, but not thrombin signaling. Coagulation processes proceed together with the extracellular matrix (ECM) accumulation through factor V expression in rat Thy-1 nephritis. DX-9065a, a factor Xa inhibitor, suppresses this type of glomerulonephritis. The factor Xa inhibitor danaparoid ameliorated proteinuria, cellular proliferation, and fibrin deposition in lipopolysaccharide (LPS)-triggered activation of High IgA (HIGA) strain of ddY mice. Another factor Xa inhibitor, fondaparinux, suppressed urinary protein, glomerular hypertrophy, and connective tissue growth factor (CTGF), and ECM protein deposition together with angiogenesis in diabetic db/db mice. Finally, in the model of peritoneal fibrosis, fondaparinux treatment decreased the thickness of submesothelial fibrotic tissue and angiogenesis. In consideration of the results to potential human therapy, factor Xa regulation may be promising for the treatment of the aggravation in glomerulonephritis and of the early phase of diabetic nephropathy. In the near future, novel factor Xa inhibitors with the characteristics of oral administration and biliary elimination may appear in the clinical use for treatment of cardiovascular diseases. PMID:22465921

  7. Combined deficiency of coagulation factors V and VIII: an update.

    Science.gov (United States)

    Zheng, Chunlei; Zhang, Bin

    2013-09-01

    Combined deficiency of factor V (FV) and FVIII (F5F8D) is an autosomal recessive bleeding disorder characterized by simultaneous decreases of both coagulation factors. This review summarizes recent reports on the clinical presentations, treatments, and molecular mechanism of F5F8D. Genetic studies identified LMAN1 and MCFD2 as causative genes for this disorder, revealing a previously unknown intracellular transport pathway shared by the two important blood coagulation factors. LMAN1 and MCFD2 form a Ca2+-dependent cargo receptor complex that functions in the transport of FV/FVIII from the endoplasmic reticulum (ER) to the Golgi. Disrupting the LMAN1-MCFD2 receptor, complex formation is the primary molecular defect of missense mutations leading to F5F8D. The EF-hand domains of MCFD2 are necessary and sufficient for the interactions with both LMAN1 and FV/FVIII. Similarly, the carbohydrate recognition domain of LMAN1 contains distinct and separable binding sites for both MCFD2 and FV/FVIII. Therefore, FV and FVIII likely carry duel sorting signals that are separately recognized by LMAN1 and MCFD2 and necessary for the efficient ER-to-Golgi transport. FV and FVIII likely bind LMAN1 through the high-mannose N-linked glycans under the higher Ca2+ conditions in the ER and dissociate in the lower Ca2+ environment of the ER-Golgi intermediate compartment. PMID:23852824

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

    Directory of Open Access Journals (Sweden)

    M. A. Gavrilenko

    2014-02-01

    Full Text Available Background. Actuality of the problem is determined by the high prevalence of periodontal tissues inflammatory diseases 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 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 and

  9. 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 into...

  10. The susceptibility of plasma coagulation factor XI to nitration and peroxynitrite action.

    Science.gov (United States)

    Ponczek, Michał Błażej

    2016-10-01

    Coagulation factor XI is present in blood plasma as the zymogen, like other serine proteases of hemostatic system, but as the only coagulation factor forms 140-160kDa homodimers. Its activation is induced by thrombin, and a positive feedback increases the generation of the extra thrombin. Experimental and clinical observations confirm protective roles of factor XI deficiencies in certain types of thromboembolic disorders. Thromboembolism still causes serious problems for modern civilization. Diseases associated with the blood coagulation system are often associated with inflammation and oxidative stress. Peroxynitrite is produced from nitric oxide and superoxide in inflammatory diseases. The aim of the current study is to evaluate effects of nitrative stress triggered by peroxynitrite on coagulation factor XI in human plasma employing biochemical and bioinformatic methods. The amidolytic assay shows increase in factor XI activity triggered by peroxynitrite. Peroxynitrite interferes factor XI by nitration and fragmentation, which is demonstrated by immunoprecipitation followed by western blotting. Nitrated factor XI is even present in control blood plasma. The results suggest possible modifications of factor XI on the molecular level. Computer simulations show tyrosine residues as targets of peroxynitrite action. The modifications induced by peroxynitrite in factor XI might be important in thrombotic disorders. PMID:27268383

  11. Coagulation factor deficiency apparently related to the Fitzgerald trait: the first cases in Japan.

    Directory of Open Access Journals (Sweden)

    Hayashi,Hisamoto

    1978-04-01

    Full Text Available A blood coagulation deficiency was found at the contact phase in identical Japanese female twins. Of the four possible factors involved, Factor XI or XII can be ruled out according to cross-correction studies. The problem factor was probably not Fletcher factor, because the abnormal partial thromboplastin time was not significantly shortened by increasing the incubation period of plasma with kaolin. The deficiency is most likely due to the lack of Fitzgerald factor.

  12. Study on Blood Coagulant/Fibrinolytic Activity at Plasma andMonocytic Levels in Coronary Heart Disease Patients withBlood-Stasis Syndrome of Traditional Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To explore and compare the changes of coagulant/fibrinolytic activity in coronary heart disease (CHD) patients with Blood Stasis Syndrome of TCM and evaluate the roles of these changes. Methods: Eighty patients of CHD were divided into two groups by Syndrome Differentiation of TCM, the Blood-Stasis (BS) group (30 cases) and the non-Blood-Stasis (NBS) group (50 cases, including 27 cases of Phlegm-Dampness Syndrome and 23 cases of Qi-Stagnation Syndrome); and 20 healthy persons were enrolled as normal control group. Tissue type plasminogen activator (t-PA) and its inhibitor (PAI-1) in plasma and in human peripheral blood monocyte cell (PBMC), as well as the procoagulant activity (PCA) in PBMC were measured by chromogenic substrate method. Results: The plasma PAI-1 activity and PCA of PBMC in the BS group were significantly higher than those in the NBS group and the normal control group (P<0.01). PAI-1 activity of PBMC in the two groups of CHD patients was higher than those in the normal control group significantly (P<0.01), but no significant difference was found between the BS group and the NBS group (P>0.05). The difference of plasma t-PA activity between the two groups of CHD was insignificant. The PBMC t-PA activity in the BS group was lower than that in the NBS and normal control groups (P<0.01). Conclusion: In the CHD patients with BS, the PBMC PCA was increased and the fibrinolytic activity at both plasma and monocyte levels lowered significantly, these changes in coagulant/fibrinolytic activity may be the important pathologic factors in forming BS which suggests that CHD patients with BS were in the prothrombotic state.

  13. Nonsense-mediated mRNA decay among coagulation factor genes

    Directory of Open Access Journals (Sweden)

    Shirin Shahbazi

    2016-04-01

    Full Text Available Objective(s: Haemostasis prevents blood loss following vascular injury. It depends on the unique concert of events involving platelets and specific blood proteins, known as coagulation factors. The clotting system requires precise regulation and coordinated reactions to maintain the integrity of the vasculature. Clotting insufficiency mostly occurs due to genetically inherited coagulation factor deficiencies such as hemophilia. Materials and Methods: A relevant literature search of PubMed was performed using the keywords coagulation factors, Nonsense-mediated mRNA decay and premature translation termination codons. Search limitations included English language and human-based studies. Results: Mutations that cause premature translation termination codons probably account for one-third of genetically inherited diseases. Transcripts bearing aberrant termination codons are selectively identified and eliminated by an evolutionarily conserved posttranscriptional pathway known as nonsense-mediated mRNA decay (NMD. There are many pieces of evidence of decay among coagulation factor genes. However, the hemophilia gene (F8 does not seem to be subjected to NMD. Since the F8 gene is located on the X-chromosome, a connection between X-linked traits and mRNA decay could be assumed. Conclusion: Considering that not all genes go through decay, this review focuses on the basics of the mechanism in coagulation genes. It is interesting to determine whether this translation-coupled surveillance system represents a general rule for the genes encoding components of the same physiological cascade.

  14. Surface-mediated molecular events in material-induced blood-plasma coagulation

    Science.gov (United States)

    Chatterjee, Kaushik

    Coagulation and thrombosis persist as major impediments associated with the use of blood-contacting medical devices. We are investigating the molecular mechanism underlying material-induced blood-plasma coagulation focusing on the role of the surface as a step towards prospective development of improved hemocompatible biomaterials. A classic observation in hematology is that blood/blood-plasma in contact with clean glass surface clots faster than when in contact with many plastic surfaces. The traditional biochemical theory explaining the underlying molecular mechanism suggests that hydrophilic surfaces, like that of glass, are specific activators of the coagulation cascade because of the negatively-charged groups on the surface. Hydrophobic surfaces are poor procoagulants or essentially "benign" because they lack anionic groups. Further, these negatively-charged surfaces are believed to not only activate blood factor XII (FXII), the key protein in contact activation, but also play a cofactor role in the amplification and propagation reactions that ultimately lead to clot formation. In sharp contrast to the traditional theory, our investigations indicate a need for a paradigm shift in the proposed sequence of contact activation events to incorporate the role of protein adsorption at the material surfaces. These studies have lead to the central hypothesis for this work proposing that protein adsorption to hydrophobic surfaces attenuates the contact activation reactions so that poorly-adsorbent hydrophilic surfaces appear to be stronger procoagulants relative to hydrophobic surfaces. Our preliminary studies measuring the plasma coagulation response of activated FXII (FXIIa) on different model surfaces suggested that the material did not play a cofactor role in the processing of this enzyme dose through the coagulation pathway. Therefore, we focused our efforts on studying the mechanism of initial production of enzyme at the procoagulant surface. Calculations for the

  15. Coagulation-induced shedding of platelet glycoprotein VI mediated by factor Xa.

    Science.gov (United States)

    Al-Tamimi, Mohammad; Grigoriadis, George; Tran, Huy; Paul, Eldho; Servadei, Patricia; Berndt, Michael C; Gardiner, Elizabeth E; Andrews, Robert K

    2011-04-01

    This study evaluated shedding of the platelet collagen receptor, glycoprotein VI (GPVI) in human plasma. Collagen or other ligands induce metalloproteinase-mediated GPVI ectodomain shedding, generating approximately 55-kDa soluble GPVI (sGPVI) and approximately 10-kDa platelet-associated fragments. In the absence of GPVI ligands, coagulation of platelet-rich plasma from healthy persons induced GPVI shedding, independent of added tissue factor, but inhibitable by metalloproteinase inhibitor, GM6001. Factor Xa (FXa) common to intrinsic and tissue factor-mediated coagulation pathways was critical for sGPVI release because (1) shedding was strongly blocked by the FXa-selective inhibitor rivaroxaban but not FIIa (thrombin) inhibitors dabigatran or hirudin; (2) Russell viper venom that directly activates FX generated sGPVI, with complete inhibition by enoxaparin (inhibits FXa and FIIa) but not hirudin; (3) impaired GPVI shedding during coagulation of washed platelets resuspended in FX-depleted plasma was restored by adding purified FX; and (4) purified FXa induced GM6001-inhibitable GPVI shedding from washed platelets. In 29 patients with disseminated intravascular coagulation, mean plasma sGPVI was 53.9 ng/mL (95% confidence interval, 39.9-72.8 ng/mL) compared with 12.5 ng/mL (95% confidence interval, 9.0-17.3 ng/mL) in thrombocytopenic controls (n = 36, P coagulation-induced GPVI shedding via FXa down-regulates GPVI under procoagulant conditions. FXa inhibitors have an unexpected role in preventing GPVI down-regulation.

  16. Tissue Factor/Factor FVII Complex Inhibitors in Cardiovascular Disease. Are Things Going Well?

    OpenAIRE

    Petrillo, Gianluca; Cirillo, Plinio; D’Ascoli, Greta-Luana; Maresca, Fabio; Ziviello, Francesca; Chiariello, Massimo

    2010-01-01

    Blood coagulation is a complex biological mechanism aimed to avoid bleeding in which a highly regulated and coordinated interplay of specific proteins and cellular components respond quickly to a vascular injury. However, when this mechanisms occurs in the coronary circulation, it has not a “protective” effect, but rather, it plays a pivotal role in determining acute coronary syndromes. Coagulation recognizes Tissue Factor (TF), the main physiological initiator of the extrinsic coagulation pa...

  17. A Comparison Study of the Effects Injectable Contraceptive Cyclofem on Blood Coagulation and Fibrinolysis

    Institute of Scientific and Technical Information of China (English)

    孙丹利; 卢凤英; 陈爱军; 沈康元; 蒋海瑛; 童琮

    1995-01-01

    Forty-six healthy women received Cyclofem (25mg medroxyprogesterone acetate with 5mg estradiol cypionate) and other forty-five women, as control, received oral contraceptive pill (Orttm-Novum 1/35, containing norethisterone enantate 1mg and estradiol valerate 35μg) for nine months. Blood samples were taken during the follicular and luteal phases of pre- treatment, and for Cyclofem group, immediately prior to the 3rd and 9th injections and 1 and 3 weeks after the 3rd and 9th injections; for Ortho-Novum group, blood samples were taken on the irst day of the 3rd and 9th pill cycles and 1 and 3 weeks later in both cycles. For both groups after at least 3 months nonhormonal method of contraception, blood sampling was repeated at follicular and luteal phases of a normal mentrual cycle. Coagulation and fibrinolysis parameter were detected including hemoglobin, platelet count, prothrombin time, APTT, fibrinogen, factor Ⅶ, factor Ⅹ, plasminogen, t-PAL AT Ⅲ(functional and immunological assays) and protein C. In the Cyclofem group, hemoglobin, platelet count, fibrinogen and factor Ⅹ were not changed. Factor Ⅶ significantly reduced. Prothrombin time and APTT showed minor changes. Plasminogen and protein C decreased while t-PAI aad AT Ⅲ increased. These changes showed a dynamic balance between coagulation and fibrinolysis. In Ortho-Novum 1/35 group, platelet count, factor Ⅹ and fibrinogen increased and prothrombin time and APTT accelerated. In fibrinolysis and anticoagutation system, plasminogen increased as well as protein C, but AT Ⅲ declined. Those changes showed a tendency of hyper-eoagutability state, fibrinolysis and anticoagulation were enhanced to a certain extent.The result of our study is that there are slight changes on coagulation and fibrinolysis in Cyclofem injectable contraceptive users.

  18. Role of Hydrophobic Mutations on the Binding Affinity and Stability of Blood Coagulation Factor VIIIa: A Computational Molecular Dynamics and Free-Energy Analysis

    OpenAIRE

    Venkateswarlu, Divi

    2014-01-01

    Factor VIIIa is a non-covalently bound hetero-trimer among A1, A2 and A3-C1-C2 domains and an essential co-factor for factor IXa enzyme during proteolytic activation of factor X zymogen. The relatively weak interactions between A2 and the interface A1/A3 domains dampen the functional stability of FVIIIa in plasma and results in rapid degradation. We studied the mutational effect of three charged residues (Asp519, Glu665 and Asp666) to several hydrophobic residues by molecular dynamics simulat...

  19. Mesoscopic Modeling of Blood Clotting: Coagulation Cascade and Platelets Adhesion

    Science.gov (United States)

    Yazdani, Alireza; Li, Zhen; Karniadakis, George

    2015-11-01

    The process of clot formation and growth at a site on a blood vessel wall involve a number of multi-scale simultaneous processes including: multiple chemical reactions in the coagulation cascade, species transport and flow. To model these processes we have incorporated advection-diffusion-reaction (ADR) of multiple species into an extended version of Dissipative Particle Dynamics (DPD) method which is considered as a coarse-grained Molecular Dynamics method. At the continuum level this is equivalent to the Navier-Stokes equation plus one advection-diffusion equation for each specie. The chemistry of clot formation is now understood to be determined by mechanisms involving reactions among many species in dilute solution, where reaction rate constants and species diffusion coefficients in plasma are known. The role of blood particulates, i.e. red cells and platelets, in the clotting process is studied by including them separately and together in the simulations. An agonist-induced platelet activation mechanism is presented, while platelets adhesive dynamics based on a stochastic bond formation/dissociation process is included in the model.

  20. Thrombin Inhibitors from Different Animals

    OpenAIRE

    Tanaka-Azevedo, A. M.; Morais-Zani, K.; Torquato, R. J. S.; A. S. Tanaka

    2010-01-01

    Venous and arterial thromboembolic diseases are still the most frequent causes of death and disability in high-income countries. Clinical anticoagulants are inhibitors of enzymes involved in the coagulation pathway, such as thrombin and factor Xa. Thrombin is a key enzyme of blood coagulation system, activating the platelets, converting the fibrinogen to the fibrin net, and amplifying its self-generation by the activation of factors V, VIII, and XI. Thrombin has long been a target for the dev...

  1. Quality Control and Assurance for Coagulation Tests

    Institute of Scientific and Technical Information of China (English)

    彭黎明

    2006-01-01

    @@ The coagulation laboratory aids the clinician in assessing not only the bleeding patient but also the thrombotic patient. The techniques of coagulation laboratory are used to evaluate not only the coagulation system but also the anti-coagulation system, fibrinolytic system,platelet and vascular endothelial function. Enzymes, inhibitors, plasma factors and co-factors, cellular release products, and cell receptors can be measured in coagulation laboratory.

  2. PLATELET-LEUKOCYTE INTERACTIONS : MULTIPLE LINKS BETWEEN INFLAMMATION , BLOOD COAGULATION AND VASCULAR RISK

    Directory of Open Access Journals (Sweden)

    Chiara Cerletti

    2010-08-01

    Full Text Available The aim of this review is to summarize the contribution of platelets and leukocytes and their interactions in inflammation and blood coagulation and its possible relevance in the pathogenesis of  thrombosis. There is some evidence of an association between infection/inflammation and thrombosis. This is likely a bidirectional relationship. The presence of a thrombus may serve as a nidus of infection. Vascular injury indeed promotes platelet and leukocyte activation and thrombus formation and the thrombus and its components facilitate adherence of bacteria to the vessel wall. Alternatively, an infection and the associated inflammation can trigger platelet and leukocyte activation and thrombus formation. In either case platelets and leukocytes co-localize and interact in the area of vascular injury, at sites of inflammation and/or at sites of thrombosis. Following vascular injury, the subendothelial tissue, a thrombogenic surface, becomes available for interaction with these blood cells. Tissue factor, found not only in media and adventitia of the vascular wall, but also on activated platelets and leukocytes, triggers blood coagulation. Vascular-blood cell interactions, mediated by the release of preformed components of the endothelium, is modulated by both cell adhesion and production of soluble stimulatory or inhibitory molecules that alter cell function: adhesion molecules regulate cell-cell contact and facilitate the modulation of biochemical pathways relevant to inflammatory and/or thrombotic processes.

  3. 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.

  4. Role of hydrophobic mutations on the binding affinity and stability of blood coagulation factor VIIIa: a computational molecular dynamics and free-energy analysis.

    Science.gov (United States)

    Venkateswarlu, Divi

    2014-07-18

    Factor VIIIa is a non-covalently bound hetero-trimer among A1, A2 and A3-C1-C2 domains and an essential co-factor for factor IXa enzyme during proteolytic activation of factor X zymogen. The relatively weak interactions between A2 and the interface A1/A3 domains dampen the functional stability of FVIIIa in plasma and results in rapid degradation. We studied the mutational effect of three charged residues (Asp519, Glu665 and Asp666) to several hydrophobic residues by molecular dynamics simulations. Analysis of the binding free energy by MM-PBSA and MM-GBSA methods shows that the mutation of Asp519 and Glu665 residues to either Val or Ala enhance the A2 domain binding affinity in agreement with the experimental site-specific mutagenesis data. Mutation of Asp666 to Val, Tyr, Met and Phe showed largest improvement in the A2-domain binding among the eight hydrophobic mutants studied. Our studies suggest that the enrichment of hydrophobic interactions in the buried surface regions of A2 domain plays crucial role in improving the overall stability of FVIIIa. PMID:24952158

  5. 慢性荨麻疹与凝血机制的研究进展%Chronic urticaria and blood coagulation mechanism

    Institute of Scientific and Technical Information of China (English)

    王朵勤; 唐慧; 徐金华

    2011-01-01

    Blood coagulation plays an important role in the pathogenesis of chronic urticaria. Both the intrinsic and extrinsic pathways of the coagulation cascade are activated in chronic urticaria, which in turn induce the generation of thrombin. Thrombin, as the agonist of proteinase-activated receptors, can induce histamine release from mast cells, and then cause the development of urticaria. The severity of urticaria is parallel to the quantity of coagulation factors. Anticoagulants and protease inhibitors have shown certain efficacy in the treatment of some refractory urticaria. This paper summarizes recent progress in the development of blood coagulation-targeting strategies for the treatment of chronic urticaria.%凝血机制在慢性荨麻疹的发病中起着重要的作用。内、外源性凝血途径同时被激活,产生凝血酶。凝血酶是一种蛋白酶激活受体激动剂,可诱导肥大细胞释放组胺,从而诱发荨麻疹的发生。其病情严重性随着凝血因子数量的增高而加重。抗凝药物及蛋白酶抑制剂对部分难治性荨麻疹有一定疗效。概述近几年针对凝血机制治疗慢性荨麻疹的研究进展。

  6. Analysis of the coagulation of human blood cells on diamond surfaces by atomic force microscopy

    Science.gov (United States)

    Baranauskas, V.; Fontana, M.; Guo, Zhao Jing; Ceragioli, H. J.; Peterlevitz, A. C.

    2004-11-01

    Atomic force microscopy (AFM) was used to study the morphology and coagulation of human blood cells in contact with solid surfaces. Blood was extracted from the veins of healthy adult donors and the samples were used immediately after extraction, deposited either on borosilicate glass or diamond substrates. Some blood samples were anti-coagulated by adding heparin for single cell AFM imaging. No chemicals were used for attaching or immobilizing the cells. The diamond substrates were produced by chemical vapour deposition (CVD diamond) using a hot-filament CVD system fed with ethanol highly diluted in hydrogen. AFM imaging of isolated cells (anti-coagulated by heparin) was only possible on the glass substrates due to the lack of adherence of the cells to the diamond surface. The coagulation results suggest that blood clotting on diamond produces a less rough surface than blood clotting on glass.

  7. 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

    with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACI), improves survival in a lethal model of cecal ligation and puncture (CLP) in mice, but its effect on coagulation remains unknown. The goal of this study was to quantify the impact of SAHA treatment on coagulopathy in sepsis. METHODS...

  8. 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. PMID:27114461

  9. Contact activation of blood coagulation on a defined kaolin/collagen surface in a microfluidic assay

    OpenAIRE

    Zhu, Shu; Diamond, Scott L.

    2014-01-01

    Generation of active Factor XII (FXIIa) triggers blood clotting on artificial surfaces and may also enhance intravascular thrombosis. We developed a patterned kaolin (0 to 0.3 pg/μm2)/type 1 collagen fibril surface for controlled microfluidic clotting assays. Perfusion of whole blood (treated only with a low level of 4 μg/mL of the XIIa inhibitor, corn trypsin inhibitor) drove platelet deposition followed by fibrin formation. At venous wall shear rate (100 s−1), kaolin accelerated onset of fi...

  10. Metalloproteases Affecting Blood Coagulation, Fibrinolysis and Platelet Aggregation from Snake Venoms: Definition and Nomenclature of Interaction Sites

    Science.gov (United States)

    Kini, R. Manjunatha; Koh, Cho Yeow

    2016-01-01

    Snake venom metalloproteases, in addition to their contribution to the digestion of the prey, affect various physiological functions by cleaving specific proteins. They exhibit their activities through activation of zymogens of coagulation factors, and precursors of integrins or receptors. Based on their structure–function relationships and mechanism of action, we have defined classification and nomenclature of functional sites of proteases. These metalloproteases are useful as research tools and in diagnosis and treatment of various thrombotic and hemostatic conditions. They also contribute to our understanding of molecular details in the activation of specific factors involved in coagulation, platelet aggregation and matrix biology. This review provides a ready reference for metalloproteases that interfere in blood coagulation, fibrinolysis and platelet aggregation. PMID:27690102

  11. [The effects of Arnica Montana on blood coagulation. Randomized controlled trial].

    Science.gov (United States)

    Baillargeon, L; Drouin, J; Desjardins, L; Leroux, D; Audet, D

    1993-11-01

    The purpose of this study, which took the form of a two-period cross-over clinical trial, was to determine whether a homeopathic substance, Arnica Montana, significantly decreased bleeding time (Simplate II) and to describe its impact on various blood coagulation tests. It was not shown that this substance had a significant impact on various parameters of blood coagulation in healthy volunteers in the period immediately following administration [corrected].

  12. 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.

  13. EPCR-dependent PAR2 activation by the blood coagulation initiation complex regulates LPS-triggered interferon responses in mice.

    Science.gov (United States)

    Liang, Hai Po H; Kerschen, Edward J; Hernandez, Irene; Basu, Sreemanti; Zogg, Mark; Botros, Fady; Jia, Shuang; Hessner, Martin J; Griffin, John H; Ruf, Wolfram; Weiler, Hartmut

    2015-04-30

    Infection and inflammation are invariably associated with activation of the blood coagulation mechanism, secondary to the inflammation-induced expression of the coagulation initiator tissue factor (TF) on innate immune cells. By investigating the role of cell-surface receptors for coagulation factors in mouse endotoxemia, we found that the protein C receptor (ProcR; EPCR) was required for the normal in vivo and in vitro induction of lipopolysaccharide (LPS)-regulated gene expression. In cultured bone marrow-derived myeloid cells and in monocytic RAW264.7 cells, the LPS-induced expression of functionally active TF, assembly of the ternary TF-VIIa-Xa initiation complex of blood coagulation, and the EPCR-dependent activation of protease-activated receptor 2 (PAR2) by the ternary TF-VIIa-Xa complex were required for the normal LPS induction of messenger RNAs encoding the TLR3/4 signaling adaptor protein Pellino-1 and the transcription factor interferon regulatory factor 8. In response to in vivo challenge with LPS, mice lacking EPCR or PAR2 failed to fully initiate an interferon-regulated gene expression program that included the Irf8 target genes Lif, Iigp1, Gbp2, Gbp3, and Gbp6. The inflammation-induced expression of TF and crosstalk with EPCR, PAR2, and TLR4 therefore appear necessary for the normal evolution of interferon-regulated host responses.

  14. Blood Coagulation Induced by Iranian Saw-Scaled Viper (Echis Carinatus) Venom: Identification, Purification and Characterization of a Prothrombin Activator

    OpenAIRE

    Mahdi Babaie; Hossein Salmanizadeh; Hossein Zolfagharian

    2013-01-01

      Objective(s): Echis carinatus is one of the venomous snakes in Iran. The venom of Iranian Echis carinatus is a rich source of protein with various factors affecting the plasma protein and blood coagulation factor. Some of these proteins exhibit types of enzymatic activities. However, other items are proteins with no enzymatic activity.   Materials and Methods: In order to study the mechanism and effect of the venom on human plasma proteins, the present study has evaluated the effect of crud...

  15. 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.

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

    International Nuclear Information System (INIS)

    Our previous work demonstrated that an optical coherence tomography (OCT) technique and the parameter 1/e light penetration depth (d1/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 d1/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)

  17. The Levels of Tissue Factor Pathway Inhibitor in Sepsis Patients Receiving Prophylactic Enoxaparin

    Directory of Open Access Journals (Sweden)

    Hadil A. Al Otair

    2016-05-01

    Full Text Available Objective: Sepsis syndrome is usually accompanied by activation of blood coagulation mechanisms. Earlier studies found deficiencies of the 3 main natural anticoagulants, antithrombin, protein C, and protein S. However, none of these inhibitors block tissue factor, the prime trigger of coagulation during sepsis that is controlled specifically by the tissue factor pathway inhibitor (TFPI. The aim of this study was to characterize the fluctuations in the levels of natural anticoagulants, particularly TFPI, in the course of sepsis and to find out their association with the anticoagulant action of the lowmolecular-weight heparin enoxaparin. Materials and Methods: We studied 51 consecutive patients with sepsis. Blood samples were collected from patients at baseline (0 h and at 4, 12, and 24 h after enoxaparin administration. The following assays were undertaken using commercial kits: activated partial thromboplastin time, prothrombin time, thrombin time, total and free TFPI, protein C and protein S, antithrombin, fibrinogen, and anti-factor Xa. Results: Before enoxaparin administration, there was significant prolongation of the prothrombin time and activated partial thromboplastin time, and this remained the case in the 3 subsequent samples. There was marked reduction in the levels of antithrombin, protein C, and total and free protein S to below control values throughout the study. In contrast, plasma levels of both total and free TFPI were markedly elevated and increased after enoxaparin therapy. Anti-factor Xa levels were within the therapeutic range throughout. There was no difference in TFPI levels between those patients who died and those who survived. Conclusion: Sepsis triggered marked release of TFPI from endothelial cells. This persisted and was increased further following the administration of enoxaparin. In contrast, there was marked consumption of the natural coagulation inhibitors antithrombin, protein C, and protein S. These results go

  18. Platelet surface-associated activation and secretion-mediated inhibition of coagulation factor XII.

    Science.gov (United States)

    Zakharova, Natalia V; Artemenko, Elena O; Podoplelova, Nadezhda A; Sveshnikova, Anastasia N; Demina, Irina A; Ataullakhanov, Fazly I; Panteleev, Mikhail A

    2015-01-01

    Coagulation factor XII (fXII) is important for arterial thrombosis, but its physiological activation mechanisms are unclear. In this study, we elucidated the role of platelets and platelet-derived material in fXII activation. FXII activation was only observed upon potent platelet stimulation (with thrombin, collagen-related peptide, or calcium ionophore, but not ADP) accompanied by phosphatidylserine exposure and was localised to the platelet surface. Platelets from three patients with grey platelet syndrome did not activate fXII, which suggests that platelet-associated fXII-activating material might be released from α-granules. FXII was preferentially bound by phosphotidylserine-positive platelets and annexin V abrogated platelet-dependent fXII activation; however, artificial phosphotidylserine/phosphatidylcholine microvesicles did not support fXII activation under the conditions herein. Confocal microscopy using DAPI as a poly-phosphate marker did not reveal poly-phosphates associated with an activated platelet surface. Experimental data for fXII activation indicates an auto-inhibition mechanism (ki/ka = 180 molecules/platelet). Unlike surface-associated fXII activation, platelet secretion inhibited activated fXII (fXIIa), particularly due to a released C1-inhibitor. Platelet surface-associated fXIIa formation triggered contact pathway-dependent clotting in recalcified plasma. Computer modelling suggests that fXIIa inactivation was greatly decreased in thrombi under high blood flow due to inhibitor washout. Combined, the surface-associated fXII activation and its inhibition in solution herein may be regarded as a flow-sensitive regulator that can shift the balance between surface-associated clotting and plasma-dependent inhibition, which may explain the role of fXII at high shear and why fXII is important for thrombosis but negligible in haemostasis. PMID:25688860

  19. Platelet surface-associated activation and secretion-mediated inhibition of coagulation factor XII.

    Directory of Open Access Journals (Sweden)

    Natalia V Zakharova

    Full Text Available Coagulation factor XII (fXII is important for arterial thrombosis, but its physiological activation mechanisms are unclear. In this study, we elucidated the role of platelets and platelet-derived material in fXII activation. FXII activation was only observed upon potent platelet stimulation (with thrombin, collagen-related peptide, or calcium ionophore, but not ADP accompanied by phosphatidylserine exposure and was localised to the platelet surface. Platelets from three patients with grey platelet syndrome did not activate fXII, which suggests that platelet-associated fXII-activating material might be released from α-granules. FXII was preferentially bound by phosphotidylserine-positive platelets and annexin V abrogated platelet-dependent fXII activation; however, artificial phosphotidylserine/phosphatidylcholine microvesicles did not support fXII activation under the conditions herein. Confocal microscopy using DAPI as a poly-phosphate marker did not reveal poly-phosphates associated with an activated platelet surface. Experimental data for fXII activation indicates an auto-inhibition mechanism (ki/ka = 180 molecules/platelet. Unlike surface-associated fXII activation, platelet secretion inhibited activated fXII (fXIIa, particularly due to a released C1-inhibitor. Platelet surface-associated fXIIa formation triggered contact pathway-dependent clotting in recalcified plasma. Computer modelling suggests that fXIIa inactivation was greatly decreased in thrombi under high blood flow due to inhibitor washout. Combined, the surface-associated fXII activation and its inhibition in solution herein may be regarded as a flow-sensitive regulator that can shift the balance between surface-associated clotting and plasma-dependent inhibition, which may explain the role of fXII at high shear and why fXII is important for thrombosis but negligible in haemostasis.

  20. 重组腺相关病毒2型/人凝血因子IX的质量研究%Quality control of recombinant adeno-associated virus type 2/human blood coagulation factor IX

    Institute of Scientific and Technical Information of China (English)

    高凯; 王军志; 饶春明; 吴小兵

    2003-01-01

    目的研究并建立重组腺相关病毒2型/人凝血因子IX(recombinant adeno-associated virus type 2/human blood coagulation factor IX,rAAV-2/hFIX)的质量标准.方法采用PCR法确认病毒所携带的重组核酸结构和测定辅助病毒(helper virus)和野生型腺相关病毒(wtAAV)的残留片段.SDS-PAGE电泳测定病毒外壳蛋白分子量及纯度,TSK gel SP-NPR阳离子交换柱系统测定病毒颗粒纯度.以斑点杂交法测定病毒颗粒数.一期法于IX因子基因剔除小鼠体内测定rAAV-2/hFIX生物学活性,并通过ELISA法测定感染BHK-21细胞后hFIX的表达量.结果 PCR法确证病毒的重组核酸结构与构建预期相同;在1×107 VG的rAAV-2/hFIX颗粒中,残留辅助病毒的基因片段数少于1个拷贝;在1×108 VG的rAAV-2/hFIX颗粒中,野生型AAV-2基因片段数少于1个拷贝.病毒颗粒及外壳蛋白纯度均大于98%,病毒颗粒数大于1.0×1015 VG*L-1(virus genome*L-1).IX因子剔除小鼠肌肉注射病毒后21 d,小鼠血液中人凝血因子IX活性达到大于正常人因子IX活性的15%,IX因子的体外表达水平大于20.0 μg*L-1.其他各项检测指标均符合规定.结论建立了rAAV-2/hFIX的质量标准,用于控制产品质量.

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

    Directory of Open Access Journals (Sweden)

    Manash S Chatterjee

    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

  2. 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

  3. Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid carriers and complement factors induced by oral contraceptives

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Poulsen, Henning Kvist; Teisner, Børge;

    1993-01-01

    Three low-dose oral contraceptives Trinordiol, Gynatrol, and Marvelon, containing ethinylestradiol (EE) in combination with triphasic levonorgestrel (LNg), monophasic levonorgestrel, and monophasic desogestrel (DGS), respectively, were given to 65 healthy women, n = 21-22 in each group. Blood...

  4. 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.

  5. [Basic values of blood coagulation parameters in pigs (Sus scrofa domesticus)].

    Science.gov (United States)

    Hahn, N; Popov-Cenic, S; Dorer, A

    1996-01-01

    On 23 clinical healthy pigs (2-4 months of age, body weight 13-42 kg) under ketamin-pentobarbital anaesthesia blood plasma coagulation parameters have been investigated. To obtain basic values 26 parameters were measured: number of thrombocytes, parameters of thrombelastogram and resonance-thrombogram, prothrombin time, activated partial thromboplastin time, thrombin time, reptilase time, factors I, II, V, VII, VIII, X, antithrombin III, plasminogen, alpha 1-antitrypsin, alpha 2-antiplasmin, alpha 2-macroglobulin, fibrin degradation products D and E and euglobulin lysis-time. Parameters calculated in percent should be measured against a pig plasma pool. Measurement against a human plasma pool are hardly valid in values higher than 100%. In comparison to man the results indicate modifications of fibrinogenesis and fibrinolysis in pigs.

  6. Thrombin generation by exposure of blood to endotoxin: a simple model to study disseminated intravascular coagulation.

    Science.gov (United States)

    Stief, T W

    2006-04-01

    Pathologic disseminated intravascular coagulation (PDIC) is a serious complication in sepsis. In an in-vitro system consisting of incubation of fresh citrated blood with lipopolysaccharides (LPS) or glucans and subsequent plasma recalcification plasmatic thrombin was quantified. Five hundred microliters of freshly drawn citrated blood of healthy donors were incubated with up to 800 ng/mL LPS (Escherichia coli) or up to 80 microg/mL Zymosan A (ZyA; Candida albicans) for 30 minutes at room temperature (RT). The samples were centrifuged, and 30 microL plasma were recalcified with 1 volume or less of CaCl(2) (25 micromoles Ca(2+)/mL plasma). After 0 to 12 minutes (37 degrees C), 20 microL 2.5 M arginine, pH 8.6, were added. Thirty microliters 0.9 mM HD-CHG-Ala-Arg-pNA in 2.3 M arginine were added, and the absorbance increase at 405 nm was determined. Fifty microliters plasma were also incubated with 5 microL 250 mM CaCl2 for 5, 10, or 15 minutes (37 degrees C). Fifty microliters 2.5 M arginine stops coagulation, and 50 microL 0.77 mM HD-CHG-Ala-Arg-pNA in 2.3 M arginine starts the thrombin detection. The standard was 1 IU/mL thrombin in 7% human albumin instead of plasma. Arginine was also added in the endotoxin exposure time (EET) or in the plasma coagulation reaction time (CRT). Tissue factor (TF)-antigen and soluble CD14 were determined. LPS at blood concentrations greater than 10 ng/mL or ZyA at greater than 1 microg/mL severalfold enhance thrombin generation, when the respective plasmas are recalcified. After 30 minutes EET at RT, the thrombin activity at 12 minutes CRT generated by the addition of 200 ng/mL LPS or 20 microg/mL ZyA is approximately 200 mIU/mL compared to approximately 20 mIU/mL without addition of endotoxin, or compared to about 7 mIU/mL thrombin at 0 minutes CRT. Arginine added to blood or to plasma inhibits thrombin generation; the inhibitory concentration 50% (IC 50) is approximately 15 mM plasma concentration. Endotoxin incubation of blood

  7. Dynamic and quantitative assessment of blood coagulation using optical coherence elastography

    Science.gov (United States)

    Xu, Xiangqun; Zhu, Jiang; Chen, Zhongping

    2016-04-01

    Reliable clot diagnostic systems are needed for directing treatment in a broad spectrum of cardiovascular diseases and coagulopathy. Here, we report on non-contact measurement of elastic modulus for dynamic and quantitative assessment of whole blood coagulation using acoustic radiation force orthogonal excitation optical coherence elastography (ARFOE-OCE). In this system, acoustic radiation force (ARF) is produced by a remote ultrasonic transducer, and a shear wave induced by ARF excitation is detected by the optical coherence tomography (OCT) system. During porcine whole blood coagulation, changes in the elastic property of the clots increase the shear modulus of the sample, altering the propagating velocity of the shear wave. Consequently, dynamic blood coagulation status can be measured quantitatively by relating the velocity of the shear wave with clinically relevant coagulation metrics, including reaction time, clot formation kinetics and maximum shear modulus. The results show that the ARFOE-OCE is sensitive to the clot formation kinetics and can differentiate the elastic properties of the recalcified porcine whole blood, blood added with kaolin as an activator, and blood spiked with fibrinogen.

  8. Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid carriers and complement factors induced by oral contraceptives

    DEFF Research Database (Denmark)

    Nielsen, C H; Poulsen, H K; Teisner, B;

    1993-01-01

    Three low-dose oral contraceptives Trinordiol, Gynatrol, and Marvelon, containing ethinylestradiol (EE) in combination with triphasic levonorgestrel (LNg), monophasic levonorgestrel, and monophasic desogestrel (DGS), respectively, were given to 65 healthy women, n = 21-22 in each group. Blood lev...

  9. Assessment of blood coagulation under various flow conditions with ultrasound backscattering.

    Science.gov (United States)

    Huang, Chih-Chung; Wang, Shyh-Hau

    2007-12-01

    Several in vitro studies have employed ultrasonic techniques to detect varying properties of coagulating blood under static or stirred conditions. Most of those studies mainly addressed on the development and feasibility of modalities and however were not fully considering the effect of blood flow. To better elucidate this issue, ultrasonic backscattering were measured from the coagulating porcine blood circulated in a mock flow loop with various steady laminar flows at mean shear rates from 10 to 100 s(-1). A 3 ml of 0.5 M CaCl2 solution for inducing blood coagulation was added to that of 30 ml blood circulated in the conduit. For each measurement carried out with a 10-MHz transducer, backscattered signals digitized at 100-MHz sampling frequency were acquired for a total of 20 min at temporal resolution of 50 A-lines per s. The integrated backscatter (IB) was calculated for assessing backscattering properties of coagulating blood. The results show that blood coagulation tended to be increased corresponding to the addition of CaCl2 solution: the IB was increased approximately 6.1 +/- 0.6 (mean +/- standard deviation), 5.4 +/- 0.9, and 4.5 +/- 1.2 dB at 310 +/- 62, 420 +/- 88, and 610 +/- 102 s associated with mean shear rates of 10, 40, and 100 s(-1), respectively. The rate of increasing IB for evaluating the growth of clot was estimated to be 0.075 +/- 0.017, 0.052 +/- 0.027, and 0.038 +/- 0.012 delta dB delta s(-1) corresponding to the increase of mean shear rates. These results consistently demonstrate that higher shear rate tends to prolong the duration for the flowing blood to be coagulated and to decrease the rate of IB. Moreover, the laminar flow was changed to turbulent flow during that the blood was clotting discerned by spatial variations of ultrasound backscattering in the conduit. All these results validate that ultrasound backscattering is feasible to be utilized for detecting and assessing blood coagulation under dynamic conditions.

  10. Effect of magnetic bracelets on the coagulation and anticoagulation systems of the blood of patients with hypertension

    Science.gov (United States)

    Bublis, V. V.; Zabrodina, L. V.; Platonova, A. T.; Meyerova, Y. A.

    1974-01-01

    The data which have been obtained on the influence of magnetic bracelets on the coagulation and anticoagulation systems of the blood indicate that the wearing of magnetic bracelets results in a decrease in the coagulation activity of the blood and an increase in the activity of the anticoagulation system. These changes must be viewed as favorable for patients with cardiovascular pathology.

  11. Activation of Coagulation by Administration of Recombinant Factor VIIa Elicits Interleukin 6 (IL-6) and IL-8 Release in Healthy Human Subjects

    OpenAIRE

    de Jonge, Evert; Friederich, Philip W.; Vlasuk, George P.; Rote, William E.; Vroom, Margaretha B.; Levi, Marcel; van der Poll, Tom

    2003-01-01

    The activation of coagulation has been shown to contribute to proinflammatory responses in animal and in vitro experiments. Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma. This increase was absent when the subjects were pretreated with recombinant nematode anticoagulant protein c2, the inhibitor of tissue f...

  12. Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid carriers and complement factors induced by oral contraceptives

    DEFF Research Database (Denmark)

    Nielsen, C H; Poulsen, H K; Teisner, B;

    1993-01-01

    levels of antithrombin III (AT III), alpha 2-macroglobulin (alpha 2M) alpha 1-antitrypsin (alpha 1at), complement factors (factor B, C3, C4), pregnancy zone protein (PZP), corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG) and albumin were measured before treatment and during...... the first and third treatment cycles. AT III levels decreased and alpha 1at levels increased in all three groups during treatment. alpha 2M increased during cycle 3 in the Trinordiol and Gynatrol groups. CBG, PZP and SHBG levels increased in all 3 groups, the CBG and PZP increase being higher...... in the Marvelon group than in the Gynatrol group. Increases in SHBG levels were found in the order Marvelon > Trinordiol > Gynatrol. Plasma levels of complement factors B, C3 and C4 remained unchanged. It is concluded that the increase in alpha 1at partly compensates for the fall in AT III, that the rise in PZP...

  13. 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...... to investigate the effect of unfractionated heparin and TFPI, which is released from the endothelium by heparin, on FVII:C, FVIIa, and FVII:Ag. Heparin infusion decreased triglycerides and increased FFA and TFPI. This was accompanied by significant reductions in FVIIa, FVII:C and FVII:Ag. In vitro, anti...

  14. Effect of long-term hormone replacement therapy on tissue factor pathway inhibitor and thrombin activatable fibrinolysis inhibitor in healthy postmenopausal women: a randomized controlled study

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Madsen, J S; Kristensen, S R;

    2003-01-01

    arterial tissue factor expression and higher thrombin formation, and changes in tissue factor pathway coagulation inhibitor (TFPI) and thrombin activatable fibrinolysis inhibitor (TAFI) may be deleterious. Healthy postmenopausal women (n = 719) were randomized to hormone therapy [n = 357; opposed (n = 290...

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

    OpenAIRE

    Gavrilenko, M. A.

    2014-01-01

    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 hyg...

  16. Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro

    Institute of Scientific and Technical Information of China (English)

    Jing LI; Wei CAO; Xiao-xing LV; Li JIANG; Yue-jun LI; Wang-zhou LI; Shao-zong CHEN

    2013-01-01

    Aim:To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro.Methods:Fresh blood was taken from healthy adult volunteers and sheep,and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer.Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4,8,or 16 mL).The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy.The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method.The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer.Results:Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca2+ concentration,while Na+ and K+ concentrations were significantly decreased.Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca2+ and Na+ concentrations.Si4+ (0.2434 g/L) and Al3+ (0.2575 g/L) were detected in ZSS (2 g/8 mL).Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner,without changing PT.ZSS or aqueous solution of CaCl2 that contained Ca2+ concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR,and the effect of ZSS on ACT was not significantly different from that of CaCl2.Conclusion:Zeolite releases Ca2+ into blood,thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time.

  17. [Coagulation hemostasis and fibrinolytic potential of blood in conditions of chronic stress and terahertz therapy].

    Science.gov (United States)

    Kirichuk, V F; Tsymbal, A A; Antipova, O N; Tupikin, V D; Maĭborodin, A V; Krenitskiĭ, A P; Betskiĭ, O V

    2007-01-01

    The effects of electromagnetic rays of maximum high frequencies of radiation molecular spectrum and absorption of nitrogen oxide 150, 176-150, 664 GHz on blood coagulation properties of white laboratory rats subjected to chronic immobilization stress have been studied. It is shown that preventive course of electromagnetic irradiation with terahertz range at the frequencies of molecular spectrum of radiation and absorption of nitrogen oxide 150, 176-150, 664 GHz warns about development of stress disturbances of coagulation component of the hemostasis system and fibrinolysis in animals. PMID:17465273

  18. High levels of coagulation factor XI as a risk factor for venous thrombosis.

    NARCIS (Netherlands)

    Meijers, JCM; Tekelenburg, WLH; Bertina, RM; Rosendaal, FR; Bouma, Bonno N.

    2000-01-01

    Background: Factor XI, a component of the intrinsic pathway of coagulation, contributes to the generation of thrombin, which is involved in both the formation of fibrin and protection against fibrinolysis. A deficiency of factor XI is associated with bleeding, but a role of high factor XI levels in

  19. 人凝血因子Ⅸ的研究进展%Research progress in human coagulation factor

    Institute of Scientific and Technical Information of China (English)

    韩静静; 杨忠东

    2013-01-01

    Human coagulation factor Ⅸ (FⅨ) is a zymogen of a vitamin K-dependent serine protease that plays an important role in the intrinsic blood coagulation cascade.Deficiency or dysfunction of FⅨ can result in hemophilia B.This article reviews gene and protein structures of FⅨ as well as research status of FⅨ therapy for hemophilia B.%人凝血因子Ⅸ(human coagulation factor Ⅸ,FⅨ)是一种维生素K依赖性丝氨酸蛋白酶原,在内源性凝血级联反应中起重要作用.FⅨ缺乏或功能异常会导致血友病B.此文综述了FⅨ的基因和蛋白结构,以及FⅨ用于血友病B治疗的研究现状.

  20. 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.

  1. 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

  2. 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

  3. 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...... Kabi, Uppsala, Sweden) only a minor effect on coagulation competence is expected. METHODS: Eighty patients were scanned for enrollment in the study, and 40 patients fulfilled the inclusion criteria. Two patients withdrew their consent to participate in the study, and 5 patients were excluded. Thus, 16...... patients were randomized to receive lactated Ringer's solution and 17 to receive HES 130/0.4. RESULTS: Among the patients receiving HES 130/0.4, thrombelastography indicated reduced clot strength (P < 0.001) and blinded evaluation of the perioperative blood loss was 2.2 (range 0.5 to 5.0) versus 1.4 (range...

  4. Influence of low molecular heparin on blood coagulation function and lung function in AECOPD patients

    Institute of Scientific and Technical Information of China (English)

    Rui Deng

    2016-01-01

    Objective:To explore the influence of low molecular heparin on the blood coagulation function and lung function in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients.Methods:A total of 100 cases AECOPD patients were divided into observation group and control group according to the present order and odd number by half. They were all given AECOPD conventional symptomatic treatment, on this basis, patients in the observation group were treated with low molecular heparin, 10 d after treatment, arterial blood gas index such as oxygen partial pressure (PaO2), oxygen saturation (SaO2), carbon dioxide partial pressure (PaCO2), pulmonary function index such as forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), FEV1/FVC, blood coagulation function index such as fibrinogen (Fib), D-dimer (D-D), activated partial blood coagulation time (APTT) live enzymes, plasma prothrombin time (PT), thrombin time (TT) between two groups before and after treatment were compared.Results:Compared with before treatment, the levels of PaO2, SaO2, FEV1 and FVC, FEV1/FVC in control group after treatment were significantly elevated, PaCO2, D-D were significantly reduced, the difference were statistically significant (P<0.05); The levels of PaO2, SaO2, FEV1 and FVC, FEV1/FVC, PT, TT and APTT in observation group after treatment were significantly increased, and were significantly higher than the control group after treatment, PaCO2, D-D, Fib were significantly lower, and were lower than the control group after treatment, the differences were statistically significant (allP<0.05).Conclusions:AECOPD patients treated with low molecular heparin can help to improve the arterial blood gas, lung function and blood coagulation function.

  5. Changes and significance of coagulation function, hemodynamics and blood rheology in women with pregnancy induced hypertension

    Institute of Scientific and Technical Information of China (English)

    Bang-Zhi Zeng; Bo Zhang; Yu-Na Wang

    2016-01-01

    Objective:To observe the changes of coagulation function, hemodynamics and blood rheology in patients with pregnancy induced hypertension, and to explore its clinical significance. Methods: A total of 88 cases of women with pregnancy induced hypertension who were admitted in our hospital from July 2011 to February 2016 were selected as the research objects, at the same time, 90 normal pregnant women were selected as normal late pregnancy group. The coagulation parameters, hemodynamics, blood rheology indexes were detected in the two groups.Results:Before delivery, values of the PT and AT-Ⅲ in pregnancy induced hypertension group were significantly lower than those in the normal late pregnancy group, and the values of D-D and FIB were significantly higher than those in the normal late pregnancy group. After delivery, values of the PT and AT-Ⅲ in pregnancy induced hypertension group were significantly higher, and the FIB value was significantly lower, there were no significant differences between the two group. But the D-D value was still significantly higher than that in the normal late pregnancy group. The blood flow dynamics parameter in pregnancy induced hypertension group were significantly higher than that in the normal late pregnant group, the differences were statistically significant. The whole blood high and low shear viscosity, plasma viscosity, low shear reduction viscosity, hematocrit, erythrocyte deformation index, erythrocyte electrophoresis time and fibrinogen in pregnancy induced hypertension group were significantly higher than those in normal late pregnancy group.Conclusion:The blood indexes in patients with pregnancy induced hypertension showed a high coagulation state compared with the normal late pregnancy women. Timely detection of patients’ coagulation function, hemodynamics, and blood rheology indexes has important significance for the detection, auxiliary diagnosis and prevention of the disease.

  6. ARTEMISIA DRACUNCULUS, PUNICA GRANATUM AND BERBERIS VULGARIS INHIBITORY EFFECTS ON PLATELET ADHESION AND COAGULATION FACTORS IN RATS

    OpenAIRE

    Dr. Razieh Yazdanparast et al

    2012-01-01

    Excessive platelet activity is one of the most important factors responsible for the incidence of cardiovascular diseases and, also, play important role in coagulation cascade. In this study, the comparative effects of methanol extracts of three herbs on adhesion of the activated platelets to fibrinogen coated plates and clotting factors were investigated. Artemisia dracunculus, Punica granatum and Brberis vulgaris are used as blood anti-coagulatory plants in Iranian folk medicine. Platelets ...

  7. The Massive Bleeding after the Operation of Hip Joint Surgery with the Acquired Haemorrhagic Coagulation Factor XIII(13) Deficiency: Two Case Reports.

    Science.gov (United States)

    Kanda, Akio; Kaneko, Kazuo; Obayashi, Osamu; Mogami, Atsuhiko

    2013-01-01

    Two women, aged 81 and 61, became haemorrhagic after surgery. Their previous surgeries were uneventful with no unexpected bleeding observed. Blood tests prior to the current surgeries indicated normal values including those related to coagulation. There were no problems with the current surgeries prior to leaving the operating room. At 3 hours after the surgery, the 81-year-old patient had an outflow of the drain at 1290 grams and her blood pressure decreased. She had disseminated intravascular coagulation (DIC). The 61-year-old woman had repeated haemorrhages after her current surgery for a long time. Their abnormal haemorrhages were caused by a deficiency of coagulation factor XIII(13). The mechanism of haemorrhagic coagulation factor XIII(13) deficiency is not understood, and it is a rare disorder. The only diagnostic method to detect this disorder is to measure factor XIII(13) activity in the blood. In this paper, we used Arabic and Roman numerals at the same time to avoid confusion of coagulation factor XIII(13) with coagulation factor VIII(8) that causes hemophilia A. PMID:23533879

  8. The Massive Bleeding after the Operation of Hip Joint Surgery with the Acquired Haemorrhagic Coagulation Factor XIII(13 Deficiency: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Akio Kanda

    2013-01-01

    Full Text Available Two women, aged 81 and 61, became haemorrhagic after surgery. Their previous surgeries were uneventful with no unexpected bleeding observed. Blood tests prior to the current surgeries indicated normal values including those related to coagulation. There were no problems with the current surgeries prior to leaving the operating room. At 3 hours after the surgery, the 81-year-old patient had an outflow of the drain at 1290 grams and her blood pressure decreased. She had disseminated intravascular coagulation (DIC. The 61-year-old woman had repeated haemorrhages after her current surgery for a long time. Their abnormal haemorrhages were caused by a deficiency of coagulation factor XIII(13. The mechanism of haemorrhagic coagulation factor XIII(13 deficiency is not understood, and it is a rare disorder. The only diagnostic method to detect this disorder is to measure factor XIII(13 activity in the blood. In this paper, we used Arabic and Roman numerals at the same time to avoid confusion of coagulation factor XIII(13 with coagulation factor VIII(8 that causes hemophilia A.

  9. Prophylactic use of tranexamic acid combined with thrombelastogram guided coagulation management may reduce blood loss and allogeneic transfusion in pediatric hemispherectomy: case series.

    Science.gov (United States)

    Xiao, Wei; Fu, Wenya; Wang, Tianlong; Zhao, Lei

    2016-09-01

    Hemispherectomy is an established surgical procedure to treat medically refractory epilepsy caused by diffuse hemispheric diseases. The most common complication of hemispherectomy is intraoperative bleeding. Perioperative allogeneic blood transfusion increases mortality and morbidity in pediatric patients. Etiologies of massive blood loss during hemispherectomy include intraoperative diffuse vascular damage, antileptic drugs induced coagulation dysfunction, hyperfibrinolysis and dilutional coagulopathy. Great efforts should be made to minimize the need of blood transfusion. We present a series of three cases undergoing pediatric hemispherectomy, where a new algorithm was employed to manage coagulation. This new algorithm was mainly based on timely thrombelastogram analyses guided clotting factors supplement and continuous administration of tranexamic acid. In our cases, the amount of blood loss and subsequent allogeneic blood transfusion seemed to be less than literature reported. PMID:27555151

  10. Effects of plateletpheresis on blood coagulation parameters in healthy donors at National Blood Centre, Kuala Lumpur, Malaysia.

    Science.gov (United States)

    Siti Nadiah, A K; Nor Asiah, M; Nur Syimah, A T; Normi, M; Anza, E; Aini, A Nor; Mohd Zahari, T H; Shahnaz, M; Faraizah, A K; Faisal, M A

    2013-12-01

    Plateletpheresis is a method used to remove platelet from the body either from random volunteer donors, patient's family members or HLA matched donors. A cross sectional study was carried out on 59 plateletpheresis donors aged between 18 and 55 years at National Blood Center (NBC), Kuala Lumpur. We compared the blood parameters before and after plateletpheresis and we found that the platelet count, FVIII, fibrinogen and thrombophilia markers anti-thrombin (AT), protein C and protein S were significantly reduced (p<0.05) with prolonged PT and APTT. There were significant changes in blood coagulation parameters but it is within acceptable range.

  11. Factor VIII inhibitors in mild haemophilia A

    NARCIS (Netherlands)

    Bril, Wendy Simone

    2003-01-01

    The X-linked bleeding disorder haemophilia A is due to a deficiency or functional defect of coagulation factor VIII. The bleeding tendency can be corrected by administration of factor VIII concentrates. A serious complication of factor VIII replacement therapy is the development of anti-factor VIII

  12. Measurement of factor v activity in human plasma using a microplate coagulation assay.

    Science.gov (United States)

    Tilley, Derek; Levit, Irina; Samis, John A

    2012-09-09

    In response to injury, blood coagulation is activated and results in generation of the clotting protease, thrombin. Thrombin cleaves fibrinogen to fibrin which forms an insoluble clot that stops hemorrhage. Factor V (FV) in its activated form, FVa, is a critical cofactor for the protease FXa and accelerator of thrombin generation during fibrin clot formation as part of prothrombinase (1, 2). Manual FV assays have been described (3, 4), but they are time consuming and subjective. Automated FV assays have been reported (5-7), but the analyzer and reagents are expensive and generally provide only the clot time, not the rate and extent of fibrin formation. The microplate platform is preferred for measuring enzyme-catalyzed events because of convenience, time, cost, small volume, continuous monitoring, and high-throughput (8, 9). Microplate assays have been reported for clot lysis (10), platelet aggregation (11), and coagulation Factors (12), but not for FV activity in human plasma. The goal of the method was to develop a microplate assay that measures FV activity during fibrin formation in human plasma. This novel microplate method outlines a simple, inexpensive, and rapid assay of FV activity in human plasma. The assay utilizes a kinetic microplate reader to monitor the absorbance change at 405 nm during fibrin formation in human plasma (Figure 1) (13). The assay accurately measures the time, initial rate, and extent of fibrin clot formation. It requires only μl quantities of plasma, is complete in 6 min, has high-throughput, is sensitive to 24-80 pM FV, and measures the amount of unintentionally activated (1-stage activity) and thrombin-activated FV (2-stage activity) to obtain a complete assessment of its total functional activity (2-stage activity - 1-stage activity). Disseminated intravascular coagulation (DIC) is an acquired coagulopathy that most often develops from pre-existing infections (14). DIC is associated with a poor prognosis and increases mortality

  13. TO INVESTIGATE THE ACTION OF GINGER-JUICE ZINGIBER OFFICINALE ROSCOE (ZINGIBERACEAE ON BLOOD COAGULATION PROCESS.

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    S.S.Prasad

    2012-07-01

    Full Text Available Investigation of ginger-juice (zingiber officinale roscoe action on blood coagulation process in rat. Methods: (A Albino Wister rats (n=6-12 were administered G.J at two doses (2ml & 4 ml/rat, p.o as single administration and chronic treatment over period of 30 days. Following this assessment was done for possible effects on the blood coagulation. Parameters used during assessment were on the bleeding time, clotting time. prothrombin time, thrombin time, partial thromboplastin with kaolin (PTTk and platelet count. Results: Chronicadministration of G.J (2ml & 4ml/rat, p.o caused an increase in the bleeding time. There is no effect of gingerjuice treatment (2ml & 4ml/rat, p.o for 30 days on the clotting time, prothrombin time, thrombin time, partial thromboplastin time with kaolin (PTTk, and Platelet counts. Conclusion: Ginger administration increasedbleeding time on chronic administration G.J in two different doses.

  14. 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

    2016-10-01

    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. PMID:27322757

  15. [Evaluation of the severity course and prognosis of disseminated intravascular blood coagulation syndrome].

    Science.gov (United States)

    Kinakh, M V; Chaplyk, V V; Fedchyshyn, N R

    2009-01-01

    Activation of the peroxidal oxidation of lipids (POL) processes with its primary and secondary products levels raising constitutes a favourable sign, according to data of examination of 66 patients, suffering different phases of disseminated intravascular blood coagulation syndrome (DIBCS). The POL products contents reduction (areactive course) characterizes the process severity and constitutes an unfavourable prognostical sign. The areactive course rate is the highest in the patients, suffering DIBCS, phase III.

  16. Refreezing previously thawed fresh-frozen plasma. Stability of coagulation factors V and VIII:C.

    Science.gov (United States)

    Dzik, W H; Riibner, M A; Linehan, S K

    1989-09-01

    With the growth in autologous blood programs and the increased scrutiny of the indications for transfusion of fresh-frozen plasma (FFP), an increase has been seen in the number of occasions on which FFP was requested and thawed but then not transfused. The coagulation properties of FFP units that were refrozen and then rethawed were therefore studied. Fifty-eight units of plasma were studied, with each experimental unit of FFP paired with an identical control unit. Experimental units were frozen, stored at -65 degrees C, thawed, stored at 1 to 6 degrees C for various periods of time up to 24 hours, and then refrozen, stored at -65 degrees C, rethawed, and stored again in the refrigerator for up to 24 hours. Control units were frozen once at the time the experimental units were first frozen and thawed once at the time of the second thaw of the experimental units. Aliquots of plasma were sampled periodically and were later batch-tested for prothrombin time (PT), activated partial thromboplastin time (aPTT), and factor V and VIII:C activity. The results of coagulation testing of the twice-frozen plasmas were always within the normal range. There was a slight but statistically valid prolongation of the PT and aPTT and a decrease in the factor V and VIII:C levels for twice-frozen plasma compared with control plasma. The greatest decline occurred in the level of factor VIII:C. The measured deterioration in coagulation of twice-frozen FFP is unlikely to be of clinical importance. Refreezing FFP may eventually prove useful for rare donor, autologous, and massive transfusion programs.

  17. Quartz crystal microbalance-with dissipation monitoring (QCM-D) for real time measurements of blood coagulation density and immune complement activation on artificial surfaces.

    Science.gov (United States)

    Andersson, Marcus; Andersson, Jonas; Sellborn, Anders; Berglin, Mattias; Nilsson, Bo; Elwing, Hans

    2005-07-15

    A recently developed variant of quartz crystal microbalance (QCM) called QCM-with dissipation monitoring (QCM-D) allows simultaneous and simple measurements of changes in adsorbed mass as well as the viscoelastic property (D-factor) of deposited protein layers on the sensor surface. We have taken the QCM-D technology a step further and demonstrated its advantages in the study of protein assembly as a consequence of surface induced immune complement activation, or contact activated blood coagulation. In the present study we have continued our QCM-D investigations of surface assembly of fibrin clot formation and complement activation and incubated differently modified quartz sensor surfaces in blood plasma and sera. Polymer surfaces used were spin-coated polyethylene, poly(ethylene terephtalate), poly(methylmetacrylate) and poly(dimethylsiloxane). Also used were sputtered titanium and heparin grafted surfaces. In this investigation we found that we could describe the surface induced coagulation with four independent parameters: (1) Time of onset of coagulation, (2) fibrin deposition rate, (3) total frequency shift at stable plateau, and (4) fibrin clot density. The most important finding was that the blood plasma clot density can be assessed with the use of D determinations and that the clot density varied significantly with the chemical composition of the surface. However, the D-factor did not give any new analytical information about the possible complement activation mechanisms. Nevertheless, the QCM-D was found to be a reliable tool for the analysis of surface induced complement activation. We also compared the QCM-D technique with traditional enzyme immuno assay (EIA) measurements of soluble products from the surface activation of the complement and coagulation systems. We found that the results from EIA and QCM-D measurements corresponded well for the complement activation but not for the coagulation, probably due to the biological complexity of the coagulation

  18. Effects of long and short carboxylated or aminated multiwalled carbon nanotubes on blood coagulation.

    Directory of Open Access Journals (Sweden)

    Jie Meng

    Full Text Available In this work the effects of four different multiwalled carbon nanotubes (MWCNTs, including long carboxylated (L-COOH, short carboxylated (S-COOH, long aminated (L-NH(2 and short aminated (S-NH(2 ones, on the integrity of red blood cells, coagulation kinetics and activation of platelets were investigated with human whole blood. We found that the four MWCNTs induced different degrees of red blood cell damage as well as a mild level of platelet activation (10-25%. L-COOH and L-NH(2 induced a higher level of platelet activation than S-COOH and S-NH(2 respectively; meanwhile L-NH(2 caused marked reductions in platelet viability. The presence of the four MWCNTs led to earlier fibrin formation, L-NH(2 increased the clots hardness significantly, while L-COOH and S-NH(2 made the clots become softer. It was concluded that the four MWCNTs affected blood coagulation process and the clots mechanical properties; they also altered the integrity of the red blood cells and the viability of the platelets, as well as induced platelets activation. The effects of MWCNTs depended on the size and chemistry of the nanotubes and the type of cells they contacted.

  19. Development of a method for measuring blood coagulation using superparamagnetic iron oxide nanoparticles and an alternating magnetic field

    CERN Document Server

    Murase, Kenya

    2016-01-01

    We developed a method for measuring blood coagulation using superparamagnetic iron oxide nanoparticles (SPIONs) and an alternating magnetic field (AMF). The 3rd and 5th harmonic signals from SPIONs mixed with blood induced by AMF were detected using a gradiometer coil. Blood coagulation was induced artificially by adding CaCl2 solution to whole blood of sheep at various temperatures and hematocrits. We calculated the coagulation rate (k) and normalized signal intensity at infinite time (Sinf) by fitting the time course of the normalized 3rd harmonic signal to S(t)=(1-Sinf)exp(-kt)+Sinf. The k values increased significantly with increasing temperature and decreased significantly with increasing hematocrit. The Sinf values decreased significantly with increasing temperature and tended to increase with increasing hematocrit. Blood anticoagulation was induced by adding heparin to the whole blood sampled from mice. There were significant differences in both the 3rd and 5th harmonic signals between groups with and ...

  20. The role of structural information in the discovery of direct thrombin and factor Xa inhibitors.

    Science.gov (United States)

    Nar, Herbert

    2012-05-01

    The quest for novel medications to treat thromboembolic disorders such as venous thrombosis, pulmonary embolism and stroke received a boost when the 3D structures of two major players in the blood coagulation cascade were determined in 1989 and 1993. Structure-guided design of inhibitors of thrombin (factor IIa, fIIa) and factor Xa (fXa) eventually led to the discovery of potent, selective, efficacious, orally active and safe compounds that proved successful in clinical studies. In 2008, the direct thrombin inhibitor dabigatran etexilate developed by Boehringer Ingelheim became the first novel antithrombotic molecular entity to enter the market in 50 years. Additional compounds targeting factor Xa were subsequently granted marketing authorization or are in late-stage clinical studies. In this review, I use selected case studies to describe the discovery of novel fIIa and fXa inhibitors, with a particular emphasis on the pre-eminent role that structural information played in this process. PMID:22503439

  1. 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.

  2. Blood Coagulation Induced by Iranian Saw-Scaled Viper (Echis Carinatus Venom: Identification, Purification and Characterization of a Prothrombin Activator

    Directory of Open Access Journals (Sweden)

    Mahdi Babaie

    2013-11-01

    Full Text Available   Objective(s: Echis carinatus is one of the venomous snakes in Iran. The venom of Iranian Echis carinatus is a rich source of protein with various factors affecting the plasma protein and blood coagulation factor. Some of these proteins exhibit types of enzymatic activities. However, other items are proteins with no enzymatic activity.   Materials and Methods: In order to study the mechanism and effect of the venom on human plasma proteins, the present study has evaluated the effect of crude venom and all fractions. A procoagulant factor (prothrombin activator was isolated from the venom of the Iranian snake Echis carinatus with a combination of gel filtration (Sephadex G-75, ion-exchange chromatography (DEAE- Sepharose and reverse phase HPLC. Furthermore, proteolytic activity of the crude venom and all fractions on blood coagulation factors such as prothrombin time (PT was studied. Results: In the present study, the PT test was reduced from 13.4 s to 8.6 s when human plasma was treated with crude venom (concentraion of venom was 1 mg/ml. The purified procoagulant factor revealed a single protein band in SDS polyacrylamide electrophoresis under reducing conditions and its molecular weight was estimated at about 65 kDa. A single-band protein showed fragment patterns similar to those generated by the group A prothrombin activators, which convert prothrombin into meizothrombin independent of the prothrombinase complex. Conclusion: This study showed that the fraction which separated from Iranian snake Echis carinatus venom can be a prothrombin activators. It can be concluded that this fraction is a procoagulant factor.

  3. Treatment of Epilepsy with Bipolar Electro-coagulation: An Analysis of Cortical Blood Flow and Histological Change in Temporal Lobe

    Institute of Scientific and Technical Information of China (English)

    Zhi-Qiang Cui; Guo-Ming Luan; Jian Zhou; Feng Zhai; Yu-Guang Guan; Min Bao

    2015-01-01

    Background:Bipolar electro-coagulation has a reported efficacy in treating epilepsy involving functional cortex by pure electro-coagulation or combination with resection.However,the mechanisms of bipolar electro-coagulation are not completely known.We studied the acute cortical blood flow and histological changes after bipolar electro-coagulation in 24 patients with intractable temporal lobe epilepsy.Methods:Twenty-four patients were consecutively enrolled,and divided into three groups according to the date of admission.The regional cortical blood flow (rCBF),electrocorticography,the depth of cortex damage,and acute histological changes (H and E staining,neuronal staining and neurofilament (NF) staining) were analyzed before and after the operation.The t-test analysis was used to compare the rCBF before and after the operation.Results:The rCBF after coagulation was significantly reduced (P < 0.05).The spikes were significantly reduced after electro-coagulation.For the temporal cortex,the depth of cortical damage with output power of 2-9 W after electro-coagulation was 0.34 ± 0.03,0.48 ± 0.06,0.69 ± 0.06,0.84 ± 0.09,0.98 ± 0.08,1.10 ± 0.1 l,1.11 ± 0.09,and 1.22 ± 0.11 mm,respectively.Coagulation with output power of 4-5 W completely damaged the neurons and NF protein in the molecular layer,external granular layer,and external pyramidal layer.Conclusions:The electro-coagulation not only destroyed the neurons and NF protein,but also reduced the rCBF.We concluded that the injuries caused by electro-coagulation would prevent horizontal synchronization and spread of epileptic discharges,and partially destroy the epileptic focus.

  4. Effects of Replenishing Qi, Promoting Blood Circulation and Resolving Phlegm on Vascular Endothelial Function and Blood Coagulation System in Senile Patients with Hyperlipemia

    Institute of Scientific and Technical Information of China (English)

    Yang Huimin; Han Libei; Sheng Tong; He Qiong; Liang Jinpu

    2006-01-01

    Objective: To observe the curative effect of the method of replenishing qi, promoting blood circulation and resolving phlegm on senile hyperlipemia and its effects on vascular endothelial function and blood coagulation system. Method: 96 patients with senile hyperlipemia were randomly divided into a treatment group and a of blood lipid, vascular endothelial function, blood coagulation system and safety. Results: After treatment,the treatment group was obviously superior to the control group (P<0.05) in reducing plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) as well as in the ratio of thromboxane B2 (TXB2) to 6-keto-prostaglandin F1α (6-keto-PGF1α), D-dimer (D-D) and fibrinogen (FIB). Conclusion: Danshen Jueming Granules have the effect of regulating metabolism of blood lipid, and improving vascular endothelial function and blood coagulation system in senile patients with hyperlipemia.

  5. The Changes of Blood Coagulation in Surgical Patients with Lung Cancer

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    Xiangning FU

    2010-02-01

    Full Text Available Background and objective Patients with malignant tumor are at high risk of thrombophilia, which contributes to thromboembolism. Surgical treatment is one of the critical risk factors. In this study, changes and clinical significances of blood coagulation of lung cancer patients pre- and post operation were investigated. Methods A prospective, controlled study were carried out in 74 lung disease patients, who were divided into lung cancer group and benign lung disease group. In each group, pre-and postoperative changes in prothrombin time (PT, activated partial thromboplastin time (APTT, platelet count (PLT, D-dimer (D-D and fibrinogen (Fib and clinical performances were observed and compared in intra- and intergroups. Results The concentration of Fib both in lung cancer group and its subgroup (adenocarcinoma of lung increased, preoperative differences between benign lung disease group and subgroup (squamous cell carcinoma of lung was significant (P < 0.05. PT(postoperative 1st to7th day in lung cancer group prolonged, APTT (postoperative 3rd to7th day reduced, Fib (postoperative 3rd to7th day and D-D (postoperative 1st to 7th day increased, PLT reduced on the 1st, 3rd day but then increased on the 5th, 7th day after operation, the difference between pre- and post-operation was significant (P < 0.05. D-D and PT in lung cancer group on the 7th day was longer than in benign lung disease group (P < 0.05. One pulmonary thromboembolism (PTE case in lung cancer group occurred, while in benign lung disease group none venous thromboembolism (VTE appeared. Conclusion Patients with lung cancer are in high hypercoagulable state, and prone to VTE. It is necessary to take some interventions to avoid VTE.

  6. Erythrocyte-derived microparticles supporting activated protein C-mediated regulation of blood coagulation.

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    Ruzica Livaja Koshiar

    Full Text Available Elevated levels of erythrocyte-derived microparticles are present in the circulation in medical conditions affecting the red blood cells. Erythrocyte-derived microparticles expose phosphatidylserine thus providing a suitable surface for procoagulant reactions leading to thrombin formation via the tenase and prothrombinase complexes. Patients with elevated levels of circulating erythrocyte-derived microparticles have increased thrombin generation in vivo. The aim of the present study was to investigate whether erythrocyte-derived microparticles are able to support the anticoagulant reactions of the protein C system. Erythrocyte-derived microparticles were isolated using ultracentrifugation after incubation of freshly prepared erythrocytes with the ionophore A23187 or from outdated erythrocyte concentrates, the different microparticles preparations yielding similar results. According to flow cytometry analysis, the microparticles exposed phoshatidylserine and bound lactadherin, annexin V, and protein S, which is a cofactor to activated protein C. The microparticles were able to assemble the tenase and prothrombinase complexes and to stimulate the formation of thrombin in plasma-based thrombin generation assay both in presence and absence of added tissue factor. The addition of activated protein C in the thrombin generation assay inhibited thrombin generation in a dose-dependent fashion. The anticoagulant effect of activated protein C in the thrombin generation assay was inhibited by a monoclonal antibody that prevents binding of protein S to microparticles and also attenuated by anti-TFPI antibodies. In the presence of erythrocyte-derived microparticles, activated protein C inhibited tenase and prothrombinase by degrading the cofactors FVIIIa and FVa, respectively. Protein S stimulated the Arg306-cleavage in FVa, whereas efficient inhibition of FVIIIa depended on the synergistic cofactor activity of protein S and FV. In summary, the erythrocyte

  7. Expression patterns and action analysis of genes associated with blood coagulation responses during rat liver regeneration

    Institute of Scientific and Technical Information of China (English)

    Li-Feng Zhao; Wei-Min Zhang; Cun-Shuan Xu

    2006-01-01

    AIM:To study the blood coagulation response after partial hepatectomy (PH) at transcriptional level.METHODS:After PH of rats, the associated genes with blood coagulation were obtained through reference to the databases, and the gene expression changes in rat regenerating liver were analyzed by the Rat Genome 230 2.0 array.RESULTS: It was found that 107 genes were associated with liver regeneration. The initially and totally expressing gene numbers occurring in initiation phase of liver regeneration (0.5-4 h after PH), G0/G1 transition (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and structure-function reconstruction (66-168 h after PH) were 44, 11, 58, 7 and 44, 33,100, 71 respectively, showing that the associated genes were mainly triggered in the forepart and prophase, and worked at different phases. According to their expression similarity, these genes were classified into 5 groups:only up-, predominantly up-, only down-, predominantly down-, up- and down-regulation, involving 44, 8, 36,13 and 6 genes, respectively, and the total times of their up- and down-regulation expression were 342 and 253, respectively, demonstrating that the number of the up-regulated genes was more than that of the downregulated genes. Their time relevance was classified into 15 groups, showing that the cellular physiological and biochemical activities were staggered during liver regeneration. According to gene expression patterns,they were classified into 29 types, suggesting that their protein activities were diverse and complex during liver regeneration.CONCLUSION: The blood coagulation response is enhanced mainly in the forepart, prophase and anaphase of liver regeneration, in which the response in the forepart, prophase of liver regeneration can prevent the bleeding caused by partial hepatectomy, whereas that in the anaphase contributes to the structure-function reorganization of regenerating liver. In the process,107 genes associated with liver

  8. Tissue factor pathway inhibitor relates to fibrin degradation in patients with acute deep venous thrombosis

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Bladbjerg, Else-Marie; Gram, Jørgen;

    2008-01-01

    Reduced concentration of tissue factor pathway inhibitor is a risk factor for development of deep venous thrombosis, whereas elevated concentrations of tissue factor pathway inhibitor are observed in patients with acute myocardial infarction and disseminated intravascular coagulation. Presently, we...... studied the association between inflammation, endothelial cell perturbation, fibrin degradation and the concentration of tissue factor pathway inhibitor in patients suspected for acute deep venous thrombosis. We determined the tissue factor pathway inhibitor -33T/C polymorphism, free and total tissue...... factor pathway inhibitor, C-reactive protein, von Willebrand factor and D-Dimer in 160 consecutive patients admitted to hospital with a tentative diagnosis of acute deep venous thrombosis. Deep venous thrombosis was identified in 57 patients (18 distal and 39 proximal). The distribution of the tissue...

  9. Advances on Mechanisms of Coagulation with Non-small Cell Lung Cancer

    OpenAIRE

    Yanhua LI; Suju WEI

    2013-01-01

    Recently, researchers have been increasingly finding coagulation disorders are commonly the first sign of malignancy. It has now been established that cancer development leads to an increased risk of thrombosis, and conversely, excessive activation of blood coagulation profoundly influences cancer progression. In patients with lung cancer, a sustained stimulation of blood coagulation takes place. Cancer cells trigger coagulation through expression of tissue factor, and affect coagulation thro...

  10. Inhibition of coagulation factors by recombinant barley serpin BSZx

    DEFF Research Database (Denmark)

    Dahl, Søren Weis; Rasmussen, S.K.; Petersen, L..C.;

    1996-01-01

    Barley serpin BSZx is a potent inhibitor of trypsin and chymotrypsin at overlapping reactive sites (Dahl, S.W., Rasmussen, S.K. and Hejgaard, J. (1996) J. Biol, Chem., in press), We have now investigated the interactions of BSZx with a range of serine proteinases from human plasma, pancreas...... as substrate, Complexes of these proteinase with BSZx resisted boiling in SDS, and amino acid sequencing showed that cleavage in the reactive center loop only occurred after P-1 Arg. Activated protein C and leukocyte elastase were slowly inhibited by BSZx (k(ass) = 1-2 x 10(2) M(-1) s(-1)) whereas factor XIIa...... and leukocytes, a fungal trypsin and three subtilisins, Thrombin, plasma kallikrein, factor VIIa/tissue factor and factor Xa were inhibited by BSZx at heparin independent association rates (k(ass)) of 4.5 x 10(3)-1.3 x 10(5) M(-1) s(-1) at 22 degrees C. Only factor Xa turned a significant fraction of BSZx over...

  11. Coagulation inhibitors and activated protein C resistance in recurrent pregnancy losses in Indian women

    Directory of Open Access Journals (Sweden)

    P Lalita Jyotsna

    2011-01-01

    Full Text Available Background: Thrombophilias, both acquired and inherited, have been investigated in the etiopathogenesis of unexplained recurrent pregnancy loss. Aim: To study coagulation inhibitors and activated protein C resistance (APCR in recurrent pregnancy losses (RPL occurring in second and third trimesters. Materials and Methods: A total of 30 pregnant women (group A with two or more recurrent unexplained fetal loses were evaluated for APCR, protein C deficiency, protein S deficiency, antithrombin deficiency, and antiphospholipid antibodies (APLA. Thirty age-matched controls were taken (group B comprising of pregnant women with at least one live issue. Statistical Analysis: Comparisons between two group frequencies and group means were made using Chi square test and Student′s t test, respectively. Results: Protein C and protein S levels were reduced in group A compared with group B and the difference was statistically significant (P=0.005 and P=0.032, respectively. The mean value of antithrombin was slightly reduced in group A compared with group B. APCR was observed in 16.6% cases and 3.3% controls. However, the difference was not statistically significant. APLA was observed in 20% cases and none of the controls. Of these, lupus anticoagulant was positive in 16.6% cases and anticardiolipin antibodies in 10% cases. Combined defects were seen in seven patients. Conclusion: There is a significant risk of RPL in pregnant women with thrombophilias. Therefore, screening for thrombophilias may be justified in pregnant women with unexplained recurrent fetal wastage, especially in second and third trimester.

  12. Disseminated intravascular coagulation does not play a major role in the pathogenesis of classical swine fever.

    Science.gov (United States)

    Blome, Sandra; Meindl-Böhmer, Alexandra; Nowak, Götz; Moennig, Volker

    2013-03-23

    Classical swine fever (CSF) is a multi-systemic disease that can be accompanied by severe haemorrhagic lesions. The underlying pathogenetic mechanisms are still far from being understood, though disseminated intravascular coagulation (DIC) was discussed as a major factor. In the presented study, the direct thrombin inhibitor hirudin was used in an attempt to elucidate the role of the coagulation system in the pathogenesis of CSF-induced haemorrhagic lesions. Two groups of piglets (n=5) were infected with highly virulent CSF virus (CSFV) strain CSF0634. One group underwent daily treatment with hirudin, the other served as untreated challenge infection control. Assessment of clinical signs using a clinical score system, coagulation tests, and blood counts were performed daily. Both groups developed acute-lethal CSF with haemorrhagic lesions. Although changes in the coagulation system were seen in the late stages of CSFV infection, our results strongly suggest that DIC does not present the crucial event in the pathogenesis of haemorrhagic lesions.

  13. Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.

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    Massimo Cugno

    Full Text Available Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011 and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively (P<0.0001. Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.

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

    International Nuclear Information System (INIS)

    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 Arg152-Ile153. 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 Arg152 → 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 Mr∼40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX

  15. Interpreting coagulation assays.

    Science.gov (United States)

    Green, David

    2010-09-01

    The interpretation of coagulation assays requires knowledge of the principal clotting pathways. The activated partial thromboplastin time is sensitive to all hemostatic factors except FVII, whereas the prothrombin time reflects levels of prothrombin and FV, FVII, and FX. Using the two tests in concert is helpful in identifying hemophilia, the coagulopathy of liver disease, and disseminated intravascular coagulation. In addition, the activated partial thromboplastin time and prothrombin time are used for monitoring anticoagulant therapy with heparin and warfarin, respectively. Measurement of D-dimer is informative in patients suspected of having thrombotic disorders and determining the risk of thrombosis recurrence. Mixing tests distinguish clotting factor deficiencies from circulating anticoagulants such as heparin, the lupus anticoagulant, and antibodies directed against specific clotting factors. The modified Bethesda assay detects and provides an indication of the strength of FVIII inhibitors. However, interpreting the results of coagulation assays is not always straightforward, and expert consultation is occasionally required to resolve difficult clinical situations. PMID:20855988

  16. 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.

  17. Analysis of blood coagulation in mice: pre-analytical conditions and evaluation of a home-made assay for thrombin-antithrombin complexes

    Directory of Open Access Journals (Sweden)

    Meijers Joost CM

    2005-08-01

    Full Text Available Abstract Background The use of mouse models for the study of thrombotic disorders has gained increasing importance. Methods for measurement of coagulation activation in mice are, however, scarce. The primary aim of this study was to develop a specific mouse thrombin-antithrombin (TAT ELISA for measurement of coagulation activation and to compare it with two commercially available assays for human TAT complexes. In addition, we aimed to improve methods for mouse plasma anticoagulation and preparation. Methods and results First, for the measurement of TAT-complexes in plasma a mouse specific TAT-ELISA was developed using rabbit polyclonal antibodies raised against mouse thrombin and rat antithrombin, respectively. This ELISA detected an increase in TAT levels in a mouse model of endotoxemia. Two commercial human TAT ELISAs appeared to be less specific for mouse thrombin-rat antithrombin complexes. Second, to prevent clotting of mouse blood sodium citrate was either mixed with blood during collection in a syringe or was injected intravenously immediately prior to blood collection. Intravenous sodium citrate completely inhibited blood coagulation resulting in plasma with consistently low TAT levels. Sodium citrate mixed with blood during collection resulted in increased TAT levels in 4 out of 16 plasma samples. Third, heparinase was added to plasma samples after in vivo injection of different heparin doses to test its neutralizing effect. Heparinase neutralized up to a 20 U of heparin/mouse and resulted in accurate APTT and factor VIII determinations. Conclusion These procedures and reagents for plasma preparation and coagulation testing will improve studies on thrombotic disorders in mice.

  18. Duvernoy's gland secretion of Philodryas patagoniensis from the northeast of Argentina: its effects on blood coagulation.

    Science.gov (United States)

    Peichoto, M E; Leiva, L C; Guaimás Moya, L E; Rey, L; Acosta, O

    2005-03-15

    Duvernoy's gland secretion of Philodryas patagoniensis exhibits high hemorrhagic activity, containing enzymes that are able to degrade the vascular wall. In this work we aim to determine if the secretion can also affect the hemostatic system by causing changes in blood coagulation. Procoagulant and coagulant activities were evaluated on plasma and fibrinogen, respectively. The delay in the thrombin clotting time of fibrinogen previously incubated with the secretion was also determined. Specific hydrolysis of fibrinogen and fibrin incubated with the secretion at different time intervals was shown by electrophoresis on polyacrylamide gel. To determine the structural characteristics of the enzymes degrading fibrinogen and fibrin, secretion were incubated in the presence of 45 mM Na(2)EDTA, 40 mM Benzamidine, and/or 2 mM PMSF before the incubation with fibrinogen or fibrin, respectively. The effect in vivo was investigated in adult male rats injected with different dose of secretion, aliquots of blood were withdrawn at different time intervals, and the fibrinogen concentration was determined. Duvernoy's gland secretion of P. patagoniensis did not clot plasma or fibrinogen. It exhibited a potent fibrinogenolytic activity degrading the Aalpha-chain faster than the Bbeta-chain, whereas gamma-chain was resistant. This latter corresponded with a strong delay in the thrombin clotting time of fibrinogen (4 mg/ml) pre-incubated with the secretion, being 9.53 microg the amount of protein from Duvernoy's gland secretion that increased the thrombin clotting time from 20 to 60 s. In vivo, the loss of rat plasma fibrinogen was proportional to the amount of secretion injected. The secretion also hydrolyzed fibrin degrading the alpha-monomer. Inhibition studies with Na(2)EDTA, Benzamidine, and/or PMSF showed that metalloproteinases and serinoproteinases are the main enzymes responsible for the hydrolyzing activity on fibrinogen and fibrin. All these results demonstrate that Duvernoy

  19. 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)

  20. 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.

  1. Enhancement of pig embryonic implants in factor VIII KO mice: a novel role for the coagulation cascade in organ size control.

    Directory of Open Access Journals (Sweden)

    Anna Aronovich

    Full Text Available Very little is known about the mechanisms that contribute to organ size differences between species. In the present study, we used a mouse model of embryonic pig tissue implantation to define the role of host Factor VIII in controlling the final size attained by the implant. We show here that pig embryonic spleen, pancreas, and liver all grow to an increased size in mice that are deficient in the Factor VIII clotting cascade. Similar results were obtained using the transplantation model after treatment with the low molecular weight heparin derivative Clexane which markedly enhanced transplant size. Likewise, enhanced size was found upon treatment with the direct thrombin inhibitor Dabigatran, suggesting that organ size regulation might be mediated by thrombin, downstream of Factor VIII. Considering that thrombin was shown to mediate various functions unrelated to blood clotting, either directly by cleavage of protease-activated receptors (PARs or indirectly by cleaving osteopontin (OPN on stroma cells, the role of PAR1 and PAR4 antagonists as well as treatment with cleaved form of OPN (tcOPN were tested. While the former was not found to have an impact on overgrowth of embryonic pig spleen implants, marked reduction of size was noted upon treatment with the (tcOPN. Collectively, our surprising set of observations suggests that factors of the coagulation cascade have a novel role in organ size control.

  2. Effects of whole-body vibration training on fibrinolytic and coagulative factors in healthy young men

    Directory of Open Access Journals (Sweden)

    Farshad Ghazalian

    2014-01-01

    Full Text Available Background: The aim was to evaluate effects of 5-week whole body vibration (WBV training with different amplitudes and progressive frequencies on fibrinolytic/coagulative factors. Materials and Methods: 25 subjects were divided randomly in high or low-amplitude vibration, and control groups. Training consisted of 5-week WBV with amplitudes 4 or 2 mm. Plasma samples were analyzed before and after training. Statistical analysis was done using one-way analysis of variance and Wilcoxon signed ranked test. P <0.05 was considered significant. Results: High-amplitude vibration caused an increase in tissue plasminogen activator (tPA (P = 0.028 (pretest: 1744.61 ± 707.95; posttest: 2313.63 ± 997.19 pg/ml, and decrease in plasminogen activator inhibitor-1 (PAI-1 (P = 0.033 (pretest: 97.94 ± 34.37; posttest: 85.12 ± 36.92 ng/ml. Fibrinogen and plasminogen were not changed significantly. Low-amplitude vibration caused an increase in tPA (P = 0.006 (pretest: 2208.18 ± 1280.37; posttest: 3492.72 ± 3549.22 pg/ml. PAI-1, fibrinogen and plasminogen were not changed significantly. There were no significant differences between groups. Conclusion: Amplitude of vibrations in WBV training may affect fibrinolytic factors.

  3. Coagulation factor V mediates inhibition of tissue factor signaling by activated protein C in mice.

    Science.gov (United States)

    Liang, Hai Po H; Kerschen, Edward J; Basu, Sreemanti; Hernandez, Irene; Zogg, Mark; Jia, Shuang; Hessner, Martin J; Toso, Raffaella; Rezaie, Alireza R; Fernández, José A; Camire, Rodney M; Ruf, Wolfram; Griffin, John H; Weiler, Hartmut

    2015-11-19

    The key effector molecule of the natural protein C pathway, activated protein C (aPC), exerts pleiotropic effects on coagulation, fibrinolysis, and inflammation. Coagulation-independent cell signaling by aPC appears to be the predominant mechanism underlying its highly reproducible therapeutic efficacy in most animal models of injury and infection. In this study, using a mouse model of Staphylococcus aureus sepsis, we demonstrate marked disease stage-specific effects of the anticoagulant and cell signaling functions of aPC. aPC resistance of factor (f)V due to the R506Q Leiden mutation protected against detrimental anticoagulant effects of aPC therapy but also abrogated the anti-inflammatory and mortality-reducing effects of the signaling-selective 5A-aPC variant that has minimal anticoagulant function. We found that procofactor V (cleaved by aPC at R506) and protein S were necessary cofactors for the aPC-mediated inhibition of inflammatory tissue-factor signaling. The anti-inflammatory cofactor function of fV involved the same structural features that govern its cofactor function for the anticoagulant effects of aPC, yet its anti-inflammatory activities did not involve proteolysis of activated coagulation factors Va and VIIIa. These findings reveal a novel biological function and mechanism of the protein C pathway in which protein S and the aPC-cleaved form of fV are cofactors for anti-inflammatory cell signaling by aPC in the context of endotoxemia and infection.

  4. Structural and functional characterization of protein complexes in the blood coagulation cascade

    DEFF Research Database (Denmark)

    Madsen, Jesper Jonasson

    In this dissertation, components of coagulation factor (F)X-activating (tenase; fXase) complexes are studied using computational biophysics and the molecular dynamics (MD) method. The main focus is on structure-function relationships of the two central tenase complexes with respect to activation...... processes, complex formation, and platelet membrane association. Both the intrinsic and the extrinsic tenase complex consists of a trypsin-like serine protease and auxiliary domains complexed with the appropriate cofactor; FIXa with FVIIIa and FVIIa with tissue factor (TF), respectively. Topics covered...... are explained. Furthermore, the inter-domain linker connecting the two epidermal growth factor-like domains of FVIIa will be discussed with respect to consequences for its ability to form a productive complex with tissue factor. Finally, membrane binding of FVIIIa as mediated by the tandem C2-like domains...

  5. Removal of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) from water by coagulation: mechanisms and influencing factors.

    Science.gov (United States)

    Bao, Yueping; Niu, Junfeng; Xu, Zesheng; Gao, Ding; Shi, Jianghong; Sun, Xiaomin; Huang, Qingguo

    2014-11-15

    In this study, alum (Al2(SO4)3⋅18H2O), ferric chloride (FeCl3⋅6H2O) and polyaluminium chloride (PACl) were used to remove perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) from water. The influencing factors, including pH and natural organic matter (NOM), were investigated. A positive correlation was found between the size of the flocs and the removal efficiency of PFOX (X=S and A). The removal ratios of PFOS and PFOA were 32% and ∼12%, respectively, when 50 mg/L of FeCl3⋅6H2O was added as the coagulant at the initial pH. Coagulation achieved high removal ratios for PFOX under acidic conditions (∼47.6% and 94.7% for PFOA and PFOS at pH 4, respectively). In addition, increasing NOM concentrations decreased the removal rates of PFOX because of the existence of competitive adsorption between NOM molecules and PFOX on the surface of the coagulants and flocs. The combination of adsorption by powdered activated carbon (PAC) and coagulation increased the removal ratios up to >90% for PFOX at the initial concentration of 1mg/L, implying that the adsorption enhanced coagulation. Meantime, the experiments with natural water showed that coagulation is a feasible method to remove PFOS and PFOA from surface water.

  6. Removal of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) from water by coagulation: mechanisms and influencing factors.

    Science.gov (United States)

    Bao, Yueping; Niu, Junfeng; Xu, Zesheng; Gao, Ding; Shi, Jianghong; Sun, Xiaomin; Huang, Qingguo

    2014-11-15

    In this study, alum (Al2(SO4)3⋅18H2O), ferric chloride (FeCl3⋅6H2O) and polyaluminium chloride (PACl) were used to remove perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) from water. The influencing factors, including pH and natural organic matter (NOM), were investigated. A positive correlation was found between the size of the flocs and the removal efficiency of PFOX (X=S and A). The removal ratios of PFOS and PFOA were 32% and ∼12%, respectively, when 50 mg/L of FeCl3⋅6H2O was added as the coagulant at the initial pH. Coagulation achieved high removal ratios for PFOX under acidic conditions (∼47.6% and 94.7% for PFOA and PFOS at pH 4, respectively). In addition, increasing NOM concentrations decreased the removal rates of PFOX because of the existence of competitive adsorption between NOM molecules and PFOX on the surface of the coagulants and flocs. The combination of adsorption by powdered activated carbon (PAC) and coagulation increased the removal ratios up to >90% for PFOX at the initial concentration of 1mg/L, implying that the adsorption enhanced coagulation. Meantime, the experiments with natural water showed that coagulation is a feasible method to remove PFOS and PFOA from surface water. PMID:25168583

  7. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III

    Science.gov (United States)

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M.; Drouet, Christian; Braley, Hal; Nolte, Marc W.; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas

    2015-01-01

    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. PMID:26193639

  8. Revisiting the mechanism of coagulation factor XIII activation and regulation from a structure/functional perspective.

    Science.gov (United States)

    Gupta, Sneha; Biswas, Arijit; Akhter, Mohammad Suhail; Krettler, Christoph; Reinhart, Christoph; Dodt, Johannes; Reuter, Andreas; Philippou, Helen; Ivaskevicius, Vytautas; Oldenburg, Johannes

    2016-01-01

    The activation and regulation of coagulation Factor XIII (FXIII) protein has been the subject of active research for the past three decades. Although discrete evidence exists on various aspects of FXIII activation and regulation a combinatorial structure/functional view in this regard is lacking. In this study, we present results of a structure/function study of the functional chain of events for FXIII. Our study shows how subtle chronological submolecular changes within calcium binding sites can bring about the detailed transformation of the zymogenic FXIII to its activated form especially in the context of FXIIIA and FXIIIB subunit interactions. We demonstrate what aspects of FXIII are important for the stabilization (first calcium binding site) of its zymogenic form and the possible modes of deactivation (thrombin mediated secondary cleavage) of the activated form. Our study for the first time provides a structural outlook of the FXIIIA2B2 heterotetramer assembly, its association and dissociation. The FXIIIB subunits regulatory role in the overall process has also been elaborated upon. In summary, this study provides detailed structural insight into the mechanisms of FXIII activation and regulation that can be used as a template for the development of future highly specific therapeutic inhibitors targeting FXIII in pathological conditions like thrombosis. PMID:27453290

  9. Increased mortality in systemic inflammatory response syndrome patients with high levels of coagulation factor VIIa

    NARCIS (Netherlands)

    Hyseni, A.; Kemperman, H.; De Lange, D. W.; de Groot, P. G.; Linssen, M.; Kesecioglu, J.; Lisman, T.; Roest, M.

    2013-01-01

    BackgroundThe tissue factor (TF)- Factor VIIa (FVIIa) complex has a pivotal role in inflammatory and coagulation responses in patients with systemic inflammatory response syndrome (SIRS) and sepsis. Because zymogen FVII (FVII) and FVIIa compete for binding to TF, their plasma levels determine if a c

  10. Expression of Functional Human Coagulation Factor XIII A-domain in Plant Cell Suspensions and Whole Plants

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Johnway; Hooker, Brian S.; Anderson, Daniel B.

    2004-09-01

    Coagulation factor XIII, a zymogen present in blood as a tetramer (A2B2) of A- and B-domains, is one of the components of many ''wound sealants'' which are proposed for use or currently in use as effective hemostatic agents, sealants and tissue adhesives in surgery. After activation by ?-thrombin cleavage, coagulation factor XIII A-domain, a transglutaminase, is formed and catalyzes the covalent crosslinking of the ?- and ?-chains of linear fibrin to form homopolymers, which can quickly stop bleeding. We have successfully expressed the A-domain of factor XIII in both plant cell cultures and whole plants. Transgenic plant cell culture allows a rapid method for testing production feasibility while expression in whole plants demonstrates an economic production system for recombinant human plasma-based proteins. The expressed factor XIII A-domain had a similar size as that of human plasma-derived factor XIII. Crude plant extract containing recombinant factor XIII A-domain showed transglutaminase activity with monodansylcadaverine and casein as substrates and crosslinking activity in the presence of linear fibrin. The expression of factor XIII A-domain was not affected by plant leaf position.

  11. Preparation, blood coagulation and cell compatibility evaluation of chitosan-graft-polylactide copolymers.

    Science.gov (United States)

    Wang, Qi; Liu, Pei; Liu, Peifeng; Gong, Tao; Li, Suming; Duan, Yourong; Zhang, Zhirong

    2014-02-01

    Biodegradable chitosan-graft-polylactide (PLA-CS) copolymers were prepared by the grafting of a poly(L-lactide) (PLLA) or poly(D-lactide) (PDLA) precursor to the backbone of chitosan using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC ⋅ HCl) and N-hydroxysuccinimide (NHS) as a coupling agent. The blood and cell compatibility of the graft copolymers were investigated in comparison to PLLA and PDLA homopolymers. The coagulation properties of PLA-CS were evaluated by hemolysis, plasma recalcification, dynamic blood clotting and protein absorption assays. PLA-CS copolymers present similar hemolysis ratio and plasma recalcification time as PLA, but slower dynamic blood clotting and lower protein absorption. The cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), agar diffusion and lactate dehydrogenase (LDH) experiments. All the samples presented no effect on the viability to cells. Inflammatory cytokine analysis using sandwich ELISAs revealed that PLA-CS would not stimulate inflammatory activity. PMID:24448591

  12. Preparation, blood coagulation and cell compatibility evaluation of chitosan-graft-polylactide copolymers

    International Nuclear Information System (INIS)

    Biodegradable chitosan-graft-polylactide (PLA–CS) copolymers were prepared by the grafting of a poly(L-lactide) (PLLA) or poly(D-lactide) (PDLA) precursor to the backbone of chitosan using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC ⋅ HCl) and N-hydroxysuccinimide (NHS) as a coupling agent. The blood and cell compatibility of the graft copolymers were investigated in comparison to PLLA and PDLA homopolymers. The coagulation properties of PLA–CS were evaluated by hemolysis, plasma recalcification, dynamic blood clotting and protein absorption assays. PLA–CS copolymers present similar hemolysis ratio and plasma recalcification time as PLA, but slower dynamic blood clotting and lower protein absorption. The cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), agar diffusion and lactate dehydrogenase (LDH) experiments. All the samples presented no effect on the viability to cells. Inflammatory cytokine analysis using sandwich ELISAs revealed that PLA–CS would not stimulate inflammatory activity. (paper)

  13. Monitoring time course of human whole blood coagulation using a microfluidic dielectric sensor with a 3D capacitive structure.

    Science.gov (United States)

    Maji, Debnath; Suster, Michael A; Stavrou, Evi; Gurkan, Umut A; Mohseni, Pedram

    2015-08-01

    This paper reports on the design, fabrication, and testing of a microfluidic sensor for dielectric spectroscopy (DS) of human whole blood during coagulation. The sensor employs a three-dimensional (3D), parallel-plate, capacitive sensing structure with a floating electrode integrated into a microfluidic channel. Using an impedance analyzer and after a 5-point calibration, the sensor is shown to measure the real part of complex relative dielectric permittivity of human whole blood in a frequency range of 10kHz to 100MHz. The temporal variation of dielectric permittivity at 1MHz for human whole blood from three different healthy donors shows a peak in permittivity at ~ 4 to 5 minutes, which also corresponds to the onset of CaCl2-initiated coagulation of the blood sample verified visually. PMID:26737635

  14. Extraction of mRNA from coagulated horse blood and analysis of inflammation-related cytokine responses to coagulation

    DEFF Research Database (Denmark)

    Bovbjerg, Kirsten Katrine Lindegaard; Heegaard, Peter M. H.; Skovgaard, Kerstin

    2010-01-01

    available. Here, a protocol for RNA extraction from highly clotted blood was optimized and the regulation of a number of cytokine genes compared to stabilized blood was studied. Whole blood samples from 10 clinically healthy horses were incubated for 24 hours at 37°C and RNA was extracted from...

  15. MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked.

    Science.gov (United States)

    Dobó, József; Szakács, Dávid; Oroszlán, Gábor; Kortvely, Elod; Kiss, Bence; Boros, Eszter; Szász, Róbert; Závodszky, Péter; Gál, Péter; Pál, Gábor

    2016-01-01

    MASP-3 was discovered 15 years ago as the third mannan-binding lectin (MBL)-associated serine protease of the complement lectin pathway. Lacking any verified substrate its role remained ambiguous. MASP-3 was shown to compete with a key lectin pathway enzyme MASP-2 for MBL binding, and was therefore considered to be a negative complement regulator. Later, knock-out mice experiments suggested that MASP-1 and/or MASP-3 play important roles in complement pro-factor D (pro-FD) maturation. However, studies on a MASP-1/MASP-3-deficient human patient produced contradicting results. In normal resting blood unperturbed by ongoing coagulation or complement activation, factor D is present predominantly in its active form, suggesting that resting blood contains at least one pro-FD activating proteinase that is not a direct initiator of coagulation or complement activation. We have recently showed that all three MASPs can activate pro-FD in vitro. In resting blood, however, using our previously evolved MASP-1 and MASP-2 inhibitors we proved that neither MASP-1 nor MASP-2 activates pro-FD. Other plasma proteinases, particularly MASP-3, remained candidates for that function. For this study we evolved a specific MASP-3 inhibitor and unambiguously proved that activated MASP-3 is the exclusive pro-FD activator in resting blood, which demonstrates a fundamental link between the lectin and alternative pathways. PMID:27535802

  16. The change and significance of platelet parameters and blood coagulation function index in patients with hypertensive disorder complicating pregnancy

    Institute of Scientific and Technical Information of China (English)

    Yu-Xia Shi; Yi-Xin Yang; Qian Xu; Yanhua Zhu

    2015-01-01

    Objective:To explore the change and significance of platelet parameters and blood coagulation function index in patients with hypertensive disorder complicating pregnancy.Methods: Chose 89 patients with HDCP, they were set as HDCP group, chose another 60 cases health late pregnancy women and 42 cases non pregnant female, they were set as late pregnant group and non-pregnant control group, detected the platelet parameters: the average blood platelet count (PLT), platelet volume (MPV), platelet distribution width (PDW) and blood coagulation indexes, plasma prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), D-dimer (D-D), activated partial blood coagulation time (APTT) live enzymes in three groups.Results: (1) Compared with the non-pregnant group and late pregnant group, PLT was significantly lower, while the MPV and PDW were significantly higher in HDCP group; PLT in late pregnant group was significantly lower than that in non-pregnant group, and there were no significantly difference of MPV and PDW in the two groups; (2) Compared with the non-pregnant group and late pregnant group, PT and APTT levels were significantly lower, while FIB and D-D were significantly higher in HDCP group; The level of PT and APTT in late pregnant group were significantly lower, and FIB and D-D levels were significantly higher than that in non-pregnant group, However, The level of TT were no statistical significance difference among the three groups.Conclusion: HDCP existence phenomenon of platelet activation and apparent high coagulation state, dynamic detection of HDCP patients platelet parameters and blood coagulation indexes to prevent related complications, improve obstetrics safety is of great significance.

  17. Diagnostic value of platelet derived growth factor-BB, transforming growth factor-β1,matrix metalloproteinase-1, and tissue inhibitor of matrix metalloproteinase-1 in serum and peripheral blood mononuclear cells for hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Bin-Bin Zhang; Wei-Min Cai; Hong-Lei Weng; Zhong-Rong Hu; Jun Lu; Min Zheng; Rong-Hua Liu

    2003-01-01

    AIM: Noninvasive diagnosis of hepatic fibrosis has become the focus because of the limited biopsy, especially in the surveillance of treatment and in screening hepatic fibrosis.Recently, regulatory elements involved in liver fibrosis, such as platelet derived growth factor-BB (PDGF-BB), transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), have been studied extensively. To determine whether these factors or enzymes could be used as the indices for the diagnosis of hepatic fibrosis, we investigated them by means of receiver operating characteristic (ROC) curve.METHODS: Serum samples from sixty patients with chronic viral hepatitis B and twenty healthy blood donors were assayed to determine the level of PDGF-BB, TGF-β1, MMP-1, and TIMP-1 with ELISA, and HA, PCIII, C-IV, and LN level with RIA. The message RNA (mRNA) expression of TIMP-1 and MMP-1 in peripheral blood mononuclear cells (PBMCs) was detected by RT-PCR and Northern blot hybridization. Liver biopsy was performed in all patients.The biopsy samples were histopathologically examined. The trial was double-blind controlled.RESULTS: The serum level of PDGF-BB, TIMP-1, the ratio of TIMP-1 and MMP-1 (TIMP-1/MMP-1), mRNA expression of TIMP-1 (TIMP-1mRNA), and the ratio of TIMP-1mRNA and MMP-1mRNA (TIMP-1mRNA/MMP-1mRNA) in patients was significantly higher than those in the healthy blood donors (t=2.514-11.435, P=0.000-0.016). The serum level of PDGF-BB, TIMP-1, TIMP-1/MMP-1, and TIMP-1mRNA was positively correlated with fibrosis stage and inflammation grade (r=0.239-0.565, P=0.000-0.033), while the serum level of MMP-1 was negatively correlated with fibrosis stage and inflammation grade, and TIMP-1mRNA/MMP-1mRNA was positively correlated with inflammation grade. Through the analysis by ROC curve, serum PDGF-BB was the most valuable marker, and its sensitivity was the highest among the nine indices. The markers with the highest

  18. Plasma levels of plasminogen activator inhibitor type 1, factor VIII, prothrombin activation fragment 1+2, anticardiolipin, and antiprothrombin antibodies are risk factors for thrombosis in hemodialysis patients.

    Science.gov (United States)

    Molino, Daniela; De Santo, Natale G; Marotta, Rosa; Anastasio, Pietro; Mosavat, Mahrokh; De Lucia, Domenico

    2004-09-01

    Patients with end-stage renal disease are prone to hemorrhagic complications and simultaneously are at risk for a variety of thrombotic complications such as thrombosis of dialysis blood access, the subclavian vein, coronary arteries, cerebral vessel, and retinal veins, as well as priapism. The study was devised for the following purposes: (1) to identify the markers of thrombophilia in hemodialyzed patients, (2) to establish a role for antiphospholipid antibodies in thrombosis of the vascular access, (3) to characterize phospholipid antibodies in hemodialysis patients, and (4) to study the effects of dialysis on coagulation cascade. A group of 20 hemodialysis patients with no thrombotic complications (NTC) and 20 hemodialysis patients with thrombotic complications (TC) were studied along with 400 volunteer blood donors. Patients with systemic lupus erythematosus and those with nephrotic syndrome were excluded. All patients underwent a screening prothrombin time, activated partial thromboplastin time, fibrinogen (Fg), coagulation factors of the intrinsic and extrinsic pathways, antithrombin III (AT-III), protein C (PC), protein S (PS), resistance to activated protein C, prothrombin activation fragment 1+2 (F1+2), plasminogen, tissue type plasminogen activator (t-PA), plasminogen tissue activator inhibitor type-1 (PAI-1), anticardiolipin antibodies type M and G (ACA-IgM and ACA-IgG), lupus anticoagulant antibodies, and antiprothrombin antibodies type M and G (aPT-IgM and aPT-IgG). The study showed that PAI-1, F 1+2, factor VIII, ACA-IgM, and aPT-IgM levels were increased significantly over controls both in TC and NTC, however, they could distinguish patients with thrombotic complications from those without, being increased maximally in the former group. The novelty of the study is represented by the significant aPT increase that was observed in non-systemic lupus erythematosus hemodialysis patients, and particularly in those with thrombotic events. In addition

  19. 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.

  20. Novel determinants in coagulation pathophysiology: reappraising the role of β2-glycoprotein I, factor seven activating protease and protein S

    NARCIS (Netherlands)

    Dienava-Verdoold, I.

    2012-01-01

    Blood coagulation cascade ensures the arrest of bleeding and restoration of vascular integrity after physical damage and therefore is essential to normal physiology. However, many pathological conditions can disturb the tightly regulated haemostatic balance. Inflammation or malignancies may promote

  1. Rat Prostate Tumors Express Cancer Procoagulant, an Activator of Coagulation Factor X

    OpenAIRE

    Kamocka, Malgorzata; Pollard, Morris; Suckow, Mark; Wojciech P. Mielicki; Rosen, Elliot D.

    2008-01-01

    Two common procoagulant activities associated with tumors are tissue factor and cancer procoagulant (CP), an activator of coagulation factor X. We have identified a convenient source of CP in transplanted Lobund–Wistar rat PA3 prostate tumors. CP activity was purified from 5 independent transplanted prostate tumors by column chromatography. The protein activated factor X in the absence of TF and factor VII. An antihuman CP antibody recognized rat CP in an ELISA and inactivated CP activity in ...

  2. Proton-Pump Inhibitors Therapy and Blood Pressure Control

    OpenAIRE

    Juan Francisco Sánchez Muñoz-Torrero; Pedro Joya-Vazquez; M Asunción Bacaicoa; Raul Velasco; Jose L. Chicón; Sara Trejo; M. Antonia Carrasco; N. Roberto Robles

    2014-01-01

    Objective: To evaluate  the potential impact of inhibitors of proton-pump in blood-pressure. .Methods: In a 24-hour-ambulatory-blood-pressure-monitoring (AMBP)-database we analyzed records of 462-hypertensive-patients according Proton-Pump Inhibitors (PPI). 150(33%)-patients were regularly users of PPI, and 312(67%) nonusers of PPI. Ambulatory-blood-pressure was measured non-invasively for 24--hours by the Spacelab-devices programmed-to-measure every 20-minutes during-daytime and every 60-min...

  3. Factor Xa inhibitors: new anti-thrombotic agents and their characteristics.

    Science.gov (United States)

    Ieko, Masahiro; Tarumi, Takashi; Nakabayashi, Toru; Yoshida, Mika; Naito, Sumiyoshi; Koike, Takao

    2006-01-01

    Factor Xa (FXa) is a key enzyme that is positioned at the convergence of the intrinsic and extrinsic pathways in the blood coagulation cascade, and inactivation by a specific FXa inhibitor effectively prevents the generation of thrombin. Various types of low molecular weight (LMW) heparin, which function as semi-selective and indirect FXa inhibitors, are replacing unfractionated heparin (UFH) as agents for the prevention and treatment of venous thromboembolism (VTE), as well as in initial treatment for coronary events. Of those, heparinoid has been shown to be safer and more effective for the prevention of postoperative VTE than UFH, especially for treatment of heparin-induced thrombocytopenia (HIT). Further, synthetic pentasaccharide has been found to offer advantages over current thromboprophylactic regimens in a number of patients undergoing major orthopedic surgery. Other studies have shown that pentasaccharide is more effective for overall VTE in comparison with LMW heparin, though it was also associated with an increased rate of major bleeding. Synthetic, selective, and direct inhibitors to FXa, such as DX-9065a, are highly potent and orally bioavailable antithrombotic agents that have demonstrated an improved side effect profile, probably by allowing sufficient thrombin to remain for platelet activation and normal hemostasis, while preventing pathological thrombus formation. For thrombosis therapy, the most desirable type of antithrombotic agent is an orally active drug that has a broad range of effective doses and no hemorrhagic side effects. Presently, many types of direct inhibitors are in various stages of clinical trials and expected to provide significant benefits as compared to currently utilized therapy strategies. PMID:16146728

  4. Microfluidic Chip-Based Online Screening Coupled to Mass Spectrometry: Identification of Inhibitors of Thrombin and Factor Xa.

    Science.gov (United States)

    Iyer, Janaki Krishnamoorthy; Otvos, Reka A; Kool, Jeroen; Kini, R Manjunatha

    2016-02-01

    Thrombin and factor Xa (FXa) are critical enzymes of the blood coagulation cascade and are excellent targets of anticoagulant agents. Natural sources present an array of anticoagulants that can be developed as antithrombotic drugs. High-resolution, online screening techniques have been developed for the identification of drug leads from complex mixtures. In this study, we have developed and optimized a microfluidic online screening technique coupled to nano-liquid chromatography (LC) and in parallel with a mass spectrometer for the identification of thrombin and FXa inhibitors in mixtures. Inhibitors eluting from the nano-LC were split postcolumn in a 1:1 ratio; half was fed into a mass spectrometer (where its mass is detected), and the other half was fed into a microfluidic chip (which acts as a microreactor for the online assays). With our platform, thrombin and FXa inhibitors were detected in the assay in parallel with their mass identification. These methods are suitable for the identification of inhibitors from sample amounts as low as sub-microliter volumes. PMID:26323281

  5. Treating High Blood Pressure: Is an ACE Inhibitor Drug Right for You?

    Science.gov (United States)

    ... High Blood Pressure: Is an ACE Inhibitor Drug Right for You? What are ACE inhibitors? ACE inhibitors, ... talk with your doctor about which drugs are right for you. If your blood pressure is slightly ...

  6. Coagulation in patients with severe sepsis.

    Science.gov (United States)

    Levi, Marcel; Poll, Tom van der

    2015-02-01

    In the majority of patients with severe sepsis, systemic activation of coagulation is present. Increasing evidence points to an extensive cross-talk between coagulation and inflammation that may play an important role in the pathogenesis of sepsis. Inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Proinflammatory cytokines and other mediators are capable of activating the coagulation system and downregulating important physiological anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on expression of tissue factor on activated mononuclear cells and endothelial cells, and is insufficiently counteracted by TFPI. Simultaneously, endothelial-bound anticoagulant mechanism, in particular the protein C system, is shutoff by proinflammatory cytokines. In addition, fibrin removal is severely inhibited, because of inactivation of the fibrinolytic system, caused by an upregulation of its main inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Increased fibrin formation and impaired removal lead to (micro)vascular thrombosis, which may result in tissue ischemia and subsequent organ damage. The cornerstone of the management of coagulation in sepsis is the specific and vigorous treatment of the underlying disorder. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and initial clinical studies. Heparin may be an effective anticoagulant approach and alternative strategies comprise restoration of physiological anticoagulant pathways. PMID:25590524

  7. Prothrombotic coagulation defects and cardiovascular risk factors in young women with acute myocardial infarction

    NARCIS (Netherlands)

    Tanis, BC; Bloemenkamp, DGM; van den Bosch, MAAJ; Kemmeren, JM; Algra, A; van de Graaf, Y; Rosendaal, FR

    2003-01-01

    We investigated the effect of prothrombotic coagulation defects in combination with smoking and other conventional risk factors on the risk of myocardial infarction in young women. In 217 women with a first myocardial infarction before the age of 50 years and 763 healthy control women from a populat

  8. Coagulation Factor Xa inhibits cancer cell migration via LIMK1-mediated cofilin inactivation

    NARCIS (Netherlands)

    Borensztajn, Keren; Peppelenbosch, Maikel P.; Spek, C. Arnold

    2010-01-01

    Previously, we showed that activated coagulation factor X (FXa) inhibits migration of breast, lung and colon cancer cells. We showed that the effect of FXa on migration was protease-activated receptor (PAR)-1-dependent, but the subsequent cellular signaling routes remained elusive. In the current ma

  9. Factor Xa : at the crossroads between coagulation and signaling in physiology and disease

    NARCIS (Netherlands)

    Borensztajn, Keren; Peppelenbosch, Maikel P.; Spek, C. Arnold

    2008-01-01

    Activated factor Xa (FXa) is traditionally known as an important player in the coagulation cascade responsible for thrombin generation. Long considered a passive bystander, it is now evident that FXa exerts direct effects on a wide variety of cell types via activation of its two main receptors, prot

  10. Monoclonal antibodies to coagulation factor IX define a high-frequency polymorphism by immunoassays.

    OpenAIRE

    Smith, K. J.

    1985-01-01

    Monoclonal antibodies have been used to demonstrate a polymorphism of human plasma coagulation factor IX antigen in double antibody solid-phase immunoradiometric assays. This polymorphism is detected in an assay where a monoclonal antibody (A-1) adsorbed to microtiter wells is used to bind factor IX from diluted plasma samples. Plasma samples with the factor IX polymorphism have less than 0.2 U/ml of apparent antigen when tested with the A-1 antibody, while assays with other monoclonal antibo...

  11. Polymorphisms in the genes for coagulation factor II,V,VII in patients undergoing coronary angiography

    Institute of Scientific and Technical Information of China (English)

    徐耕; 金国栋; 傅国胜; 马骥; 单江; 王建安

    2003-01-01

    Objective: To determine whether polymorphisms in the genes for coagulation factor II,V, VII could predispose an individual to increase risk for coronary artery disease (CAD) and/or myocardial infarction (MI) in Chinese. Methods: We screened coagulation factor II(G20210A),V(G1691A),VII (R353Q and HVR4) genotype in 374 patients undergoing coronary angiography by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay. Results: The R353Q and HVR4 genotype of the factor VII distribution was in accordance with Hardy-Weinberg equilibrium. The frequencies of FVII genotype or allele did not show statistically significant differences between CAD group and controls or between male and female. The frequencies of the Q allele and (RQ+QQ) genotype were significantly higher among the CAD patients without myocardial infarction (MI) history than among those with MI history (P<0.05). However, HVR4 polymorphism was not significantly different within groups. We only find one normal control of factorII(G20210A) mutation. No coagulation factor V(G1691A) mutation was found in the CAD patients and controls. Conclusion: The factor II(G20210A),V(G1691A) mutation is absent and may not be a major genetic factor for CAD and/or MI; the Q allele of the R353Q polymorphism of the factor VII gene may be a protective genetic factor against myocardial infarction in Chinese.

  12. Risk Factors for High Blood Pressure

    Science.gov (United States)

    ... the NHLBI on Twitter. Risk Factors for High Blood Pressure Anyone can develop high blood pressure; however, age, ... can increase your risk for developing high blood pressure. Age Blood pressure tends to rise with age. About 65 ...

  13. Polymorphisms in the genes for coagulation factor Ⅱ,Ⅴ,Ⅶ in patients undergoing coronary angiography

    Institute of Scientific and Technical Information of China (English)

    徐耕; 金国栋; 傅国胜; 马骥; 单江; 王建安

    2003-01-01

    Objective: To determine whether polymorphisms in the genes for coagulation factor Ⅱ,Ⅴ,Ⅶ could predispose an individual to increase risk for coronary artery disease (CAD) and/or myocardial infarction (MI) in Chinese. Methods: We screened coagulation factor Ⅱ( G20210A),Ⅴ( G1691A),Ⅶ( R353Q and HVR4) genotype in 374 patients undergoing coronary angiography by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay. Results: The R353Q and HVR4 genotype of the factor Ⅶ distribution was in accordance with Hardy-Weinberg equilibrium. The frequencies of FVⅡ genotype or allele did not show statistically significant differences between CAD group and controls or between male and female.The frequencies of the Q allele and ( RQ + QQ) genotype were significantly higher among the CAD patients without myocardial infarction (MI) history than among those with MI history (P < 0.05). However, HVR4 polymorphism was not significantly different within groups. We only find one normal control of factorⅡ(G20210A) mutation. No coagulation factor Ⅴ(G1691A) mutation was found in the CAD patients and con-trois. Conclusion: The factor Ⅱ(G20210A),Ⅴ(G1691A) mutation is absent and may not be a major genetic factor for CAD and/or MI; the Q allele of the R353Q polymorphism of the factor Ⅶ gene may be a protective genetic factor against myocardial infarction in Chinese.

  14. 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.

  15. Massive exploration of perturbed conditions of the blood coagulation cascade through GPU parallelization.

    Science.gov (United States)

    Cazzaniga, Paolo; Nobile, Marco S; Besozzi, Daniela; Bellini, Matteo; Mauri, Giancarlo

    2014-01-01

    The introduction of general-purpose Graphics Processing Units (GPUs) is boosting scientific applications in Bioinformatics, Systems Biology, and Computational Biology. In these fields, the use of 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.

  16. [New oral anticoagulants - influence on coagulation tests].

    Science.gov (United States)

    Simeon, L; Nagler, M; Wuillemin, W A

    2014-01-01

    The new oral anticoagulants (NOACs) represent alternative antithrombotic agents for prophylaxis and therapy of thromboembolic diseases. They act either by inhibition of the clotting factor Xa or IIa (thrombin). As a consequence, they influence several coagulation assays (for example prothrombin time, activated partial thromboplastin time). Because of the short half-life of these new agents, these changes show great variations in the course of 24 hours. Furthermore, there are significant differences of laboratory results depending on the used reagents. We explain the influence of apixaban, rivaroxaban (factor Xa inhibitors) and dabigatran (thrombin inhibitor) on the most commonly used coagulation assays. Besides we show that this influence depends on the way of action of the drug as well as on the principle of the coagulation assay. Being aware of this relationships helps to interpret the results of coagulation assays under influence of NOACs correctly.

  17. 肺癌患者凝血功能与肺癌分期的关系%The Relationship Between Blood Coagulation Function and Lung Cancer Staging

    Institute of Scientific and Technical Information of China (English)

    何丽钦; 钟可芳

    2012-01-01

    Objective To explore the relationship between the function of blood coagulation in patients with lung cancer and lung cancer staging. Methods EIISA assay for detection of 140 cases of advanced malignant tumor patients and 30 cases of normal human blood coagulation and anticoagulation activity related to laboratory indexes, including plasma fibrinogen ( Fb) , antithrombin III( AT-III) , von Willebrand factor ( Vwf ) , D-D ( D-dimer ). Results The patients with advanced malignant plasma D- dimer, fibrinogen, thrombin antithrombin III and von Willebrand factor antigen levels were significantly elevated and indexes in patients with lung cancer clinical staging with increased. Conclusion The patients with lung cancer usually presence of coagulation, anticoagulation and activation of fibrinolytic system, exists high coagulation state, thus, high coagulation state and clinical staging of lung cancer was positively related to.%目的 探讨肺癌患者凝血功能与肺癌分期的关系.方法 采用ELISA、免疫比浊法检测140例晚期恶性肿瘤患者和30例正常人的凝血、抗凝活性相关的实验室指标,包括血浆纤维蛋白原( Fb),抗凝血酶Ⅲ (AT-Ⅲ),血管性血友病因子 ( vWF),D-二聚体( D-D).结果 晚期恶性肿瘤患者的血浆D-D、Fb、AT-Ⅲ、vWF抗原的水平较正常人显著升高;在肺癌Ⅲ期、Ⅳ期与Ⅰ期相比明显增高(P<0.05),差异有统计学意义;Ⅱ期与Ⅰ期相比增高不明显(P>0.05),差异没有统计学意义.结论 肺癌患者存在凝血、抗凝、纤溶系统的激活,机体呈现高凝状态,并且高凝状态与肺癌临床分期呈正相关.

  18. Influence of red blood cell concentration on the initiation time of blood coagulation: risk of thrombus formation in pregnant females with anemia.

    Science.gov (United States)

    Sagesaka, Toshiaki; Juen, Hiroyasu; Hayashi, Masatoshi

    2007-01-01

    The influence of a change in red blood cell (RBC) concentration on the initiation time of blood coagulation (Ti) in pregnant and non-pregnant females was investigated using a damped oscillation rheometer to evaluate the risk of hemorrhagic tendency or thrombus formation. The blood samples from 40 female volunteers (20 pregnants and 20 non-pregnants) were examined. After centrifuging some portion of each blood sample, an appropriate volume was taken from the RBC layer to make an artificially diluted blood, or to add it to the autologous blood, making an artificially concentrated blood. The Ti of non-pregnant females was significantly reduced with increasing the RBC concentration from 3.75+/-0.25 to (5.75+/-0.25)x10(6)/mm(3). However, the Ti of pregnant females showed almost no change in the RBC concentrations from 3.25+/-0.25 to (5.25+/-0.25)x10(6)/mm(3). These results suggest that RBC concentration plays an important role in accelerating the initial coagulation reaction of blood of non-pregnant females and that a hypercoagulant condition caused by pregnancy conceals the effect that changes in RBC concentration have in pregnant females. PMID:17325439

  19. EPAS1/HIF-2 alpha-mediated downregulation of tissue factor pathway inhibitor leads to a pro-thrombotic potential in endothelial cells.

    Science.gov (United States)

    Stavik, Benedicte; Espada, Sandra; Cui, Xue Yan; Iversen, Nina; Holm, Sverre; Mowinkel, Marie-Christine; Halvorsen, Bente; Skretting, Grethe; Sandset, Per Morten

    2016-04-01

    Neovascularization and hemorrhaging are evident in advanced atherosclerotic plaques due to hypoxic conditions, and mediate the accumulation of metabolic substrates, inflammatory cells, lipids, and other blood born factors inside the plaque. Tissue factor (TF) pathway inhibitor (TFPI) is mainly expressed by endothelial cells and is the endogenous inhibitor of the coagulation activator TF, which together with the downstream product thrombin can drive plaque progression and atherogenesis. We aimed to investigate the effect of hypoxic conditions on endothelial cell expression and activity of TFPI and TF that are important in coagulation initiation. Hypoxia was induced in primary human umbilical vein endothelial cells using chemicals or 1% oxygen tension, and mRNA and protein expressions were measured using qRT-PCR, ELISA, and Western blot analysis. Microscopy of fluorescence-labeled cells was used to visualize cell-associated TFPI. Cell-surface factor Xa (FXa) activity was measured using a two-stage chromogenic substrate method. We found that hypoxia reduced the TFPI mRNA and protein levels and increased the TF mRNA expression in a dose-dependent manner. The effect on TFPI was apparent on all the protein pools of TFPI, i.e., secreted TFPI, cell-surface associated TFPI, and intracellular TFPI, and seemed to be dependent upon hypoxia inducible factor-2α (HIF-2α). An increase in FXa activity was also observed on the endothelial cell surface, reflecting an increase in pro-thrombotic potential of the cells. Our findings indicate that hypoxic conditions may enhance the pro-coagulant activity of endothelial cells, which may promote atherogenesis in addition to clinical events and thus the severity of atherosclerotic disorders. PMID:26826018

  20. Neutralisation of factor VIII inhibitors by anti-idiotypes isolated from phage-displayed libraries.

    Science.gov (United States)

    Schmidt, Anja; Brettschneider, Kerstin; Kahle, Jörg; Orlowski, Aleksander; Becker-Peters, Karin; Stichel, Diana; Schulze, Jörg; Braner, Markus; Tampé, Robert; Schwabe, Dirk; Königs, Christoph

    2016-07-01

    Following replacement therapy with coagulation factor VIII (FVIII), up to 30 % of haemophilia A patients develop FVIII-specific inhibitory antibodies (FVIII inhibitors). Immune tolerance induction (ITI) is not always successful, resulting in a need for alternative treatments for FVIII inhibitor-positive patients. As tolerance induction in the course of ITI appears to involve the formation of anti-idiotypes specific for anti-FVIII antibodies, such anti-idiotypes might be used to restore haemostasis in haemophilia A patients with FVIII inhibitors. We isolated anti-idiotypic antibody fragments (scFvs) binding to murine FVIII inhibitors 2-76 and 2-77 from phage-displayed libraries. FVIII inhibitor/anti-idiotype interactions were very specific as no cross-reactivity with other FVIII inhibitors or isotype controls was observed. ScFvs blocked binding of FVIII inhibitors to FVIII and neutralised their cognate inhibitors in vitro and a monoclonal mouse model. In addition, scFv JkH5 specific for FVIII inhibitor 2-76 stained 2-76-producing hybridoma cells. JkH5 residues R52 and Y226, located in complementary determining regions, were identified as crucial for the JkH5/2-76 interaction using JkH5 alanine mutants. SPR spectroscopy revealed that JkH5 interacts with FVIII inhibitor 2-76 with nanomolar affinity. Thus, FVIII inhibitor-specific, high-affinity anti-idiotypes can be isolated from phage-displayed libraries and neutralise their respective inhibitors. Furthermore, we show that anti-idiotypic scFvs might be utilised to specifically target inhibitor-specific B cells. Hence, a pool of anti-idiotypes could enable the reestablishment of haemostasis in the presence of FVIII inhibitors in patients or even allow the depletion of inhibitors by targeting inhibitor-specific B cell populations. PMID:27009573

  1. 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

  2. Adrenal gland infection by serotype 5 adenovirus requires coagulation factors.

    Directory of Open Access Journals (Sweden)

    Lucile Tran

    Full Text Available Recombinant, replication-deficient serotype 5 adenovirus infects the liver upon in vivo, systemic injection in rodents. This infection requires the binding of factor X to the capsid of this adenovirus. Another organ, the adrenal gland is also infected upon systemic administration of Ad, however, whether this infection is dependent on the cocksackie adenovirus receptor (CAR or depends on the binding of factor X to the viral capsid remained to be determined. In the present work, we have used a pharmacological agent (warfarin as well as recombinant adenoviruses lacking the binding site of Factor X to elucidate this mechanism in mice. We demonstrate that, as observed in the liver, adenovirus infection of the adrenal glands in vivo requires Factor X. Considering that the level of transduction of the adrenal glands is well-below that of the liver and that capsid-modified adenoviruses are unlikely to selectively infect the adrenal glands, we have used single-photon emission computed tomography (SPECT imaging of gene expression to determine whether local virus administration (direct injection in the kidney could increase gene transfer to the adrenal glands. We demonstrate that direct injection of the virus in the kidney increases gene transfer in the adrenal gland but liver transduction remains important. These observations strongly suggest that serotype 5 adenovirus uses a similar mechanism to infect liver and adrenal gland and that selective transgene expression in the latter is more likely to be achieved through transcriptional targeting.

  3. Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains

    Energy Technology Data Exchange (ETDEWEB)

    Wun, T.C.; Kretzmer, K.K.; Girard, T.J.; Miletich, J.P.; Broze, G.J. Jr.

    1988-05-05

    Human plasma contains a lipoprotein-associated coagulation inhibitor (LACI) which inactivates factor X/sub a/ directly, and in a X/sub a/-dependent fashion also inhibits the VII/sub a/-tissue factor complex of the extrinsic coagulation pathway. Rabbit polyclonal anti-LACI antiserum was used to screen human placental and fetal liver lambdagt11 cDNA libraries for the expression of LACI antigens. Immunologically positive clones were further tested for their ability to bind /sup 125/I-factor X/sub a/. Seven clones were obtained which are immunologically and functionally active. The longest cDNA insert (lambdaP9) of these isolates is 1.4 kilobases (kb) while other clones are 1.0 kb in length. Nucleotide sequence analysis shows that lambdaP9 consists of 1431 bases that include a 5'-noncoding sequence of 132 nucleotides, an open reading frame of 912 nucleotides, and a 3'-noncoding region of 387 nucleotides. The predicted sequence of mature LACI contains 18 cysteines and three potential N-linked glycosylation sites. The amino acid sequence analysis of purified LACI's NH/sub 2/ terminus and two of its proteolytic fragments match exactly those deduced from the cDNA sequence, indicating that the cDNA codes for LACI. The translated amino acid sequence of LACI shows several discernible domains, including a highly negatively charged NH/sub 2/ terminus, three tandem Kunitz-type inhibitory domains, and a highly positively charged carboxyl terminus. Northern blot analysis shows that the following liver-derived cell lines, Chang liver, HepG2 hepatoma, and SK hepatoma all, contain two major species of mRNA which hybridize with LACI cDNA.

  4. SEPSIS-ASSOCIATED DISSEMINATED INTRAVASCULAR COAGULATION AND THROMBOEMBOLIC DISEASE

    Directory of Open Access Journals (Sweden)

    Nicola Semeraro

    2010-08-01

    Full Text Available Sepsis is almost invariably associated with haemostatic abnormalities ranging from subclinical activation of blood coagulation (hypercoagulability, which may contribute to localized venous thromboembolism, to acute disseminated intravascular coagulation (DIC, characterized by massive thrombin formation and widespread microvascular thrombosis, partly responsible of the multiple organ dysfunction syndrome (MODS, and subsequent consumption of platelets and coagulation proteins causing, in most severe cases, bleeding manifestations. There is general agreement that the key event underlying this life-threatening sepsis complication is the overwhelming inflammatory host response to the infectious agent leading to the overexpression of inflammatory mediators. Mechanistically, the latter, together with the micro-organism and its derivatives, causes DIC by 1 up-regulation of procoagulant molecules, primarily tissue factor (TF, which is produced mainly by stimulated monocytes-macrophages and by specific cells in target tissues; 2 impairment of physiological anticoagulant pathways (antithrombin, protein C pathway, tissue factor pathway inhibitor, which is orchestrated mainly by dysfunctional endothelial cells (ECs; and 3 suppression of fibrinolysis due to increased plasminogen activator inhibitor-1 (PAI-1 by ECs and likely also to thrombin-mediated  activation of thrombin-activatable fibrinolysis inhibitor (TAFI. Notably, clotting enzymes non only lead to microvascular thrombosis but can also elicit cellular responses that amplify the inflammatory reactions. Inflammatory mediators can also cause, directly or indirectly, cell apoptosis or necrosis and recent evidence indicates that products released from dead cells, such as nuclear proteins (particularly extracellular histones, are able to propagate further inflammation, coagulation, cell death and MODS. These insights into the pathogenetic mechanisms of DIC and MODS may have important implications for the

  5. Platelet Surface-Associated Activation and Secretion-Mediated Inhibition of Coagulation Factor XII

    OpenAIRE

    Zakharova, Natalia V.; Artemenko, Elena O.; Podoplelova, Nadezhda A.; Anastasia N Sveshnikova; Demina, Irina A.; Ataullakhanov, Fazly I.; Panteleev, Mikhail A.

    2015-01-01

    Coagulation factor XII (fXII) is important for arterial thrombosis, but its physiological activation mechanisms are unclear. In this study, we elucidated the role of platelets and platelet-derived material in fXII activation. FXII activation was only observed upon potent platelet stimulation (with thrombin, collagen-related peptide, or calcium ionophore, but not ADP) accompanied by phosphatidylserine exposure and was localised to the platelet surface. Platelets from three patients with grey p...

  6. A comparative study of the effect of continuous combined conjugated equine estrogen plus medroxyprogesterone acetate and tibolone on blood coagulability

    DEFF Research Database (Denmark)

    Skouby, SO; Sidelmann, JJ; Nilas, Lisbeth;

    2007-01-01

    in the tibolone group than in the CEE/MPA group. Both doses of tibolone increased APC-R significantly (P pathway inhibitor (TFPI) was lower in the CEE/MPA group than in the tibolone group (67.8 versus 79.9 ng ml(-1); P = 0.03). CEE/MPA reduced the concentration of antithrombin (P = 0.......002), protein S (P coagulability than CEE/MPA and has a potentially favourable effect on APC-R. This may translate...

  7. Pharmacokinetics of the direct factor Xa inhibitor edoxaban and digoxin administered alone and in combination.

    Science.gov (United States)

    Mendell, Jeanne; Noveck, Robert J; Shi, Minggao

    2012-10-01

    The oral anticoagulant edoxaban, a factor Xa inhibitor, will likely be coadministered with digoxin in some patients with atrial fibrillation. Both drugs are substrates for P-glycoprotein. The objective of this phase 1, parallel study was to assess the effects of coadministration of both drugs on their respective pharmacokinetics (PK) and pharmacodynamics (PD). Forty-eight subjects, aged 18 to 45 years, received either edoxaban 60 mg once daily × 7 days (n = 24) or digoxin 0.25 mg twice daily × 2 days and once daily × 5 days (n = 24) and then concomitantly for 7 days. Serial blood and urine samples were collected for digoxin and edoxaban concentrations on days 7 and 14. Serial coagulation assays were measured for edoxaban on days 7 and 14. Edoxaban PK parameters demonstrated mild increases in area under the curve and peak concentrations of 9.5% and 15.6%, respectively, when coadministered with digoxin. Although digoxin PK parameters demonstrated increased area under the curve and peak concentrations of 8.3% and 28%, respectively, plasma concentrations were within the established therapeutic range. Edoxaban PD were consistent with PK. Both drugs were well tolerated alone or in combination. No clinically significant changes in PK, PD, or renal elimination were observed with concomitant administration of edoxaban and digoxin. PMID:23064240

  8. 妊娠期高血压疾病患者凝血和抗凝因子的变化及意义%Change and significance of coagulation factors and anti-coagulation factors in patients with hypertensive disorder complicating pregnancy

    Institute of Scientific and Technical Information of China (English)

    陈莉; 沈晓露; 叶玲丽

    2012-01-01

    Objective; To explore the change and significance of coagulation factors and anti - coagulation factors in patients with hypertensive disorder complicating pregnancy (HDCP) .Methods; The contents of coagulation factors Ⅷ: C,Ⅸ: C, AT: C, and VWF; Ag of 80 patients with HDCP (HDCP group) and 25 normal pregnant women (control group) were detected by STA - R automatic blood coagulation meter. Results: The contents of coagulation factors Ⅷ: C, Ⅸ: C, and VWF: Ag in HDCP group were higher than those in control group (P <0. 05 or P <0. 01) ; while the content of AT; C in HDCP group was lower than that in control group ( P <0. 05 or P < 0.01) .Conclusion; Detecting coagulation factors Ⅷ: C,Ⅸ: C, AT: C, and VWF: Ag has a certain clinical significance for diagnosis and treatment of HDCP.%目的:探讨妊高征患者凝血和抗凝因子的变化及意义.方法:采用STA-R自动血凝仪分别检测80例妊娠期高血压疾病患者(妊高征组)、25例正常孕妇(对照组)的凝血因子Ⅷ:C、Ⅸ:C、AT(抗凝血酶):C及VWF(血小板表面受体)抗原含量.结果:妊高征组凝血因子Ⅷ:C、Ⅸ:C及VWF:Ag均明显高于对照组(P<0.05或P<0.01);妊高征组AT:C明显低于对照组(P<0.05或P<0.01).结论:检测凝血因子Ⅷ:C、Ⅸ:C、AT:C及VWF:Ag对诊治妊高征有一定的临床意义.

  9. Correction of disorders in tissue perfusion, blood coagulation and fibrinolysis with Orbita apparatus on terahertz waves of cell metabolites

    Directory of Open Access Journals (Sweden)

    Vyacheslav F. Kirichuk

    2013-02-01

    Full Text Available This article contains information on principle of operation, technical parameters and possible application of Orbita {transliteration from Russian} apparatus for hemodynamic, fibrinolytic and peripheral perfusion disorders treatment. A single exposure to terahertz waves emitted by Orbita apparatus, corresponding to frequencies of molecular absorption and emission spectra of atmospheric oxygen (129.0 GHz, completely cures coagulant and fibrinolytic disorders of animals with acute immobilization stress. A course of treatment with electromagnetic waves corresponding to frequencies of molecular absorption and emission spectra of nitrogen oxide (150.176 – 150.664 leads to normalization of disrupted peripheral tissue perfusion parameters of animal undergoing treatment and stimulates basal and induced output of nitrogen oxide. This leads to decrease in peripheral vascular resistance to microcirculation and increase in blood flow to microvasculature. Experimental data provided in this article serves as a proof of viability of Orbita apparatus for treatment of coagulant, fibrinolytic and tissue perfusion disorders.

  10. Imbalance of pro- vs. anti-coagulation factors in Chinese patients with Budd-Chiari syndrome and non-cirrhotic portal vein thrombosis.

    Directory of Open Access Journals (Sweden)

    Hui Chen

    Full Text Available The coagulation abnormalities in non-cirrhotic Budd-Chiari syndrome (NC-BCS and non-cirrhotic portal vein thrombosis (NC-PVT are unclear. We conducted this case-control study to investigate the coagulation profile of NC-BCS and NC-PVT in Chinese patients.We measured the levels of factors II, V, VII, VIII, IX, X, XI, XII, protein C (PC, protein S (PS and antithrombin (AT in blood samples from 37 NC-BCS patients, 74 NC-PVT patients, and 100 healthy controls. The levels and ratios of pro- and anti-coagulation factors were compared between patients with NC-BCS and healthy controls, between different types of NC-BCS and between NC-PVT and healthy controls.In patients with NC-BCS, factor VIII (P<0.001 was significantly elevated; factor V (P<0.001, VII (P<0.001, IX (P = 0.003, X (P<0.001, XI (P<0.001, XII (P<0.001, PC (P<0.001 and AT (P<0.001 were significantly decreased; and no difference was observed for factor II (P = 0.088 and PS (P = 0.199 compared with healthy controls. Factor VIII-to-PC (P = 0.008, factor VIII-to-PS (P = 0.037 and factor VIII-to-AT (P = 0.001 were significantly increased; other ratios were significantly reduced or did not show any difference. No differences were observed between different types of NC-BCS for individual pro- and anti-coagulation factors or the ratios between them. Among patients with NC-PVT, factor VIII (P<0.001 was significantly elevated and other factors were significantly decreased. Factor II-to-PC (P<0.001, factor VIII-to-PC (P<0.001, factor IX-to-PC (P<0.001, factor VIII-to-PS (P<0.001, factor II-to-AT (P<0.001, factor VIII-to-AT (P<0.001 and factor IX-to-AT (P<0.001 were significantly increased; all other ratios for NC-PVT were significantly reduced or did not show any significant difference.NC-BCS and NC-PVT are associated with elevated levels of factor VIII and the decreased levels of PC and AT were probably the most significant features of coagulation imbalance. Additionally, NC-PVT was associated with

  11. Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk

    NARCIS (Netherlands)

    H. Zhang; E.C. Löwenberg; J.R. Crosby; A.R. Macleod; C. Zhao; D. Gao; C. Black; A.S. Revenko; J.C.M. Meijers; E.S. Stroes; M. Levi; B.P. Monia

    2010-01-01

    Existing anticoagulants effectively inhibit the activity of coagulation factors of the extrinsic and common pathway but have substantial limitations and can cause severe bleeding complications. Here we describe a novel therapeutic approach to thrombosis treatment. We have developed and characterized

  12. Coagulation factor Va binds to human umbilical vein endothelial cells and accelerates protein C activation.

    OpenAIRE

    Maruyama, I.; Salem, H H; Majerus, P W

    1984-01-01

    In vitro the rate of protein C activation by thrombin is significantly accelerated by two distinct cofactors (a) the endothelial cell surface protein, thrombomodulin, and (b) human coagulation Factor Va. We have recently reported that the activity of Factor Va is contained in the 78,000-D light chain. In this study we have investigated the effects of Factor Va and its light chain on the activation of protein C in the presence of cultured endothelial cells. Thrombin-catalyzed protein C activat...

  13. A primary study on the relationship between tissue factor, tissue factor pathway inhibitor and obstetric coagulation system%组织因子、组织因子途径抑制物与产科凝血关系的初步研究

    Institute of Scientific and Technical Information of China (English)

    李少芬; 刘燕儒; 张慧英; 赵芳

    2007-01-01

    目的 检测正常足月妊娠胎盘、蜕膜和子宫肌层中组织因子(tissue factor,TF)和组织因子途径抑制物(tissue factor pathway inhibitor,TFPI)含量,探讨TF、TFPI与产科凝血间的关系.方法 选择正常足月妊娠孕妇30例,用ELISA方法分别检测血浆、胎盘、蜕膜、子宫肌层中TF、TFPI抗原含量.结果 胎盘、蜕膜和子宫肌层中TF抗原含量分别为(14.17±0.60)ng/mg总蛋白、(15.60±0.75)ng/mg总蛋白和(4.37±1.28)ng/mg总蛋白.TFPI抗原含量分别为(11.15±3.63)ng/mg总蛋白、(39.17±15.32)ng/mg总蛋白和(8.91±10.00)ng/mg总蛋白.血浆中TF、TFPI分别为0.013 ng/mg总蛋白和(34.00±10.75)ng/mg总蛋白. 结论正常足月妊娠胎盘、蜕膜和子宫肌层的高TF,低TFPI抗原水平可能与胎盘剥离面凝血止血及产科凝血障碍有关.

  14. 临产凝血四项检测与产时失血量的相关性研究%Research on the Relationship Between the Detection of 4 Indicators of Blood Coagulation and Blood Loss in Labor

    Institute of Scientific and Technical Information of China (English)

    梁荣伟; 兰枝; 杨善业; 刘新雄; 宁儒凤

    2012-01-01

    [Objective] To explore the relationship between 4 indicators of blood coagulation and blood loss of pregnant women during the labor. [Methods]Totally 2000 pregnant women in obstetric department of our hospital were selected and divided into natural delivery group and cesarean section group with 1000 cases in each group. Prenatal automated coagulation analyzer was used to detect 4 indicators of blood coagulation. Maternal bleeding volume of parturients at labor was estimated by obstetricians. The relationship between 4 indicators of blood coagulation and blood loss was analyzed. [Results] There was no relationship between 4 indicators of blood coagulation at labor and blood loss during natural delivery and cesarean section( P >0. 05) , while the abnormal rate of 4 prenatal indicators of blood coagulation had obvious relation with intrapartum hemorrhage( P 0.05),而产前凝血四项结果异常率与产时出血量多少有明显的相关性(P<0.05);同一孕妇四项结果异常项目越多产程大出血的几率越高.[结论]产前凝血四项结果异常率与产时出血量有一定的相关性,同一孕妇四项结果异常率与出血量明显相关,临床应给予高度重视.

  15. 分娩方式与不同体重新生儿凝血四项的研究%Study on 4 items of blood coagulation in neonates with childbirth fashions and different body weights

    Institute of Scientific and Technical Information of China (English)

    黄伟东; 梁贵方; 郭小芳; 方文; 梁永钊; 胡玉转; 何美巧

    2012-01-01

    Objective To probe into the relationship among the 4 items of blood coagulation with the childbirth fashions and the body weights in neonates.The clinical reference basis was provided to analyze the blood coagulation physiology and influence factors in neonates.Methods The 4 items of blood coagulation,which included prothrombin time (PT),activated partial thromboplastin time (APTT),fibrinogen (FIB) and thrombin time (TT),were determined in plasma for 644 neonates with different childbirth fashions and different body weights.Results Compared with control group,the 4 items of blood coagulation in the first groups (<1500 g) of natural childbirth and caesarean section group for neonates with different body weights were all obviously extended (P<0.01); PT,APTT was extended (P<0.05) and TT,FIB was not apparently changed (P>0.05) for second group (1500~2500 g),the 4 items of blood coagulation were all not apparendy changed (P>0.05) for fourth group (>4000 g).First group of to cut the belly open childbirth was compared with first group of natural childbirth,PT,APTT is extended (P<0.05) and TT,FIB is not changed (P>0.05).The 4 items of blood coagulation are not apparently changed (P>0.05) for other corresponding body weights in caesarean section group and natural childbirth.Conclusions The 4 items of blood coagulation of neonates are affected by body weights.The smaller the body weights,the longer time of the blood coagulation.The blood coagulation times gradually shorten with the increasing body weight,but with FIB gradually increased.The childbirth fashions affect the blood coagulation neonates with the weight <1500 g.%目的 探讨新生儿凝血四项功能与分娩方式、体重的关系,分析新生儿凝血生理及其影响因素,为临床提供参考依据.方法 取644例不同分娩方式和体重的新生儿的血浆进行凝血四项即凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)和凝

  16. SV-IV Peptide1–16 reduces coagulant power in normal Factor V and Factor V Leiden

    Science.gov (United States)

    Di Micco, Biagio; Lepretti, Marilena; Rota, Lidia; Quaglia, Ilaria; Ferrazzi, Paola; Di Micco, Gianluca; Di Micco, Pierpaolo

    2007-01-01

    Native Factor V is an anticoagulant, but when activated by thrombin, Factor X or platelet proteases, it becomes a procoagulant. Due to these double properties, Factor V plays a crucial role in the regulation of coagulation/anticoagulation balance. Factor V Leiden (FVL) disorder may lead to thrombophilia. Whether a reduction in the activation of Factor V or Factor V Leiden may correct the disposition to thrombophilia is unknown. Therefore we tested SV-IV Peptide 1–16 (i.e. a peptide derived by seminal protein vescicle number IV, SV-IV) to assess its capacity to inhibit the procoagulant activity of normal clotting factor V or Factor V Leiden (FVL). We found that SV-IV protein has potent anti-inflammatory and immunomodulatory properties and also exerts procoagulant activity. In the present work we show that the SV-IV Peptide 1–16, incubated with plasma containing normal Factor V or FVL plasma for 5 minutes reduces the procoagulant capacity of both substances. This is an anticoagulant effect whereas SV-IV protein is a procoagulant. This activity is effective both in terms of the coagulation tests, where coagulation times are increased, and in terms of biochemical tests conducted with purified molecules, where Factor X activation is reduced. Peptide 1–16 was, in the pure molecule system, first incubated for 5 minutes with purified Factor V then it was added to the mix of phosphatidylserine, Ca2+, Factor X and its chromogenic molecule Chromozym X. We observed a more than 50% reduction in lysis of chromogenic molecule Chromozym X by Factor Xa, compared to the sample without Peptide 1–16. Such reduction in Chromozym X lysis, is explained with the reduced activation of Factor X by partial inactivation of Factor V by Peptide 1–16. Thus our study demonstrates that Peptide 1–16 reduces the coagulation capacity of Factor V and Factor V Leiden in vitro, and, in turn, causes factor X reduced activation. PMID:18154667

  17. SV-IV Peptide1–16 reduces coagulant power in normal Factor V and Factor V Leiden

    Directory of Open Access Journals (Sweden)

    Ferrazzi Paola

    2007-12-01

    Full Text Available Abstract Native Factor V is an anticoagulant, but when activated by thrombin, Factor X or platelet proteases, it becomes a procoagulant. Due to these double properties, Factor V plays a crucial role in the regulation of coagulation/anticoagulation balance. Factor V Leiden (FVL disorder may lead to thrombophilia. Whether a reduction in the activation of Factor V or Factor V Leiden may correct the disposition to thrombophilia is unknown. Therefore we tested SV-IV Peptide 1–16 (i.e. a peptide derived by seminal protein vescicle number IV, SV-IV to assess its capacity to inhibit the procoagulant activity of normal clotting factor V or Factor V Leiden (FVL. We found that SV-IV protein has potent anti-inflammatory and immunomodulatory properties and also exerts procoagulant activity. In the present work we show that the SV-IV Peptide 1–16, incubated with plasma containing normal Factor V or FVL plasma for 5 minutes reduces the procoagulant capacity of both substances. This is an anticoagulant effect whereas SV-IV protein is a procoagulant. This activity is effective both in terms of the coagulation tests, where coagulation times are increased, and in terms of biochemical tests conducted with purified molecules, where Factor X activation is reduced. Peptide 1–16 was, in the pure molecule system, first incubated for 5 minutes with purified Factor V then it was added to the mix of phosphatidylserine, Ca2+, Factor X and its chromogenic molecule Chromozym X. We observed a more than 50% reduction in lysis of chromogenic molecule Chromozym X by Factor Xa, compared to the sample without Peptide 1–16. Such reduction in Chromozym X lysis, is explained with the reduced activation of Factor X by partial inactivation of Factor V by Peptide 1–16. Thus our study demonstrates that Peptide 1–16 reduces the coagulation capacity of Factor V and Factor V Leiden in vitro, and, in turn, causes factor X reduced activation.

  18. Coagulation Changes During Graded Orhostatic Stress and Recovery

    Science.gov (United States)

    Goswami, Nandu; Cvirn, Gerhard; Schlagenhauf, Aaxel; Leschnik, Bettina; Koestenberger, Martin; Roessler, Andreas; Jantscher, Andreas; Waha, James Elvis; Wolf, Sabine; Vrecko, Karoline; Juergens, Guenther; Hinghofer-Szalkay, Helmut

    2013-02-01

    Background: Orthostatic stress has been introduced as a novel paradigm for activating the coagulation system. We examined whether graded orthostatic stress (using head up tilt, HUT + lower body negative pressure, LBNP) until presyncope leads to anti / pro-coagulatory changes and how rapidly they return to baseline during recovery. Methodology: Eight male subjects were enrolled in this study. Presyncopal runs were carried out using HUT + LBNP. At minute zero, the tilt table was brought from 0° (supine) to 70 ° head-up position for 4 min, after which pressure in the LBNP chamber was reduced to -15, -30, and -45 mm Hg every 4 min. At presyncope, the subjects were returned to supine position. Coagulatory responses and plasma mass density (for volume changes) were measured before, during and 20 min after the orthostatic stress. Whole blood coagulation was examined by means of thrombelastometry. Platelet aggregation in whole blood was examined by using impedance aggregometry. Thrombin generation parameters, prothrombin levels, and markers of endothelial activation were measured in plasma samples. Results: At presyncope, plasma volume was 20 % below the initial supine value. Blood cell counts, prothrombin levels, thrombin peak, endogenous thrombin potential (ETP), and tissue factor pathway inhibitor (TFPI) levels increased during the protocol, commensurate with hemoconcentration. The markers of endothelial activation (tissue factor, TF, tissue plasminogen activator, t-PA) and the markers of thrombin generation (Prothrombin fragments 1 and 2, F1+2, and thrombin-antithrombin complex, TAT) increased significantly. During recovery, all the coagulation parameters returned to initial supine values except F1 +2 and TAT. Conclusion: Head-up tilt/LBNP leads to activation of the coagulation system. Some of the markers of thrombin formation are still at higher than supine levels during recovery.

  19. Effect of artificial colloids on blood coagulation during shock stage of severe burn injury

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jian-jun; XING Nan; CHEN Jiong; SHI Jian-wu; SU Guo-liang

    2013-01-01

    Background There are controversies about the use of artificial colloids.This research was aimed to determine the effect of various artificial colloids on blood coagulation in the shock stage of severe burn injury.Methods Totally,18 female Ba-Ma mini-pigs were subjected to a 40% total body surface third-degree flame burn under anesthesia.Resuscitation therapy was applied 2 hours after the injury,using the burn shock fluid resuscitation formula commonly accepted in the surgical treatment of burns.The Ba-Ma mini-pigs were randomly assigned to three groups (six pigs in each group):succinylated gelatin group (the artificial colloid used was succinylated gelatin Injection),hydroxyethyl starch group (the artificial colloid used was hydroxyethyl starch (130/0.4)),and allogeneic plasma group (the colloid used was allogeneic plasma).Blood samples were collected from the animals prior to the burn injury and again at intervals of 4,8,24 and 48 hours post-injury.The platelet count (PLT),prothrombin time (PT),international normalized ratio (INR),activated partial thromboplastin time (APTT),and fibrinogen (Fib) were measured,followed by a statistical analysis of all results.Results The PLT of succinylated gelatin group and hydroxyethyl starch group at intervals of 24 and 48 hours were (124.3±52.7),(78.8±16.4)×109/L and (159.0±62.8),(87.3±32.0)×109/L respectively.But in the allogeneic plasma group at intervals of 8,24,and 48 hours were (234.3±52.6),(136.0±47.4),(75.8±31.0)×109/L.The decrease were all statistically significant (P <0.05,P <0.01) when compared to pre-burn ((383.3±77.9),(382.7±65.7),(381.0±49.4)×109/L).The PLT among the three groups,at all the time points,had no statistical difference (P >0.05).Compared to pre-burn ((10.8±0.9),(11.4±0.8),(10.6±0.7) seconds),the PT of succinylated gelatin group and hydroxyethyl starch group at 24 hours were (14.5±1.5) and (16.2±1.3) seconds,whereas in the allogeneic plasma group at 8 and 24 hours the PT were

  20. Development of a microplate coagulation assay for Factor V in human plasma

    Directory of Open Access Journals (Sweden)

    Samis John A

    2011-06-01

    Full Text Available Abstract Background Factor V (FV in its activated form, FVa, is a critical regulator of thrombin generation during fibrin clot formation. There is a need of a simple, fast, and inexpensive microplate-based coagulation assay to measure the functional activity of FV in human plasma. The objective of this study was to develop a microplate-based assay that measures FV coagulation activity during clot formation in human plasma, which is currently not available. Methods The FV assay requires a kinetic microplate reader to measure the change in absorbance at 405nm during fibrin formation in human plasma. The FV assay accurately measures the time, initial rate, and extent of fibrin clot formation in human plasma. Results The FV microplate assay is simple, fast, economical, sensitive to approx 24-80pM, and multiple samples may be analyzed simultaneously. All the required materials are commercially available. Standard curves of time or initial rate of fibrin clot formation vs FV activity in the 1-stage assay (Without activation by thrombin may be used to measure FV activity in samples of human plasma. The assay was used to demonstrate that in nine patients with disseminated intravascular coagulation (DIC, the FV 1-stage, 2-stage (With activation by thrombin, and total (2-stage activity - 1-stage activity activities were decreased, on average, by approximately 54%, 44%, and 42%, respectively, from prolonged clot times when compared to normal pooled human reference plasma (NHP. The results indicate that the FV in the DIC patient plasmas supported both a delayed and slower rate of fibrin clot formation compared with NHP; however, the extent of fibrin clot formation in the DIC patients remained largely unchanged from that observed with NHP. Conclusions The FV microplate assay may be easily adapted to measure the activity of any coagulation factor using the appropriate factor-deficient plasma and clot initiating reagent. The microplate assay will find use in

  1. AI-08SUBGROUP-SPECIFIC DEREGULATION OF COAGULATION AND ANGIOGENIC GENE EXPRESSION PROFILES IN MEDULLOBLASTOMA- EVIDENCE FOR CROSS-TALK BETWEEN GROWTH FACTOR AND COAGULATION PATHWAYS

    OpenAIRE

    D'Asti, Esterina; Kool, Marcel; Pfister, Stefan; Rak, Janusz

    2014-01-01

    INTRODUCTION: Pediatric medulloblastoma (MB) is comprised of 4 distinct disease subtypes including WNT, SHH, group 3, and group 4, which co-segregate with specific clinical features and activation of distinct oncogenic pathways. Oncogenes deregulate tumour cell interactions with the vascular system including the expression, activity, and signaling properties of specific coagulation factors and their cellular receptors. The latter are often activated in aggressive cancers and involved in shapi...

  2. Levels of prolactin in relation to coagulation factors and risk of venous thrombosis. Results of a large population-based case-control study (MEGA-study).

    Science.gov (United States)

    Stuijver, Danka J F; Debeij, Jan; van Zaane, Bregje; Dekkers, Olaf M; Smit, Jan W A; Büller, Harry R; Rosendaal, Frits R; Gerdes, Victor E A; Cannegieter, Suzanne C

    2012-09-01

    The pituitary hormone prolactin is thought to influence coagulation. We aimed to study the relation between prolactin levels, coagulation factors and risk of venous thrombosis (VT). We used data from a large population based case-control study into aetiology of first VT (MEGA-study). Prolactin levels were determined in 2,068 patients with VT and 2,785 age- and sex matched control subjects. The relation between levels of coagulation factors and prolactin was studied among the controls. In addition, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated for the risk of VT for different cut-off points of prolactin levels based on percentiles determined in the controls. Restricted analysis was performed among cases in whom blood was sampled within six months after VT. We found a rise in factor VIII and von Willebrand factor with increasing levels of prolactin in the controls. An increased risk of VT was observed when blood was sampled within six months after thrombosis (OR 2.9, 95%CI 1.1-8.1) for prolactin levels above the 99th percentile (42.6 μg/l) relative to levels between the 20th to 80th percentile. When blood was sampled more than six months after VT no clear association could be observed (OR 1.3, 95%CI 0.7-2.3). In conclusion, we found a modest association between prolactin and symptomatic venous thromboembolism, particularly when blood was sampled close to the event. This may be explained by a causal relation or by prolactin being a marker of stress due to the thrombotic event.

  3. Influence of various coagulation factors on chemical composition of sera gained by centrifugation from casein gel

    Directory of Open Access Journals (Sweden)

    Jovanović Snežana T.

    2004-01-01

    Full Text Available Technological operations applied during curd processing influence syneresis and total solids content of cheese. Syneresis is not a simple physical process representing whey segregation due to curd contractions. Numerous factors can influence the process of syneresis. The aim of this work was to investigate the influence of various parameters (pH, quantity of CaCl2 added, temperature of coagulation and heat treatment on induced syneresis. Reconstituted instant skim milk (control samples and reconstituted instant skim milk heated at 87ºC for 10 min (experimental samples were coagulated at 30ºC and 35ºC, and pH of 5.8 and 6.2 with 100, 200 and 400 mg/l of CaCl2 added. According to our results, these parameters had significant influence on nitrogen content of serum as well as on the distribution of nitrogen matter from gel into sera. Due to the formation of coaggregates the best rheological properties of gel were obtained for experimental samples coagulated with 400 mg/l of CaCl2 added at pH 5.8 and temperature of 35ºC.

  4. Establishment of reference intervals for von Willebrand factor antigen and eight coagulation factors in a Korean population following the Clinical and Laboratory Standards Institute guidelines.

    Science.gov (United States)

    Jang, Ja-Hyun; Seo, Ja-Young; Bang, Sung-Hwan; Park, In-Ae; Kim, Hee-Jin; Kim, Sun-Hee

    2010-04-01

    Establishment of reference intervals for coagulation molecules is important but is costly and sometimes not feasible. Since reference intervals from manufacturers or the literature are mostly out of date or involved Western populations, the authors determined reference intervals for VWF: Ag and eight factors in a Korean population. VWF: Ag, factor VIII (FVIII), FII, FV, FVII, FIX, FX, FXI, and FXII were determined in Korean individuals visiting for routine checkup following the CLSI (Clinical and Laboratory Standards Institute) guidelines. Reagents by Diagnostica Stago were used on the STA Compact Analyzer (Diagnostica Stago). Exclusion criteria were medical history or laboratory findings that could affect the factor levels. Influence of demographic factors was analyzed. Mean +/- 2 x SD or central 95 percentile was used, as appropriate. We obtained data from 266 adults for VWF: Ag, 371 adults for FVIII, and minimum 136 adults for the rest. Reference interval for VWF was 51-176% (52-155% in blood group O and 71-186% for non-O). Reference interval for FVIII was 64-197% (55-150% in O and 77-205% in non-O). Reference interval for FII was 77-121%, FV 81-160%, FVII 68-149%, FIX 67-154%, FX 69-126%, FXI 59-138%, and FXII 48-177%. The medians of VWF: Ag, FVIII, and FIX were significantly higher in the elderly group (> or =60 years). We established local reference intervals for VWF: Ag and eight coagulation factors in a Korean population according to the CLSI guidelines. Significantly, different reference intervals were obtained in blood group O vs. non-O for VWF: Ag and FVIII. The reference intervals obtained in this study could be adopted in other clinical laboratories after appropriate validation.

  5. Effects of puerarin on blood coagulation%葛根素对凝血功能的影响

    Institute of Scientific and Technical Information of China (English)

    于晨; 范华英

    2011-01-01

    OBJECTIVE Through the study on different doses of puerarin on blood coagulation time, platelet aggregation and the role of hemorheology to investigate the effect of puerarin on coagulation function and its mechanism of action. METHODS Three different doses of oral liquid of puerarin were given respectively in normal mice, the clotting time and bleeding time were measured; after dose conversion the three different doses of oral liquid of puerarin were given in normal rats for the study onthe index of platelet aggregation hemorheology. RESULTS Different doses of puerarin group could significantly prolong the coagulation time; significantly inhibited platelet aggregation and reduce the high, medium and low shear rate whole blood viscosity. CONCLUSION These results suggest that puerarin has potent anti-coagulant. The anti-coagulant effect is related to inhibitory effect on platelet aggregation and improve hemorheology.%目的:通过研究不同剂量葛根素对凝出血时间、血小板聚集以及血流变学的作用,探讨其对凝血功能方面的影响及作用机制.方法:分别将3种不同剂量的葛根素药液灌胃给予正常小鼠,测凝血时间和出血时间;剂量转换后再将3种不同剂量的葛根素药液灌胃给予正常大鼠测定血小板聚集率和血液流变学指标.结果:不同剂量葛根素组可显著延长出、凝血时间;明显抑制血小板聚集率;能显著降低高、中、低切变率下的全血黏度.结论:葛根素有较强的抗凝血作用,其抗凝作用与其抑制血小板聚集作用和改善血流变有关.

  6. Unexpected postpartum hemorrhage due to an acquired factor VIII inhibitor.

    Science.gov (United States)

    Paidas, Michael J; Hossain, Nazli

    2014-09-01

    Unexplained postpartum hemorrhage (PPH) refractory to standard hemostatic measures should trigger a heightened clinical suspicion of an acquired bleeding disorder. When hemostatic medical interventions and surgical procedures fail to control the bleeding, then significant postoperative blood loss, debilitating morbidity, loss of fertility, and death may occur. In the setting of an autoantibody inhibitor to factor VIII (FVIII), control of life-threatening PPH and avoidance of subsequent bleeding episodes depends on a timely and accurate diagnosis, prompt hemostatic treatment and eradication of FVIII inhibitors, and appropriate long-term patient care and management. Acquired postpartum hemophilia due to a FVIII inhibitor is a rare cause of PPH; however, delayed treatment can lead to increased maternal morbidity and mortality. Acquired FVIII inhibitors also pose an emerging bleeding threat to the neonate as a result of possible transplacental transfer of FVIII autoantibodies to the fetus during the last trimester of pregnancy. The purpose of this review is to increase awareness among hematologists and obstetricians/gynecologists regarding the occurrence of FVIII neutralizing autoantibodies as a cause of PPH, and emphasize the importance of collaboration between obstetrician/gynecologists and hematology specialists to optimize the diagnostic evaluation, treatment, and long-term management of women who experience PPH due to an acquired FVIII inhibitor. PMID:24338123

  7. 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 for...

  8. Inflammation and the coagulation system in tuberculosis: Tissue Factor leads the dance.

    Science.gov (United States)

    Caccamo, Nadia; Dieli, Francesco

    2016-02-01

    Mycobacterium tuberculosis, the causative agent of tuberculosis, drives the formation of granulomas, structures in which both immune cells and the bacterial pathogen cohabit. The most abundant cells in granulomas are macrophages, which contribute as both cells with bactericidal activity and as targets for M. tuberculosis infection and proliferation during the entire course of infection. The mechanisms and factors involved in the regulation and control of macrophage microenvironment-specific polarization and plasticity are not well understood, as some granulomas are able to control bacteria growth and others fail to do so, permitting bacterial spread. In this issue of the European Journal of Immunology, Venkatasubramanian et al. [Eur. J. Immunol. 2016. 46: 464-479] show that mice lacking the tissue factor gene in myeloid cells have augmented M. tuberculosis growth and increased inflammation in the lungs. This suggests that tissue factor, an initiator of coagulation, is important for the generation of fibrin, which supports granuloma formation. This article demonstrates for the first time the involvement of tissue factor in inducing effective immunity against M. tuberculosis, and sheds new lights on the complex interplay between host inflammatory response, the coagulation system, and the control of M. tuberculosis infection. PMID:26763085

  9. Pharmacogenetic typing for oral anti-coagulant response among factor V Leiden mutation carriers

    Science.gov (United States)

    Nahar, Risha; Saxena, Renu; Deb, Roumi; Verma, Ishwar C.

    2012-01-01

    CONTEXT: Factor V Leiden mutation is the most common inherited predisposition for hypercoagulability and thereby a common genetic cause for initiation of oral anti-coagulation therapy. There is a dearth of knowledge of coumarin response profile in such thrombophilic population. AIMS: The current pilot study aims to estimate coumarin sensitivity in an Indian cohort with an inherited thrombophilia risk factor (Factor V Leiden mutation carriers) based on the observed frequency of CYP2C9 *2, *3 and VKORC1-1639G >A genotype combinations. SETTINGS AND DESIGN: A retrospective study carried out in a tertiary health care center in India. MATERIALS AND METHODS: Carriers of FVL mutation were genotyped for CYP2C9 (*2, F*3) and VKORC1 (-1639G >A) variants by PCR-RFLP technique. STATISTICAL ANALYSIS USED: Chi-square test to analyze difference in expected and observed genotype frequency. RESULTS: Sixty-one (n = 61) unrelated carriers of FVL mutation were observed in the 13 years study period. The allele frequency of CYP2C9 *2, CYP2C9 *3, and VKORC1-1639A in this cohort was 0.06, 0.11, and 0.16, respectively. Six (9.7%) individuals had two of the three variant alleles (heterozygous or homozygous), and 28 (45.9%) were heterozygous for at least one polymorphism. CONCLUSIONS: Pre-prescription genotyping for coumarin drugs, if introduced in Indians with inherited thrombophilia (in whom oral anti-coagulant therapy may be necessary), is likely to identify 9.7% (hypersensitive) subjects in whom the optimum anti-coagulation may be achieved with reduced dosages, 44.3% (normal sensitivity) who may require higher dose and also 55.6% (hyper and moderate sensitivity) subjects who are likely to experience bleeding episodes. PMID:23716941

  10. Effects of Xuezhikang Capsule(血脂康胶囊) on Blood Lipids,Platelet Activation and Coagulation-Fibrinolysis Activity in Patients with Hyperlipidemia

    Institute of Scientific and Technical Information of China (English)

    刘志高; 余细勇

    2004-01-01

    Objective: To investigate the effects of Xuezhikang capsule (XZK, 血脂康胶囊) on blood lipids level, platelet activation and coagulation-fibrinolysis activity in patients with hyerlipidemia. Methods:Seventy-six patients of hyperlipidemia were randomly divided into two groups, the XZK group (n = 38) treated with XZK 600mg, taken two times per day and the Simvastatin (SIM) group (n = 38) treated with SIM 20mg per day, with the treatment lasting 8 weeks for both groups. Levels of fasting serum lipids, including total cholesterol (TC), triglyceride (TG), high and low density l ipoprotein cholesterol (HDL-C and LDL-C),plasma GMP-140, fibrinogen (FIB), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAl-) and prothrombin time (PT) were all measured before and 8 weeks after treatment. Data were compared before and after treatment and also compared with those measured in 20 healthy subjects of control. Results: Before treantment the levels of TC, TG and LDL-C were obviously higher and HDL-C level was significantly lower in hyperlipidemia patients than those in healthy subjects ( P<0.05 or P<0.01). After 4-8 weeks of XZK treatment, the levels of TC, TG, LDL-C and FIB and activities of GMP-140 and PAl-1 were obviously lowered (P<0.05 or P<0.01). But in the SIM group there was no obvious change in FIB (P>0.05), instead it showed obvious increase of HDL-C and decrease of TC and LDL-C after treatment ( P<0.05 or P<0.01). Conclusion: XZK could inhibit platelet activity and improve coagulation-fibrinolysis function, besides its lipids lowering effect.

  11. Behavior of optical properties of coagulated blood sample at 633 nm wavelength

    Science.gov (United States)

    Morales Cruzado, Beatriz; Vázquez y Montiel, Sergio; Delgado Atencio, José Alberto

    2011-03-01

    Determination of tissue optical parameters is fundamental for application of light in either diagnostics or therapeutical procedures. However, in samples of biological tissue in vitro, the optical properties are modified by cellular death or cellular agglomeration that can not be avoided. This phenomena change the propagation of light within the biological sample. Optical properties of human blood tissue were investigated in vitro at 633 nm using an optical setup that includes a double integrating sphere system. We measure the diffuse transmittance and diffuse reflectance of the blood sample and compare these physical properties with those obtained by Monte Carlo Multi-Layered (MCML). The extraction of the optical parameters: absorption coefficient μa, scattering coefficient μs and anisotropic factor g from the measurements were carried out using a Genetic Algorithm, in which the search procedure is based in the evolution of a population due to selection of the best individual, evaluated by a function that compares the diffuse transmittance and diffuse reflectance of those individuals with the experimental ones. The algorithm converges rapidly to the best individual, extracting the optical parameters of the sample. We compare our results with those obtained by using other retrieve procedures. We found that the scattering coefficient and the anisotropic factor change dramatically due to the formation of clusters.

  12. Effects of platelet inhibitors on propyl gallate-induced platelet aggregation, protein tyrosine phosphorylation, and platelet factor 3 activation.

    Science.gov (United States)

    Xiao, Hongyan; Kovics, Richard; Jackson, Van; Remick, Daniel G

    2004-04-01

    Propyl gallate (PG) is a platelet agonist characterized by inducing platelet aggregation, protein tyrosine phosphorylation, and platelet factor 3 activity. The mechanisms of platelet activation following PG stimulation were examined by pre-incubating platelets with well-defined platelet inhibitors using platelet aggregation, protein tyrosine phosphorylation, activated plasma clotting time, and annexin V binding by flow cytometry. PG-induced platelet aggregation and tyrosine phosphorylation of multiple proteins were substantially abolished by aspirin, apyrase, and abciximab (c7E3), suggesting that PG is associated with activation of platelet cyclooxygenase 1, adenosine phosphate receptors, and glycoprotein IIb/IIIa, respectively. The phosphorylation of the cytoskeletal enzyme pp60(c-src) increased following PG stimulation, but was blunted by pre-incubation of platelets with aspirin, apyrase, and c7E3, suggesting that tyrosine kinase is important for the signal transduction of platelet aggregation. Propyl gallate also activates platelet factor 3 by decreasing the platelet coagulation time and increasing platelet annexin V binding. Platelet incubation with aspirin, apyrase, and c7E3 did not alter PG-induced platelet coagulation and annexin V binding. The results suggest that platelet factor 3 activation and membrane phosphotidylserine expression were not involved with activation of platelet cyclooxygenase, adenosine phosphate receptors, and glycoprotein IIb/IIIa. PG is unique in its ability to stimulate platelet aggregation and coagulation simultaneously, and platelet inhibitors in this study affect only platelet aggregation but not platelet coagulation. PMID:15060414

  13. 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.

  14. Hydatid cyst surgery complicated by hemorrhage resistant to activated recombinant factor VII, in a hemophiliac A patient with an inhibitor.

    Science.gov (United States)

    Nabil, Saad; Bentalha, Aziza; Jaiteh, Lamine; El Khorassani, Mohammed; El Koraichi, Alae; El Kettani, Salma E-C

    2016-09-01

    Factor VII is a new coagulation factor replacement therapy. It has permitted the practice of invasive procedures which were up until recently associated with a huge risk of bleeding in patients with hemophilia with inhibitors. Our case illustrates factor replacement therapy failure in a 13-year-old child operated on for hepatic cysts associated with a pelvic cyst. Major bleeding occurred postoperatively requiring several transfusions, an increase in dosage of factor VII, and administration of a heavy dose of factor VIII as a last resort. This case highlights the possibility of failure of factor replacement therapies constituting a life-threatening situation in which alternatives are few. PMID:26761579

  15. 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.

  16. Virus host protein interaction network analysis reveals that the HEV ORF3 protein may interrupt the blood coagulation process.

    Directory of Open Access Journals (Sweden)

    Yansheng Geng

    Full Text Available Hepatitis E virus (HEV is endemic worldwide and a major cause of acute liver disease in developing countries. However, the molecular mechanisms of liver pathology and clinical disease are not well understood for HEV infection. Open reading frame 3 (ORF3 of HEV encodes a small phosphoprotein, which is assumed to be involved in liver pathology and clinical disease. In this study, the interactions between the HEV ORF3 protein and human proteins were investigated using a stringent, high-throughput yeast two-hybrid (Y2H analysis. Thirty two proteins were shown to interact with genotype 1 ORF3, 28 of which have not been reported previously. These novel interactions were evaluated by coimmunoprecipitation of protein complexes from transfected cells. We found also that the ORF3 proteins of genotype 4 and rabbit HEV interacted with all of the human proteins identified by the genotype 1 ORF3 protein. However, the putative ORF3 protein derived from avian HEV did not interact with the majority of these human proteins. The identified proteins were used to infer an overall interaction map linking the ORF3 protein with components of the host cellular networks. Analysis of this interaction map, based on functional annotation with the Gene Ontology features and KEGG pathways, revealed an enrichment of host proteins involved in complement coagulation, cellular iron ion homeostasis and oxidative stress. Additional canonical pathway analysis highlighted the enriched biological pathways relevant to blood coagulation and hemostasis. Consideration of the clinical manifestations of hepatitis E reported previously and the results of biological analysis from this study suggests that the ORF3 protein is likely to lead to an imbalance of coagulation and fibrinolysis by interacting with host proteins and triggering the corresponding pathological processes. These results suggest critical approaches to further study of the pathogenesis of the HEV ORF3 protein.

  17. Dysinosin A: a novel inhibitor of Factor VIIa and thrombin from a new genus and species of Australian sponge of the family Dysideidae.

    Science.gov (United States)

    Carroll, Anthony R; Pierens, Gregory K; Fechner, Greg; De Almeida Leone, Priscila; Ngo, Anna; Simpson, Moana; Hyde, Edward; Hooper, John N A; Boström, Stig-Lennart; Musil, Djordje; Quinn, Ronald J

    2002-11-13

    A new marine natural product dysinosin A 1 has been isolated from a new genus and species of sponge of the family Dysideidae found near Lizard Island, North Queensland, Australia. Dysinosin A is a potent inhibitor of the blood coagulation cascade factor VIIa and an inhibitor of the serine protease thrombin. Among the distinctive features of dysinosin A are the presence of a 5,6-dihydroxy-octahydroindole-2-carboxylic acid, 3-amino-ethyl 1-N-amidino-Delta-3-pyrroline, a sulfated glyceric acid, and d-leucine, assembled through three peptidic linkages. Dysinosin A inhibited factor VIIa at a Ki of 108 nM and thrombin at a Ki of 452 nM. The identification of the 1-N-amidino-Delta-3-pyrroline and 5,6-dihydroxy-octahydroindole-2-carboxylic acid as P1 and P2 moieties respectively, should pave the way for the design and synthesis of new structure-based inhibitors. PMID:12418859

  18. Polyphosphate, Platelets, and Coagulation

    OpenAIRE

    Travers, Richard J.; Smith, Stephanie A.; Morrissey, James H

    2015-01-01

    While we have understood the basic outline of the enzymes and reactions that make up the traditional blood coagulation cascade for many years, recently our appreciation of the complexity of these interactions has greatly increased. This has resulted in unofficial “revisions” of the coagulation cascade to include new amplification pathways and connections between the standard coagulation cascade enzymes, as well as the identification of extensive connections between the immune system and the c...

  19. Disseminated intravascular coagulation.

    Science.gov (United States)

    Gando, Satoshi; Levi, Marcel; Toh, Cheng-Hock

    2016-01-01

    Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by widespread intravascular activation of coagulation that can be caused by infectious insults (such as sepsis) and non-infectious insults (such as trauma). The main pathophysiological mechanisms of DIC are inflammatory cytokine-initiated activation of tissue factor-dependent coagulation, insufficient control of anticoagulant pathways and plasminogen activator inhibitor 1-mediated suppression of fibrinolysis. Together, these changes give rise to endothelial dysfunction and microvascular thrombosis, which can cause organ dysfunction and seriously affect patient prognosis. Recent observations have pointed to an important role for extracellular DNA and DNA-binding proteins, such as histones, in the pathogenesis of DIC. The International Society on Thrombosis and Haemostasis (ISTH) established a DIC diagnostic scoring system consisting of global haemostatic test parameters. This scoring system has now been well validated in diverse clinical settings. The theoretical cornerstone of DIC management is the specific and vigorous treatment of the underlying conditions, and DIC should be simultaneously managed to improve patient outcomes. The ISTH guidance for the treatment of DIC recommends treatment strategies that are based on current evidence. In this Primer, we provide an updated overview of the pathophysiology, diagnosis and management of DIC and discuss the future directions of basic and clinical research in this field. PMID:27250996

  20. 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.

  1. [Incidental finding of pathological coagulation parameters].

    Science.gov (United States)

    Luxembourg, B; Lindhoff-Last, E

    2014-10-01

    Pathological coagulation parameters may reflect life-threatening hemorrhagic or thromboembolic diseases but may also be a laboratory result without any clinical significance, result from in vitro phenomena or preanalytical errors. This article gives an overview of potential pitfalls in coagulation diagnostics, lists the differential diagnoses of pathological coagulation parameters and describes further steps in the diagnostic approach to clarify pathological results. The focus lies on coagulation parameters that are frequently determined in routine clinical investigations, e.g. platelet count, prothrombin time, activated partial thromboplastin time (aPTT) and fibrinogen. Besides heparin, fondaparinux, danaparoid, and vitamin K antagonists, direct factor Xa inhibitors and direct thrombin inhibitors are nowadays available for therapeutic anticoagulation. This article gives an overview of the influence of anticoagulants on coagulation parameters which depends on the dose, the time of the last administration, as well as the method used for the determination of coagulation parameters. Moreover, common reasons for elevation of the fibrin degradation product D-dimer are presented. The clinical utility of D-dimer assays is limited by their poor specificity. Elevated D-dimer concentrations can be found in various diseases and also under normal physiological circumstances (e.g. in the elderly). Thus, the most useful clinical application of D-dimer is evidence of normal values to essentially rule out venous thromboembolism. PMID:25190093

  2. International Normalized Ratio (INR), coagulation factor activities and calibrated automated thrombin generation - influence of 24 h storage at ambient temperature

    DEFF Research Database (Denmark)

    Christensen, T D; Jensen, C; Larsen, T B;

    2010-01-01

    clotting activity of coagulation factors II, VII, IX, and X as well as CAT generation was recorded after 0 and 24 h respectively. Statistical analyses included Bland-Altman plot, 95% limits of agreement, and a variability test using a mixed effect model. The level of INR remained statistically unchanged......International Normalized Ratio (INR) measurements are used to monitor oral anticoagulation therapy with coumarins. Single coagulation factor activities and calibrated automated thrombin (CAT) generation are considered as more advanced methods for evaluating overall haemostatic capacity. The aims...

  3. ARTEMISIA DRACUNCULUS, PUNICA GRANATUM AND BERBERIS VULGARIS INHIBITORY EFFECTS ON PLATELET ADHESION AND COAGULATION FACTORS IN RATS

    Directory of Open Access Journals (Sweden)

    Dr. Razieh Yazdanparast et al

    2012-10-01

    Full Text Available Excessive platelet activity is one of the most important factors responsible for the incidence of cardiovascular diseases and, also, play important role in coagulation cascade. In this study, the comparative effects of methanol extracts of three herbs on adhesion of the activated platelets to fibrinogen coated plates and clotting factors were investigated. Artemisia dracunculus, Punica granatum and Brberis vulgaris are used as blood anti-coagulatory plants in Iranian folk medicine. Platelets were prepared and incubated with different concentration of the test samples (50-200 μg/ml for 60 min. The treated and un-treated platelets were then activated with thrombin (0.25U/ml and their adhesions to fibrinogen coated plates were investigated. Based on obtained data, the methanol extract of Artemisia dracunculus, Brberis vulgaris and Punica granatum at a concentration of 200 μg /ml reduced platelet adhesion to coated wells by 35%, 25% and 20%, respectively. In addition, the effects of the crude extracts of each plant on atherogenic lipoproteins were also examined. The results indicated that the LDL and cholesterol concentration were dramatically reduced by 56% and 36%, respectively, by B. vulgaris. This result provided the scientific basis for the traditional use of A.dracunculus and B. vulgaris in treatment of cardiovascular related disorders.

  4. Structure-guided creation of AcAP5-derived and platelet targeted factor Xa inhibitors.

    Science.gov (United States)

    Zhu, Yuanjun; Lin, Yuan; Liu, Aihua; Shui, Mengyang; Li, Ruyi; Liu, Xiaoyan; Hu, Wenhui; Wang, Yinye

    2015-06-15

    Anticoagulants and anti-platelet agents are simultaneously administrated in clinical practice (i.e. percutaneous coronary intervention), which cause significant risk of systemic bleeding. Targeted delivery of anticoagulants to the activated platelets at sites of vascular injuries may condense the site-specific anticoagulant effect and reduce the hemorrhage side effects in uninjured vessels. To this end, we prepared three ancylostoma caninum anticoagulant peptide 5 (AcAP5) variants NR1, NR2 and NR3 engineered with a platelet-binding Arg-Gly-Asp (RGD) motif and evaluated their anti-Factor Xa (FXa) and platelet-binding effects. These RGD-containing AcAP5 variants were capable of interacting with platelet receptor αIIbβ3 as shown in computational analysis. All variants, especially NR2 and NR3, retained entirely the anti-FXa function of parent AcAP5. Moreover, they prevented the formation of occlusive thrombi in rat carotid artery injury model, suggesting that they inhibit platelet aggregation in vivo. Further functional investigation of NR3 demonstrated that NR3 inhibited platelet aggregation in vitro and FXa activity in vivo, and prolonged the coagulation time, all in a dose-dependent manner. Through flow cytometry assay, we confirmed the binding of NR3 to αIIbβ3 receptor. In mouse model of carotid artery endothelium injury, NR3-treated mice showed less tail bleeding time than AcAP5-treated mice, and aspirin plus NR3 treatment exhibited moderate reduction of blood loss compared with aspirin plus AcAP5 treatment. These results indicate the feasibility to engineer a novel FXa inhibitor specifically targeting the activated platelets, which centralizes its anticoagulation efficacy in the injured vascular endothelium and reduces the risk of systemic bleeding. PMID:25887920

  5. Development of acquired factor V inhibitor after treatment with ceftazidime: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Cui QY

    2015-04-01

    Full Text Available Qing-ya Cui,1 Hong-shi Shen,1 Tian-qin Wu,1 Hai-fei Chen,1 Zi-qiang Yu,2 Zhao-yue Wang2 1Department of Hematology, PLA 100th Hospital, 2Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China Abstract: We report the case of a 59-year-old Chinese man who showed an asymptomatic coagulation factor V deficiency pattern after second intravenous treatment with ceftazidime. Normal pooled plasma failed to correct the abnormalities in a mixing test, and the presence of factor V inhibitor was confirmed by the Bethesda method. The coagulopathy was not corrected by transfusion of fresh frozen plasma and prothrombin complex concentrate, but rather by treatment with prednisone and withdrawal of dubious drugs. The findings reported here should prompt clinicians to watch for drug-induced coagulation factor deficiency. Keywords: acquired factor V deficiency, coagulopathy, prednisone

  6. Coagulation and complement system in critically ill patients.

    Science.gov (United States)

    Helling, H; Stephan, B; Pindur, G

    2015-01-01

    Activation of coagulation and inflammatory response including the complement system play a major role in the pathogenesis of critical illness. However, only limited data are available addressing the relationship of both pathways and its assessment of a predictive value for the clinical outcome in intense care medicine. Therefore, parameters of the coagulation and complement system were studied in patients with septicaemia and multiple trauma regarded as being exemplary for critical illness. 34 patients (mean age: 51.38 years (±16.57), 15 females, 19 males) were investigated at day 1 of admittance to the intensive care unit (ICU). Leukocytes, complement factors C3a and C5a were significantly (p complement system as part of the inflammatory response is a significant mechanism in septicaemia, whereas loss and consumption of blood components including parts of the coagulation and complement system is more characteristic for multiple trauma. Protein C in case of severe reduction might be of special concern for surviving in sepsis. Activation of haemostasis was occurring in both diseases, however, overt DIC was not confirmed in this study to be a leading mechanism in critically ill patients. MOF score, lactate, C1-inhibitor and prothrombin time have been the only statistically significant predictors for lethal outcome suggesting that organ function, microcirculation, haemostasis and inflammatory response are essential elements of the pathomechanism and clinical course of diseases among critically ill patients.

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

    Directory of Open Access Journals (Sweden)

    Rolf eBurghaus

    2014-11-01

    Full Text Available 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.

  8. The new factor Xa inhibitor: Apixaban

    Directory of Open Access Journals (Sweden)

    Sangeeta Bhanwra

    2014-01-01

    Full Text Available Cardiovascular diseases are still the most important cause of morbidity and mortality worldwide and anti-thrombotic treatment is widely used as a result. The currently used drugs include heparin and its derivatives, vitamin K antagonists, though efficacious, have their own set of limitations like unpredictable pharmacokinetic profile, parenteral route (with heparin and its derivatives only, narrow therapeutic window, and constant laboratory monitoring for their efficacy and safety. This lead to the development of novel factor Xa inhibitors which could be given orally, have predictable dose response relationship and are associated with lesser hemorrhagic complications. They include rivaroxaban, apixaban, and edoxaban among others. Apixaban has currently been approved for use in patients undergoing total knee or hip replacement surgery and to prevent stroke in patients with atrial fibrillation. Many trials are ongoing for apixaban to firmly establish its place in future, among the anti-thrombotic drugs.

  9. Advances on Mechanisms of Coagulation with Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yanhua LI

    2013-12-01

    Full Text Available Recently, researchers have been increasingly finding coagulation disorders are commonly the first sign of malignancy. It has now been established that cancer development leads to an increased risk of thrombosis, and conversely, excessive activation of blood coagulation profoundly influences cancer progression. In patients with lung cancer, a sustained stimulation of blood coagulation takes place. Cancer cells trigger coagulation through expression of tissue factor, and affect coagulation through expression of thrombin, release of microparticles that augment coagulation and so on. Coagulation also facilitates tumour progression through release of platelet granule contents, inhibition of natural killer cells and recruitment of macrophages. Non-small cell lung cancer (NSCLC accounts for about 80%-85% of all lung malignancies. In the present review, we summarized the newly updated data about the physiopathological mechanisms of various components of the clotting system in different stages of carcinogenesis in NSCLC.

  10. Protein trans-splicing based dual-vector delivery of the coagulation factor Ⅷ gene

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A dual-vector system was explored for the delivery of the coagulation factor VIII gene,using intein-mediated protein trans-splicing as a means to produce intact functional factor VIII post-translationally.A pair of eukaryotic expression vectors,expressing Ssp DnaB intein-fused heavy and light chain genes of B-domain deleted factor VIII (BDD-FVIII),was constructed.With transient co-transfection of the two vectors into 293 and COS-7 cells,the culture supernatants contained (137±23) and (109±22) ng mL–1 spliced BDD-FVIII antigen with an activity of (1.05±0.16) and (0.79±0.23) IU mL–1 for 293 and COS-7 cells,respectively.The spliced BDD-FVIII was also detected in supernatants from a mixture of cells transfected with inteinfused heavy and light chain genes.The spliced BDD-FVIII protein bands from cell lysates were visualized by Western blotting.The data demonstrated that intein could be used to transfer the split factor VIII gene and provided valuable information on factor VIII gene delivery by dual-adeno-associated virus in hemophilia A gene therapy.

  11. Long-Acting Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Children

    Science.gov (United States)

    Chambost, Hervé; Male, Christoph; Lambert, Thierry; Halimeh, Susan; Chernova, Tatiana; Mancuso, Maria Elisa; Curtin, Julie; Voigt, Christine; Li, Yanyan; Jacobs, Iris; Santagostino, Elena

    2016-01-01

    Summary A global phase 3 study evaluated the pharmacokinetics, efficacy and safety of a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 27 previously treated male children (1–11 years) with severe and moderately severe haemophilia B (factor IX [FIX] activity ≤2 IU/dl). All patients received routine prophylaxis once every seven days for up to 77 weeks, and treated any bleeding episodes on-demand. The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment. The median (Q1, Q3) annualised spontaneous bleeding rate was 0.00 (0.00, 0.91) and was similar between the <6 years and ≥6 years age groups, with a weekly median prophylactic dose of 46 IU/kg. In addition, patients maintained a median trough level of 13.4 IU/dl FIX activity on weekly prophylaxis. Overall, 97.2% of bleeding episodes were successfully treated with one or two injections of rIX-FP (95% CI: 92% to 99%), 88.7% with one injection, and 96% of the treatments were rated effective (excellent or good) by the Investigator. No patient developed FIX inhibitors and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in children with haemophilia B with weekly prophylaxis. Routine prophylaxis with rIX-FP at treatment intervals of up to 14 days are currently being investigated in children with severe and moderately severe haemophilia B. Clinicaltrials.gov (NCT01662531) PMID:27583313

  12. 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.

  13. Effects on fibrinogen, fibrin, and blood coagulation of proteolytic extracts from fruits of Pseudananas macrodontes, Bromelia balansae, and B. hieronymi (Bromeliaceae) in comparison with bromelain.

    Science.gov (United States)

    Errasti, María E; Prospitti, Anabela; Viana, Carolina A; Gonzalez, Mariana M; Ramos, Márcio V; Rotelli, Alejandra E; Caffini, Néstor O

    2016-06-01

    Extracts rich in cysteine proteases obtained from fruits of Pseudananas macrodontes (Pm), Bromelia balansae (Bb), and B. hieronymi (Bh) have previously shown an anti-inflammatory effect on animal models. Given the close relationship between hemostasis and inflammation, it is attractive to investigate therapeutic agents capable of modulating both systems. The aim of this work was to study the effect of Pm, Bb, and Bh on fibrin(ogen) and blood coagulation compared with stem bromelain (Bro). Action on fibrinogen was electrophoretically and spectrophotometrically evaluated, fibrinolytic activity was measured both electrophoretically and by the fibrin plate assay, and the effect on blood coagulation was studied by conventional coagulation tests (PT and APPT). All extracts showed the same proteolytic preference for fibrinogen subunits, that is Aα > Bβ, whereas γ was partially hydrolyzed by 100-fold concentration increase. Unlike Bro, cysteine proteases of Pm, Bb, and Bh increased absorbance at 540 nm of fibrinogen solution, suggesting thrombin-like activity, which was time-dependent and reached maximum values at lower concentration. All extracts showed the same proteolytic preference for fibrin subunits; however Pm, Bb, and Bh showed lower fibrinolytic activity than Bro at the assayed concentrations. Although Bb acted only as anticoagulant, Pm, Bh, and unexpectedly Bro showed dual action on blood coagulation: at low concentration showed procoagulant effect and at high concentration anticoagulant effect. Results reveal new plant species as potential sources of pharmacological agents for the treatment of a wide range of hemostatic disorders as well as to wound healing.

  14. Role of Coagulation Factor Ⅶ in Pathogenesis of Ischemic Heart Disease

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To study the variation and significance of plasma coagulation factor Ⅶ (FⅦ) in differ ent kinds of ischemia heart disease (IHD) and examine its relation with plasma lipid and gene polymorphism. FⅦa was determined with one stage clotting assay by using a recombinant soluble tissue factor (rsTF). FⅦc was measured with one stage clotting assay. FⅦag was quantified with an enzyme-linked immunosorbent assay (ELISA). Polymorphism was analyzed with PCR-urea-polyacrylamide gel electrophoresis. Our results showed that FⅦa in stable angina (SA),unstable angina (UA), obsolete and acute myocardial infraction (OMI, AMI) patients was higher than those of normal group with the differences being significant within any two groups. FⅦag in UA, OMI and AMI was higher than those in SA and normal groups. There were positive correlations between FⅦa and serum triglycerides, FⅦa and FⅦc, FⅦc and FⅦag. FⅦ-323 0/10 bp polymorphism analysis was performed in 60 patients and 0/10 bp polymorphism was found in 5 cases. FⅦc and FⅦag were much lower in cases of 0/10 bp groups than those in cases of 0/0 bp groups. It is concluded that there was activation of extrinsic coagulation pathway in every kind of IHD to different extent. FⅦa was the risk factor in the development of IHD, and more sensitive in reflecting the severity of cardiovacutar disease than FⅦc or FⅦag. FⅦa was higher in OMI, which may be one of the risk factors of re-infraction. Serum triglyceride may indirectly lead to the development of IHD by increasing the level of FⅦa. FⅦ-323 0/10 bp polymorphism was present in Chinese patients with IHD and it was correlated with the level of FⅦc, FⅦag in plasma. 10 bp allelomorphic gene was a protective factor against thrombogenesis.

  15. Dynamically monitoring tissue factor and tissue factor pathway inhibitor following secondary brain injury

    Institute of Scientific and Technical Information of China (English)

    吴雪海; 施小燕; 干建新; 卢兴国; 江观玉; 周君富

    2003-01-01

    Objective: To study the altering rule of coagulation function at molecular level in patients with secondary brain injury (SBI).Methods: Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were studied in 32 patients 1, 2, 3 and 7 days after craniocerebral injury. Repeated cranial CT scans and platelet counts were made simultaneously. Same measurements were done in 30 normal adults except CT scan.Results: No obvious difference was found in age, sex and platelet count between the injured and the normal groups. TFPI/TF decreased markedly in the first week after injury in patients with SBI, but only decreased on the 7th day in the patients without obvious SBI. For the patients who developed delayed intracranial hematoma (DIH) or hematoma enlargement, TF rose only 1 and 2 days after injury, but TFPI had a tendency to rise again after a fall on the 3rd day. For those patients who developed no DIH, TF rose all the time within the 1st week.Conclusions: Decrease of TFPI/TF for a long time, especially within 3 days after injury, may be one of the most important reasons for SBI. High expression of TF for a relative short time and increase of TFPI after a fall within 3 days may be one of the important reasons for DIH or hematoma enlargement.

  16. 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

    blood cell count (4.80 ± 0.33 to 4.64 ± 0.37 × 10(12) cells l(-1), P < 0.05) indicating that 218 ± 173 ml fluid was recruited to the circulation. Withdrawing 450 ml blood reduced the time until initial fibrin formation (R: 6.5 ± 0.9 to 5.1 ± 1.0 min, P < 0.01), whereas the rate of clot formation...

  17. Effect of hyperbilirubunemia on coagulation system of blood in patients with obstructive jaundice

    OpenAIRE

    Sarkisian Z.O.; Tolstokorov A.S.

    2012-01-01

    Objective of the study: determination of the degree of influence of bilirubin in the blood during obstructive jaundice, on blood clotting. Methods. A retrospective study of case histories of patients with obstructive jaundice who have been treated at the Regional Hospital of Saratov in the period from 2000 to 2010. Results. The results confirm the assumption that the causes of bleeding in obstructive jaundice is hepatic failure. Conclusion. Absence of bile in the small intestine in obstructiv...

  18. Effects on coagulation and fibrinolysis induced by influenza in mice with a reduced capacity to generate activated protein C and a deficiency in plasminogen activator inhibitor type 1.

    Science.gov (United States)

    Keller, Tymen T; van der Sluijs, Koen F; de Kruif, Martijn D; Gerdes, Victor E A; Meijers, Joost C M; Florquin, Sandrine; van der Poll, Tom; van Gorp, Eric C M; Brandjes, Dees P M; Büller, Harry R; Levi, Marcel

    2006-11-24

    Influenza infections increase the risk of diseases associated with a prothrombotic state, such as venous thrombosis and atherothrombotic diseases. However, it is unclear whether influenza leads to a prothrombotic state in vivo. To determine whether influenza activates coagulation, we measured coagulation and fibrinolysis in influenza-infected C57BL/6 mice. We found that influenza increased thrombin generation, fibrin deposition, and fibrinolysis. In addition, we used various anti- and prothrombotic models to study pathways involved in the influenza-induced prothrombotic state. A reduced capacity to generate activated protein C in TM(pro/pro) mice increased thrombin generation and fibrinolysis, whereas treatment with heparin decreased thrombin generation in influenza-infected C57Bl/6 mice. Thrombin generation was not changed in hyperfibrinolytic mice, deficient in plasminogen activator inhibitor type-1 (PAI-1(-/-)); however, increased fibrin degradation was seen. Treatment with tranexamic acid reduced fibrinolysis, but thrombin generation was unchanged. We conclude that influenza infection generates thrombin, increased by reduced levels of protein C and decreased by heparin. The fibrinolytic system appears not to be important for thrombin generation. These findings suggest that influenza leads to a prothrombotic state by coagulation activation. Heparin treatment reduces the influenza induced prothrombotic state. PMID:17068293

  19. Ovarian cancer, the coagulation pathway, and inflammation.

    Science.gov (United States)

    Wang, Xipeng; Wang, Ena; Kavanagh, John J; Freedman, Ralph S

    2005-06-21

    Epithelial ovarian cancer (EOC) represents the most frequent cause of death in the United States from a cancer involving the female genital tract. Contributing to the overall poor outcome in EOC patients, are the metastases to the peritoneum and stroma that are common in this cancer. In one study, cDNA microarray analysis was performed on fresh tissue to profile gene expression in patients with EOC. This study showed a number of genes with significantly altered expression in the pelvic peritoneum and stroma, and in the vicinity of EOC implants. These genes included those encoding coagulation factors and regulatory proteins in the coagulation cascade and genes encoding proteins associated with inflammatory responses. In addition to promoting the formation of blood clots, coagulation factors exhibit many other biologic functions as well as tumorigenic functions, the later including tumor cell proliferation, angiogenesis, invasion, and metastasis. Coagulation pathway proteins involved in tumorigenesis consist of factor II (thrombin), thrombin receptor (protease-activated receptors), factor III (tissue factor), factor VII, factor X and factor I (fibrinogen), and fibrin and factor XIII. In a recent study we conducted, we found that factor XII, factor XI, and several coagulation regulatory proteins, including heparin cofactor-II and epithelial protein C receptor (EPCR), were also upregulated in the peritoneum of EOC. In this review, we summarize evidence in support of a role for these factors in promoting tumor cell progression and the formation of ascites. We also discuss the different roles of coagulation factor pathways in the tumor and peritumoral microenvironments as they relate to angiogenesis, proliferation, invasion, and metastasis. Since inflammatory responses are another characteristic of the peritoneum in EOC, we also discuss the linkage between the coagulation cascade and the cytokines/chemokines involved in inflammation. Interleukin-8, which is considered an

  20. Ovarian cancer, the coagulation pathway, and inflammation

    Directory of Open Access Journals (Sweden)

    Kavanagh John J

    2005-06-01

    Full Text Available Abstract Epithelial ovarian cancer (EOC represents the most frequent cause of death in the United States from a cancer involving the female genital tract. Contributing to the overall poor outcome in EOC patients, are the metastases to the peritoneum and stroma that are common in this cancer. In one study, cDNA microarray analysis was performed on fresh tissue to profile gene expression in patients with EOC. This study showed a number of genes with significantly altered expression in the pelvic peritoneum and stroma, and in the vicinity of EOC implants. These genes included those encoding coagulation factors and regulatory proteins in the coagulation cascade and genes encoding proteins associated with inflammatory responses. In addition to promoting the formation of blood clots, coagulation factors exhibit many other biologic functions as well as tumorigenic functions, the later including tumor cell proliferation, angiogenesis, invasion, and metastasis. Coagulation pathway proteins involved in tumorigenesis consist of factor II (thrombin, thrombin receptor (protease-activated receptors, factor III (tissue factor, factor VII, factor X and factor I (fibrinogen, and fibrin and factor XIII. In a recent study we conducted, we found that factor XII, factor XI, and several coagulation regulatory proteins, including heparin cofactor-II and epithelial protein C receptor (EPCR, were also upregulated in the peritoneum of EOC. In this review, we summarize evidence in support of a role for these factors in promoting tumor cell progression and the formation of ascites. We also discuss the different roles of coagulation factor pathways in the tumor and peritumoral microenvironments as they relate to angiogenesis, proliferation, invasion, and metastasis. . Since inflammatory responses are another characteristic of the peritoneum in EOC, we also discuss the linkage between the coagulation cascade and the cytokines/chemokines involved in inflammation. Interleukin

  1. Rethinking events in the haemostatic process: role of factor V and TFPI.

    Science.gov (United States)

    Camire, R M

    2016-07-01

    Regulatory mechanisms responsible for limiting blood clot formation are critical for maintaining normal haemostasis. Dysregulation can lead to bleeding (e.g. haemophilia) or thrombosis. New findings showing that tissue factor pathway inhibitor-alpha (TFPIα) binds coagulation factor V(a) and inhibits prothrombinase assembly highlights that our understanding of the initiation of coagulation is evolving. Work over the past decade on the biochemistry of FV activation has laid the groundwork for deciphering the mechanistic bases that may underpin how TFPIα mediates these anticoagulant effects. Collectively, these new findings are re-shaping our thinking about how coagulation is initiated at the site of injury. These ideas could have important clinical implications and help identify new ways to bias the coagulation response for the treatment of haemophilia and other disorders of the haemostatic process. PMID:27405668

  2. Potentiation of thrombin generation in hemophilia A plasma by coagulation factor VIII and characterization of antibody-specific inhibition.

    Directory of Open Access Journals (Sweden)

    Bhavya S Doshi

    Full Text Available Development of inhibitory antibodies to coagulation factor VIII (fVIII is the primary obstacle to the treatment of hemophilia A in the developed world. This adverse reaction occurs in 20-30% of persons with severe hemophilia A treated with fVIII-replacement products and is characterized by the development of a humoral and neutralizing immune response to fVIII. Patients with inhibitory anti-fVIII antibodies are treated with bypassing agents including recombinant factor VIIa (rfVIIa. However, some patients display poor hemostatic response to bypass therapy and improved treatment options are needed. Recently, we demonstrated that fVIII inhibitors display widely variable kinetics of inhibition that correlate with their respective target epitopes. Thus, it was hypothesized that for antibodies that display slow rates of inhibition, supplementation of rfVIIa with fVIII would result in improved thrombin generation and be predictive of clinical responses to this novel treatment regimen. In order to test this hypothesis, 10 murine monoclonal antibodies (MAbs with non-overlapping epitopes spanning fVIII, differential inhibition titers, and inhibition kinetics were studied using a thrombin generation assay. Of the 3 MAbs with high inhibitory titers, only the one with fast and complete (classically defined as "type I" kinetics displayed significant inhibition of thrombin generation with no improvement upon supplementation of rfVIIa with fVIII. The other two MAbs that displayed incomplete (classically defined as "type II" inhibition did not suppress the potentiation of thrombin generation by fVIII. All antibodies that did not completely inhibit fVIII activity demonstrated potentiation of thrombin generation by the addition of fVIII as compared to rfVIIa alone. In conclusion, fVIII alone or in combination with rfVIIa corrects the thrombin generation defect produced by the majority of anti-fVIII MAbs better than single agent rfVIIa. Therefore, combined f

  3. Inhibitors

    Science.gov (United States)

    ... wrong place in the body. Immune Tolerance Induction (ITI) Therapy: The goal of ITI therapy is to stop the inhibitor reaction from ... body to accept clotting factor concentrate treatments. With ITI therapy, people receive large amounts of clotting factor ...

  4. Levels of prolactin in relation to coagulation factors and risk of venous thrombosis. Results of a large population-based case-control study (MEGA-study)

    NARCIS (Netherlands)

    Stuijver, D.J.; Debeij, J.; Zaane, B. van; Dekkers, O.M.; Smit, J.W.A.; Buller, H.R.; Rosendaal, F.R.; Gerdes, V.E.; Cannegieter, S.C.

    2012-01-01

    The pituitary hormone prolactin is thought to influence coagulation. We aimed to study the relation between prolactin levels, coagulation factors and risk of venous thrombosis (VT). We used data from a large population based case-control study into aetiology of first VT (MEGA-study). Prolactin level

  5. A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

    Science.gov (United States)

    Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

    2012-12-01

    Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII. PMID:23244324

  6. 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

  7. Crystallization and preliminary crystallographic data for a ternary complex between tissue factor, factor VIIa and a BPTI-derived inhibitor

    Science.gov (United States)

    Stura, Enrico A.; Ruf, Wolfram; Wilson, Ian A.

    1996-10-01

    The binding of tissue factor (TF) with the serine protease coagulation factor VIIa (VIIa) is the initial trigger for activation of the coagulation protease cascades. In complex with TF, VIIa has profoundly enhanced function in the limited proteolytic activation of the natural substrate factors X and IX. Here we report the screening and identification of crystallization conditions to produce diffraction quality crystals of the complex between TF · VIIa and a potent inhibitor (5L 15) derived from mutagenesis of the bovine pancreatic trypsin inhibitor (BPTI) sequence. The complex crystals were obtained from the soluble extracellular domain of tissue factor, expressed in Escherichia coli as a fusion protein, VIIa expressed in mammalian cells and recombinant 5L15. Because only 1.5 mg of complex were available for this work, a reverse screening based strategy was used in the search and optimization of the crystallization conditions. Two different crystal forms were obtained from polyethylene glycol 4000 and monomethyl polyethylene glycol 2000 with cacodylate buffer at pH 6.5 in the presence of sodium and calcium ions. The addition of magnesium and zinc have profound effects on the crystallization. Both crystal forms are trigonal with cell parameters a = b = 129.3 Å, c = 110.8 Å and a = b = 67.2 Å, c = 314.8 Å diffracting to 7 and 3.2 Å resolution, respectively, each with one molecule in the asymmetric unit. Complete data sets have been collected from each of these forms to the resolution to which the crystals diffract. A structural understanding of the interaction of VIIa with its cofactor TF to form a binary enzyme, and its inhibition by 5L15 will provide a basis for the development of antithrombotic strategies.

  8. Fresh frozen plasma in the pediatric age group and in congenital coagulation factor deficiency.

    Science.gov (United States)

    Muntean, Wolfgang

    2002-10-31

    Generally, the rules of good practice in transfusion medicine apply also to the pediatric age group. However, the frequency of specific diseases that might necessitate the administration of fresh frozen plasma (FFP) differs from that in adults. Physiologic differences to the later age exist in the neonatal period and in young infants, especially with respect to the hemostatic system, that must be recognized when considering administration of FFP. The plasma levels of many procoagulant factors and important anticoagulants are lower in neonates than in other age groups. Despite these findings, healthy neonates show no easy bruising, no increased bleeding during surgery, and excellent wound healing. The same discrepancy obtains between in vitro and clinical findings with primary hemostasis in neonates. The good primary hemostasis in neonates despite poor in vitro platelet function seems to be due mainly to a very high von Willebrand factor and the presence of more high-multimeric subunits of von Willebrand factor than later in life. We must assume that these particular plasma levels of procoagulant and anticoagulant proteins are essential for the correct function of neonatal hemostasis. Evidence that the hemostatic system of neonates works best with physiologic concentrations of procoagulants and anticoagulants can also be inferred from studies where the administration of clotting factor concentrates gave poor results.Since healthy neonates and young infants have excellent hemostasis, there is absolutely no indication to 'correct' these values to adult's norms prior to invasive procedures by administering FFP. Indications for FFP, met more frequently in the pediatric age group than later in life, are exchange transfusion and extracorporeal membrane oxygenation. Indications applying equally to adults are other extracorporeal life support systems, disseminated intravascular coagulation, hepatic coagulopathy, and 'complex unclear coagulopathies'. In congenital clotting

  9. Pharmacogenetic typing for oral anti-coagulant response among factor V Leiden mutation carriers

    Directory of Open Access Journals (Sweden)

    Risha Nahar

    2012-01-01

    Conclusions: Pre-prescription genotyping for coumarin drugs, if introduced in Indians with inherited thrombophilia (in whom oral anti-coagulant therapy may be necessary, is likely to identify 9.7% (hypersensitive subjects in whom the optimum anti-coagulation may be achieved with reduced dosages, 44.3% (normal sensitivity who may require higher dose and also 55.6% (hyper and moderate sensitivity subjects who are likely to experience bleeding episodes.

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

    Institute of Scientific and Technical Information of China (English)

    Chunde Wu; Lin Wang; Bing Hu; Jian Ye

    2013-01-01

    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.

  11. Levels of acarboxy prothrombin (PIVKA-II) and coagulation factors in warfarin-treated patients.

    Science.gov (United States)

    Umeki, S; Umeki, Y

    1990-04-01

    PIVKA-II (protein induced by vitamin K absence or antagonists-II) was determined and compared with other coagulation factors in normal subjects and patients treated with the anticoagulant warfarin. In 18 (60%) of 30 patients treated with warfarin, PIVKA-II values were 1 microgram/ml or more, although they were less than 1 microgram/ml in all 39 normal subjects (100%). In patients treated with warfarin, values of prothrombin time and partial thromboplastin time were significantly higher than those in normal subjects. However, values of hepaplastintest (normotest) and thrombotest in the patients were greatly lower than those in normal subjects. There were no significant differences between bleeding time or plasma fibrinogen values in the patients and normal subjects. The values of PIVKA-II were inversely correlated (P less than 0.01) with those of hepaplastintest and thrombotest. The measurement of PIVKA-II in the plasma should be useful in detecting vitamin K-deficient status among haemorrhagic disorders.

  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. VASCULAR ENDOTHELIAL INJURIES AND CHANGES OF BLOOD COAGULATION AND FIBRINOLYSIS INDEXES IN PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME

    Institute of Scientific and Technical Information of China (English)

    Xiao-lin He; Zhi Liu; Shu-yue Xia

    2004-01-01

    Objective To study endothelial damage by observing changes of circulating endothelial cells (CECs) in blood, coagulation and fibrinolysis index in patients with acute respiratory distress syndrome.Methods CECs were separated by isopycnic centrifugation method in 14 patients with acute lung injury (ALI), 7patients with acute respiratory distress syndrome (ARDS), 10 intensive care unit (ICU) controls, and 15 healthy controls.Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FG), fibrin degradation products (FDP), and D-dimer were examined simultaneously. Acute physiology and chronic health evaluation (APACHE) Ⅱ and lung injury score (LIS) were recorded to evaluate severity of illness and lung injury.Results (1) The number of CECs in ALI (10.4 ± 2.3 ) and ARDS groups ( 16.1 ± 2.7) was higher than that in the healthy (1.9 ± 0.5) (P < 0.01). In both ALI and ARDS, the number of CECs correlated with APACHE Ⅱ (r = 0.55, P < 0.05 and r =0.62, P < 0.05, respectively) and LIS (r = 0.60, P < 0.05 and r = 0.53, P < 0.05, respectively). CEC number was negatively correlated with PaO2 in ALI and ARDS (r=-0.49, P< 0.05 and r=-0.64, P< 0.05, respectively). (2) The level of FDP and D-dirmer were higher in ALI and ARDS patients than that in ICU and healthy control groups (P<0.05). The level of FG in ARDS group was significantly higher than in the ICU and healthy control groups (P < 0.05). But in ALI group, the level of FG was significantly higher than only healthy control group (P < 0.05).Conclusions Endothelial cell damage occurs in ARDS patients, which may play a major role in the pathophysiology of ARDS. Changes of endothelial cell activation and damage markers, such as CECs, plasma coagulation and fibrinolysis index,to some extent reflect severity of illness and lung injury in ARDS.

  14. Pathogen inactivation in fresh frozen plasma using riboflavin and ultraviolet light: Effects on plasma proteins and coagulation factor VIII

    Directory of Open Access Journals (Sweden)

    Stanojković Zoran

    2011-01-01

    Full Text Available Background/Aim. Riboflavin (vitamin B2 activated by ultraviolet (UV light, produces active oxygen which damages cell membrane and prevents replication of the carrier of diseases (viruses, bacteria, protozoa in all blood products. The aim of this study was to establish the influence of the process of photo inactivation in pathogens using riboflavin and UV rays on the concentration of coagulation factor VIII:C (FVIII:C and proteins in plasma that were treated before freezing. Methods. The examination included 20 units of plasma, separated from whole blood donated by voluntary blood donors around 6 hours from the moment of collection. The units were pooled and separated in to two groups: one consisted of 10 control units and the other of 10 experimental units. Experimental units of the plasma were treated by riboflavin (35 mL and UV rays (6.24 J/mL, 265-370 nm on Mirasol aparature (Caridian BCT Biotechnologies, USA in approximate duration of 6 minutes. Furthermore, 35 mL of saline solution was added to the control plasma. One sample for examining was taken from the control plasma (KG and two residual were taken from experimental plasma after the addition of riboflavin either before (EG1 or post illumination (EG2. Results. Comparing the mean values of FVIII:C (% we noticed statistically significantly higher level in the EG1 group than in the EG2 group (65.00 ± 4.52 vs 63.20 ± 4.73; t = 4.323, p = 0.002, while between the KG and experimental groups (EG1 and EG2 there was no statistically significant difference in the concentration of FVIII:C. There was a statistically significant decrease of albumin concentration (g/L in the EG2 group comparing to the KG (33.35 ± 0.94 vs 31.94 ± 0.84; t = 3.534, p = 0.002, but there was no mentioned difference in albumin concentration between the KG and the EG1, so as between the EG1 and the EG2. Conclusion. Plasma inactivated by riboflavin and UV rays (Mirasol PRT sistem, Caridian BCT, USA keeps all the

  15. Effects of three novel metalloproteinases from the venom of the West African saw-scaled viper, Echis ocellatus on blood coagulation and platelets.

    Science.gov (United States)

    Howes, J-M; Kamiguti, A S; Theakston, R D G; Wilkinson, M C; Laing, G D

    2005-06-20

    Two metalloproteinases, a 24-kDa P-I EoVMP1 and a 56-kDa P-III EoVMP2, have recently been isolated from the venom of the West African saw-scaled viper Echis ocellatus. We now reveal a new 65-kDa haemorrhagic group P-III metalloproteinase which we have designated EoVMP3. The aim of this study was to determine whether these three snake venom metalloproteinases (SVMPs) affect platelets and blood coagulation. EoVMP1 had no effect on the aggregation of washed human platelets, whereas EoVMP2 inhibited collagen-induced platelet aggregation. In contrast, EoVMP3 did not inhibit the aggregation of platelets by collagen but instead activated platelets in the absence of any additional co-factors. All three SVMPs were capable of activating prothrombin to varying degrees and can therefore be described as procoagulants. EoVMP1, EoVMP2 and EoVMP3 share sequence identity with other members of the reprolysin family, but differ greatly in their effects on some of the components that control haemostasis. PMID:15863354

  16. Relationship between vitamin K dependent coagulation factors and anticoagulants (protein C and protein S) in neonatal vitamin K deficiency.

    OpenAIRE

    Matsuzaka, T; Tanaka, H.; Fukuda, M; Aoki, M.; Tsuji, Y; Kondoh, H

    1993-01-01

    To determine the relationship between vitamin K dependent coagulation factors and natural anticoagulants, namely protein C and protein S, in various degrees of vitamin K deficiency, plasma values for clotting activity, protein induced by vitamin K absence (PIVKA-II), protein C antigen, gamma-carboxy protein C antigen, and protein S antigen including total and free fractions and activity of protein C were measured in 66 full term and healthy breast fed neonates who did not receive vitamin K su...

  17. Proof-of-concept Studies for siRNA-mediated Gene Silencing for Coagulation Factors in Rat and Rabbit

    OpenAIRE

    Chen, Zhu; Luo, Bin; Cai, Tian-Quan; Thankappan, Anil; Xu, Yiming; Wu, Weizhen; DiMuzio, Jillian; Lifsted, Traci; DiPietro, Marty; Disa, Jyoti; Ng, Bruce; Leander, Karen; Clark, Seth; Hoos, Lizbeth; Zhou, Yuchen

    2015-01-01

    The present study aimed at establishing feasibility of delivering short interfering RNA (siRNA) to target the coagulation cascade in rat and rabbit, two commonly used species for studying thrombosis and hemostasis. siRNAs that produced over 90% mRNA knockdown of rat plasma prekallikrein and rabbit Factor X (FX) were identified from in vitro screens. An ionizable amino lipid based lipid nanoparticle (LNP) formulation for siRNA in vivo delivery was characterized as tolerable and exerting no app...

  18. ACL-TOP700血凝仪凝血4项正常参考区间的建立%Establishment of normal reference interval for four items of blood coagulation on ACL-TOP Automatic coagulation analyzer

    Institute of Scientific and Technical Information of China (English)

    陈锐; 鲁燕飞; 周志兰; 姚振国; 陈国强

    2015-01-01

    Objective To establish normal reference interval for four items of blood coagulation on ACL‐TOP Automatic coagu‐lation analyzer .Methods The fasting anti‐coagulation blood samples were collected from 1 268 inpatients and people conducted physical examination ,all subjects without liver disease ,history of blood disease and coagulation disfunction .The prothrombin time (PT) ,activated partical prothrombin time(APTT) ,thrombin time(TT) and serum levels of fibrinogen(FIB) were determined by u‐sing ACL‐TOP automatic coagulation analyzer which was producted by America IL company .And data of determination results were used to establish the normal reference intervals of indexes in this laboratory .Results The precision and accuracy of this analy‐zer was good .There were differences of normal reference intervals between which established in this laboratory and which provided by the manufacturer .Conclusion Each laboratory should establish its own normal reference interval ,not blindly refer to reference interval provided by regents manual .%目的:建立ACL‐TOP700全自动血凝分析仪本实验室凝血4项的正常参考区间。方法筛选1268住院患者及门诊体检者,均无肝病、血液病史及出凝血功能障碍,空腹采集其静脉抗凝血。采用美国IL公司生产的ACL‐TOP700全自动血凝分析仪进行凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)测定,建立本实验室 PT、APTT、TT、FIB的正常参考区间。结果该仪器精密度、正确度均良好,各参考区间与厂家提供的参考区间有一定的差异。结论各个实验室应建立自己的参考区间,不可盲目引用厂家试剂说明书上提供的正常参考区间。

  19. Aestivation induces changes in transcription and translation of coagulation factor II and fibrinogen gamma chain in the liver of the African lungfish Protopterus annectens.

    Science.gov (United States)

    Hiong, Kum C; Tan, Xiang R; Boo, Mel V; Wong, Wai P; Chew, Shit F; Ip, Yuen K

    2015-12-01

    This study aimed to sequence and characterize two pro-coagulant genes, coagulation factor II (f2) and fibrinogen gamma chain (fgg), from the liver of the African lungfish Protopterus annectens, and to determine their hepatic mRNA expression levels during three phases of aestivation. The protein abundance of F2 and Fgg in the liver and plasma was determined by immunoblotting. The results indicated that F2 and Fgg of P. annectens were phylogenetically closer to those of amphibians than those of teleosts. Three days of aestivation resulted in an up-regulation in the hepatic fgg mRNA expression level, while 6 days of aestivation led to a significant increase (3-fold) in the protein abundance of Fgg in the plasma. Hence, there could be an increase in the blood-clotting ability in P. annectens during the induction phase of aestivation. By contrast, the blood-clotting ability in P. annectens might be reduced in response to decreased blood flow and increased possibility of thrombosis during the maintenance phase of aestivation, as 6 months of aestivation led to significant decreases in mRNA expression levels of f2 and fgg in the liver. There could also be a decrease in the export of F2 and Fgg from the liver to the plasma so as to avert thrombosis. Three to 6 days after arousal from 6 months of aestivation, the protein abundance of F2 and Fgg recovered partially in the plasma of P. annectens; a complete recovery of the transcription and translation of f2/F2 in the liver might occur only after refeeding.

  20. Combined collision-induced dissociation and photo-selected reaction monitoring mass spectrometry modes for simultaneous analysis of coagulation factors and estrogens

    Institute of Scientific and Technical Information of China (English)

    Quentin Enjalbert; Marion Girod; Jérémy Jeudy; Jordane Biarc; Romain Simon; Rodolphe Antoine; Philippe Dugourd; Jérôme Lemoine; Arnaud Salvador

    2014-01-01

    Oral estrogens are directly associated with changes in plasma levels of coagulation proteins. Thus, the detection of any variation in protein concentrations due to estrogen contraceptives, by a simultaneous analysis of both coagulation proteins and estrogens, would be a very informative tool. In the present study, the merit of photo-selected reaction monitoring (SRM), a new analytical tool, was evaluated towards estrogens detection in plasma. Then, SRM and photo-SRM detection modes were combined for the simultaneous analysis of estrogen molecules together with heparin co-factor and factor XIIa, two proteins involved in the coagulation cascade. This study shows that photo-SRM could open new multiplexed analytical routes.

  1. Effects on fibrinogen, fibrin, and blood coagulation of proteolytic extracts from fruits of Pseudananas macrodontes, Bromelia balansae, and B. hieronymi (Bromeliaceae) in comparison with bromelain.

    Science.gov (United States)

    Errasti, María E; Prospitti, Anabela; Viana, Carolina A; Gonzalez, Mariana M; Ramos, Márcio V; Rotelli, Alejandra E; Caffini, Néstor O

    2016-06-01

    Extracts rich in cysteine proteases obtained from fruits of Pseudananas macrodontes (Pm), Bromelia balansae (Bb), and B. hieronymi (Bh) have previously shown an anti-inflammatory effect on animal models. Given the close relationship between hemostasis and inflammation, it is attractive to investigate therapeutic agents capable of modulating both systems. The aim of this work was to study the effect of Pm, Bb, and Bh on fibrin(ogen) and blood coagulation compared with stem bromelain (Bro). Action on fibrinogen was electrophoretically and spectrophotometrically evaluated, fibrinolytic activity was measured both electrophoretically and by the fibrin plate assay, and the effect on blood coagulation was studied by conventional coagulation tests (PT and APPT). All extracts showed the same proteolytic preference for fibrinogen subunits, that is Aα > Bβ, whereas γ was partially hydrolyzed by 100-fold concentration increase. Unlike Bro, cysteine proteases of Pm, Bb, and Bh increased absorbance at 540 nm of fibrinogen solution, suggesting thrombin-like activity, which was time-dependent and reached maximum values at lower concentration. All extracts showed the same proteolytic preference for fibrin subunits; however Pm, Bb, and Bh showed lower fibrinolytic activity than Bro at the assayed concentrations. Although Bb acted only as anticoagulant, Pm, Bh, and unexpectedly Bro showed dual action on blood coagulation: at low concentration showed procoagulant effect and at high concentration anticoagulant effect. Results reveal new plant species as potential sources of pharmacological agents for the treatment of a wide range of hemostatic disorders as well as to wound healing. PMID:26886361

  2. Enhancement of fibrinogen-triggered pro-coagulant activation of monocytes in vitro by matrix metalloproteinase-9

    Directory of Open Access Journals (Sweden)

    Feistritzer Clemens

    2010-01-01

    Full Text Available Abstract Background Interaction of fibrinogen with specific leukocyte integrins of monocytes may link coagulation and inflammation, however, the precise mechanism of fibrinogen leading to the pro-inflammatory and pro-coagulatory response on monocytes is yet unknown. Results Fibrinogen and its digestion fragment D induced pro-coagulant activation of monocytes as assessed in a cellular coagulation assay by reductions in clotting times. Pro-coagulant activation was reversed by blocking antibodies against Mac-1 or LFA-1. Pre-exposure of monocytes to the p38 MAPK inhibitor SB 202190 and the MEK1.2 inhibitor U0126 led to significant increasees in coagulation times whereas blocking JNKII with its inhibitor had no such effect. Blocking NFκB with MG-132 also inhibited pro-coagulant activation of monocytes by fibrinogen. A selective inhibitor of matrix metalloproteinase-9 increased times to clot formation whereas other matrix metalloproteinase inhibitors did not significantly interfere with fibrinogen-augmented clot formation in this assay. Treatment of monocytes with fibrinogen increased concentrations of matrix metalloproteinase-9 immunoreactivity in their supernatants. Conclusions Fibrinogen induces monocyte pro-coagulant activation in an integrin-, nuclear factor κB-, p38 MAPK-, and MEK1.2-dependent manner. Activation of monocytes by fibrinogen increases metalloproteinase-9 secretion, metalloproteinase-9 itself enhances monocyte coagulation by an autocrine mechanism. Results provide further evidence that mediators of hemostasis have a profound impact on cells of the immune system and are closely related to inflammatory pathways.

  3. In silico designing of hyper-glycosylated analogs for the human coagulation factor IX.

    Science.gov (United States)

    Ghasemi, Fahimeh; Zomorodipour, Alireza; Karkhane, Ali Asghar; Khorramizadeh, M Reza

    2016-07-01

    N-glycosylation is a process during which a glycan moiety attaches to the asparagine residue in the N-glycosylation consensus sequence (Asn-Xxx-Ser/Thr), where Xxx can be any amino acid except proline. Introduction of a new N-glycosylation site into a protein backbone leads to its hyper-glycosylation, and may improve the protein properties such as solubility, folding, stability, and secretion. Glyco-engineering is an approach to facilitate the hyper-glycosylation of recombinant proteins by application of the site-directed mutagenesis methods. In this regard, selection of a suitable location on the surface of a protein for introduction of a new N-glycosylation site is a main concern. In this work, a computational approach was conducted to select suitable location(s) for introducing new N-glycosylation sites into the human coagulation factor IX (hFIX). With this aim, the first 45 residues of mature hFIX were explored to find out suitable positions for introducing either Asn or Ser/Thr residues, to create new N-glycosylation site(s). Our exploration lead to detection of five potential positions, for hyper-glycosylation. For each suggested position, an analog was defined and subjected for N-glycosylation efficiency prediction. After generation of three-dimensional structures, by homology-based modeling, the five designed analogs were examined by molecular dynamic (MD) simulations, to predict their stability levels and probable structural distortions caused by amino acid substitutions, relative to the native counterpart. Three out of five suggested analogs, namely; E15T, K22N, and R37N, reached equilibration state with relatively constant Root Mean Square Deviation values. Additional analysis on the data obtained during MD simulations, lead us to conclude that, R37N is the only qualified analog with the most similar structure and dynamic behavior to that of the native counterpart, to be considered for further experimental investigations. PMID:27356208

  4. Major Risk Factors for Heart Disease: High Blood Cholesterol

    Science.gov (United States)

    ... Major Risk Factors for Heart Disease High Blood Cholesterol High blood cholesterol is another major risk factor for heart disease ... can do something about. The higher your blood cholesterol level, the greater your risk for developing heart ...

  5. Proof-of-concept Studies for siRNA-mediated Gene Silencing for Coagulation Factors in Rat and Rabbit

    Science.gov (United States)

    Chen, Zhu; Luo, Bin; Cai, Tian-Quan; Thankappan, Anil; Xu, Yiming; Wu, Weizhen; DiMuzio, Jillian; Lifsted, Traci; DiPietro, Marty; Disa, Jyoti; Ng, Bruce; Leander, Karen; Clark, Seth; Hoos, Lizbeth; Zhou, Yuchen; Jochnowitz, Nina; Jachec, Christine; Szczerba, Peter; Gindy, Marian E.; Strapps, Walter; Sepp-Lorenzino, Laura; Seiffert, Dietmar A.; Lubbers, Laura; Tadin-Strapps, Marija

    2015-01-01

    The present study aimed at establishing feasibility of delivering short interfering RNA (siRNA) to target the coagulation cascade in rat and rabbit, two commonly used species for studying thrombosis and hemostasis. siRNAs that produced over 90% mRNA knockdown of rat plasma prekallikrein and rabbit Factor X (FX) were identified from in vitro screens. An ionizable amino lipid based lipid nanoparticle (LNP) formulation for siRNA in vivo delivery was characterized as tolerable and exerting no appreciable effect on coagulability at day 7 postdosing in both species. Both prekallikrein siRNA-LNP and FX siRNA-LNP resulted in dose-dependent and selective knockdown of target gene mRNA in the liver with maximum reduction of over 90% on day 7 following a single dose of siRNA-LNP. Knockdown of plasma prekallikrein was associated with modest clot weight reduction in the rat arteriovenous shunt thrombosis model and no increase in the cuticle bleeding time. Knockdown of FX in the rabbit was accompanied with prolongation in ex vivo clotting times. Results fit the expectations with both targets and demonstrate for the first time, the feasibility of targeting coagulation factors in rat, and, more broadly, targeting a gene of interest in rabbit, via systemic delivery of ionizable LNP formulated siRNA. PMID:25625614

  6. Monocyte tissue factor-dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin.

    Science.gov (United States)

    Owens, A Phillip; Passam, Freda H; Antoniak, Silvio; Marshall, Stephanie M; McDaniel, Allison L; Rudel, Lawrence; Williams, Julie C; Hubbard, Brian K; Dutton, Julie-Ann; Wang, Jianguo; Tobias, Peter S; Curtiss, Linda K; Daugherty, Alan; Kirchhofer, Daniel; Luyendyk, James P; Moriarty, Patrick M; Nagarajan, Shanmugam; Furie, Barbara C; Furie, Bruce; Johns, Douglas G; Temel, Ryan E; Mackman, Nigel

    2012-02-01

    Hypercholesterolemia is a major risk factor for atherosclerosis. It also is associated with platelet hyperactivity, which increases morbidity and mortality from cardiovascular disease. However, the mechanisms by which hypercholesterolemia produces a procoagulant state remain undefined. Atherosclerosis is associated with accumulation of oxidized lipoproteins within atherosclerotic lesions. Small quantities of oxidized lipoproteins are also present in the circulation of patients with coronary artery disease. We therefore hypothesized that hypercholesterolemia leads to elevated levels of oxidized LDL (oxLDL) in plasma and that this induces expression of the procoagulant protein tissue factor (TF) in monocytes. In support of this hypothesis, we report here that oxLDL induced TF expression in human monocytic cells and monocytes. In addition, patients with familial hypercholesterolemia had elevated levels of plasma microparticle (MP) TF activity. Furthermore, a high-fat diet induced a time-dependent increase in plasma MP TF activity and activation of coagulation in both LDL receptor-deficient mice and African green monkeys. Genetic deficiency of TF in bone marrow cells reduced coagulation in hypercholesterolemic mice, consistent with a major role for monocyte-derived TF in the activation of coagulation. Similarly, a deficiency of either TLR4 or TLR6 reduced levels of MP TF activity. Simvastatin treatment of hypercholesterolemic mice and monkeys reduced oxLDL, monocyte TF expression, MP TF activity, activation of coagulation, and inflammation, without affecting total cholesterol levels. Our results suggest that the prothrombotic state associated with hypercholesterolemia is caused by oxLDL-mediated induction of TF expression in monocytes via engagement of a TLR4/TLR6 complex. PMID:22214850

  7. Role of heparin and non heparin binding serpins in coagulation and angiogenesis: A complex interplay.

    Science.gov (United States)

    Bhakuni, Teena; Ali, Mohammad Farhan; Ahmad, Irshad; Bano, Shadabi; Ansari, Shoyab; Jairajpuri, Mohamad Aman

    2016-08-15

    Pro-coagulant, anti-coagulant and fibrinolytic pathways are responsible for maintaining hemostatic balance under physiological conditions. Any deviation from these pathways would result in hypercoagulability leading to life threatening diseases like myocardial infarction, stroke, portal vein thrombosis, deep vein thrombosis (DVT) and pulmonary embolism (PE). Angiogenesis is the process of sprouting of new blood vessels from pre-existing ones and plays a critical role in vascular repair, diabetic retinopathy, chronic inflammation and cancer progression. Serpins; a superfamily of protease inhibitors, play a key role in regulating both angiogenesis and coagulation. They are characterized by the presence of highly conserved secondary structure comprising of 3 β-sheets and 7-9 α-helices. Inhibitory role of serpins is modulated by binding to cofactors, specially heparin and heparan sulfate proteoglycans (HSPGs) present on cell surfaces and extracellular matrix. Heparin and HSPGs are the mainstay of anti-coagulant therapy and also have therapeutic potential as anti-angiogenic inhibitors. Many of the heparin binding serpins that regulate coagulation cascade are also potent inhibitors of angiogenesis. Understanding the molecular mechanism of the switch between their specific anti-coagulant and anti-angiogenic role during inflammation, stress and regular hemostasis is important. In this review, we have tried to integrate the role of different serpins, their interaction with cofactors and their interplay in regulating coagulation and angiogenesis.

  8. Role of heparin and non heparin binding serpins in coagulation and angiogenesis: A complex interplay.

    Science.gov (United States)

    Bhakuni, Teena; Ali, Mohammad Farhan; Ahmad, Irshad; Bano, Shadabi; Ansari, Shoyab; Jairajpuri, Mohamad Aman

    2016-08-15

    Pro-coagulant, anti-coagulant and fibrinolytic pathways are responsible for maintaining hemostatic balance under physiological conditions. Any deviation from these pathways would result in hypercoagulability leading to life threatening diseases like myocardial infarction, stroke, portal vein thrombosis, deep vein thrombosis (DVT) and pulmonary embolism (PE). Angiogenesis is the process of sprouting of new blood vessels from pre-existing ones and plays a critical role in vascular repair, diabetic retinopathy, chronic inflammation and cancer progression. Serpins; a superfamily of protease inhibitors, play a key role in regulating both angiogenesis and coagulation. They are characterized by the presence of highly conserved secondary structure comprising of 3 β-sheets and 7-9 α-helices. Inhibitory role of serpins is modulated by binding to cofactors, specially heparin and heparan sulfate proteoglycans (HSPGs) present on cell surfaces and extracellular matrix. Heparin and HSPGs are the mainstay of anti-coagulant therapy and also have therapeutic potential as anti-angiogenic inhibitors. Many of the heparin binding serpins that regulate coagulation cascade are also potent inhibitors of angiogenesis. Understanding the molecular mechanism of the switch between their specific anti-coagulant and anti-angiogenic role during inflammation, stress and regular hemostasis is important. In this review, we have tried to integrate the role of different serpins, their interaction with cofactors and their interplay in regulating coagulation and angiogenesis. PMID:27372899

  9. Analysis of the factor Ⅻ gene mutation in a Chinese pedigree with congenital blood coagulation factor Ⅻ deficiency%一个遗传性凝血因子Ⅻ缺陷症家系凝血因子Ⅻ基因分析

    Institute of Scientific and Technical Information of China (English)

    谢海啸; 王明山; 谢耀盛; 周武; 杨丽红; 金艳慧; 潘荣杰

    2010-01-01

    Objective To analyze FⅫ gene mutation and investigate the molecular mechanism of FⅫ in a Chinese pedigree with congenital FⅫ deficiency.Methods The plasma aPTT,FⅫ activity and FⅫ antigen were detected.The exons 1-14,boundary intmns including the splice junctions of FⅫ gene of the FⅫ deficiency Pedigree members were amplified by PCR The PCR products were purified and sequenced directly.The sequencing was perform with reverse primer if the gene mutations were found.One hundred healthy persons were used as normal controls.Results The proband and the younger brother manifested prolonged aPTT(79.1 s/35 s,84.6 s/35 s respectively).The aPTT result of the older son was 42.1 s/35 s.slightly higher than the normal level.The levels of other members were in normal range.The FⅫ activities of the proband and the younger brother were as low as 2% and 3% respectively,and the levels of FⅫantigen were <1%.The FⅫ activities of his older brother.the older and the younger son were 39%.29%,34% respectively.And the levels of FⅫ antigen were 32%,30%,37% respectively.In the promoter regions of FⅫ gene,the genotype of the proband and the younger brother was 46T/T.And in exon5 for the proband and the younger brother,there was mutations of 5741deleteC and 5742deleteA,resulting in Ser400Pro.And in exon10,there was an insertion mutation 7142insertC,resulting in one missense mutation Lys346Gln(K346Q).In the other members of the family,the older brother and the two sons harbored 46T/T and 7142insertC.And the little granddaughter had 46T/T and the geuotype of the niece and the two older granddaughters was 46C/T.Conclusions In the congenital factor Ⅻ deficiency pedigree,there was a common 46C→T polymorphism in promoter region of FⅫ gene.There was 5741deleteC and 5742deleteA in exon 5 and 7142insertC in exon 10.The mutations of 5741deleteC,5742deleteA and 7142insertC were attributed to decrease in the levels of Factor Ⅻ.%目的 对一个遗

  10. A selective, slow binding inhibitor of factor VIIa binds to a nonstandard active site conformation and attenuates thrombus formation in vivo.

    Science.gov (United States)

    Olivero, Alan G; Eigenbrot, Charles; Goldsmith, Richard; Robarge, Kirk; Artis, Dean R; Flygare, John; Rawson, Thomas; Sutherlin, Daniel P; Kadkhodayan, Saloumeh; Beresini, Maureen; Elliott, Linda O; DeGuzman, Geralyn G; Banner, David W; Ultsch, Mark; Marzec, Ulla; Hanson, Stephen R; Refino, Canio; Bunting, Stuart; Kirchhofer, Daniel

    2005-03-11

    The serine protease factor VIIa (FVIIa) in complex with its cellular cofactor tissue factor (TF) initiates the blood coagulation reactions. TF.FVIIa is also implicated in thrombosis-related disorders and constitutes an appealing therapeutic target for treatment of cardiovascular diseases. To this end, we generated the FVIIa active site inhibitor G17905, which displayed great potency toward TF.FVIIa (Ki = 0.35 +/- 0.11 nM). G17905 did not appreciably inhibit 12 of the 14 examined trypsin-like serine proteases, consistent with its TF.FVIIa-specific activity in clotting assays. The crystal structure of the FVIIa.G17905 complex provides insight into the molecular basis of the high selectivity. It shows that, compared with other serine proteases, FVIIa is uniquely equipped to accommodate conformational disturbances in the Gln217-Gly219 region caused by the ortho-hydroxy group of the inhibitor's aminobenzamidine moiety located in the S1 recognition pocket. Moreover, the structure revealed a novel, nonstandard conformation of FVIIa active site in the region of the oxyanion hole, a "flipped" Lys192-Gly193 peptide bond. Macromolecular substrate activation assays demonstrated that G17905 is a noncompetitive, slow-binding inhibitor. Nevertheless, G17905 effectively inhibited thrombus formation in a baboon arterio-venous shunt model, reducing platelet and fibrin deposition by approximately 70% at 0.4 mg/kg + 0.1 mg/kg/min infusion. Therefore, the in vitro potency of G17905, characterized by slow binding kinetics, correlated with efficacious antithrombotic activity in vivo. PMID:15632123

  11. 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

  12. The Association of Coagulation Factor V (Leiden) and Factor II (Prothrombin) Mutations With Stroke

    Science.gov (United States)

    Pirhoushiaran, Maryam; Ghasemi, Mohammad Reza; Hami, Javad; Zargari, Peyman; Sasan Nezhad, Payam; Azarpazhooh, Mahmood Reza; Sadr Nabavi, Ariane

    2014-01-01

    Background: Epidemiological studies indicate that over the past forty years, the stroke incidence rates has increased. Factors V and II mutations are established genetic-variant risk factors for venous thrombosis; however, their contribution to stroke is a controversial issue. Objectives: This study aimed to investigate the potential association of FV and FII mutations with stroke in an Iranian population. Patients and Methods: The study population consisted of 153 patients of different stroke subtypes (except cryptogenic strokes), admitted to Ghaem Hospital, Mashhad, Iran. The control group included 153 age- and sex-matched subjects without a history of cerebrovascular or neurologic diseases. Mutations of FV and FII were determined by using a TaqMan SNP Genotyping technique. The chi-square and Exact Fisher tests were used to analyze the baseline characteristics. Results were as follows: The calculated P-value for sex and diabetes mellitus were 0.907 and 1.000, respectively. The case and control groups were also matched in low density lipoprotein (P = 0.816), high density lipoprotein (P = 0.323), triglyceride (P = 0.846), and total cholesterol (P = 0.079). Results: Analysis of the FV showed that none of the study subjects were AA homozygous for this mutation and only 6 heterozygous subjects were detected in the case and control groups. Regarding FII variants, none of the study subjects were AG heterozygous and only 1 AA homozygous was detected in the control group. Conclusions: The prevalence of both FV and FII variants are population based. Iran is an ethnically diverse country. Therefore, for a comprehensive analysis of a potential association of FV and/or FII mutations with stroke among Iranian population, epidemiological studies could be conducted among different ethnic groups. PMID:25763204

  13. Research of Polyphosphate and Coagulation%多聚磷酸盐与凝血的研究现状

    Institute of Scientific and Technical Information of China (English)

    丁文博; 孟焕(综述); 果怡博; 寇俊杰(审校)

    2016-01-01

    无机多聚磷酸盐在体内分布广泛,是一个强力的天然病理生理性内源性凝血促进剂,其能够加速凝血因子Ⅴ的活化,并完全废除组织因子通道抑制剂的抗凝作用,同时增强纤维蛋白的结构稳定性,反向激活凝血因子Ⅺ。多聚磷酸盐可以作为强效的止血剂,同时其拮抗剂也可以作为新型的抗凝剂,但是多聚磷酸盐详细的调节机制仍有待研究。%Inorganic polyphosphate is widespread in body,and it is a natural pathophysiologic intrinsic accelerant of blood coagulation,which can accelerate coagulation factor Ⅴactivation,and completely abrogate the anticoagulant function of tissue factor pathway inhibitor,enhancinh fibrin structural stability and activa-ting coagulation factorⅪ backwards.Polyphosphate can be used as a hemostatic agent,and its antagonist can be used as a new anticoagulants, though the detailed mechanisms of polyphosphate with blood clotting reactions still need tfurther study.

  14. Antithrombin inhibits bronchoalveolar activation of coagulation and limits lung injury during Streptococcus pneumoniae pneumonia in rats

    NARCIS (Netherlands)

    Choi, Goda; Hofstra, Jorrit-Jan H; Roelofs, Joris J T H; Rijneveld, Anita W; Bresser, Paul; van der Zee, Jaring S; Florquin, Sandrine; van der Poll, Tom; Levi, Marcel; Schultz, Marcus J

    2008-01-01

    OBJECTIVE: Alveolar fibrin deposition is a hallmark of pneumonia. It has been proposed that natural inhibitors of coagulation, including activated protein C, antithrombin, and tissue factor pathway inhibitor, exert lung-protective effects via anticoagulant and possibly anti-inflammatory pathways. We

  15. Dynamics of change of lipid and monoamine metabolisms and the blood coagulation system during experimental atherosclerosis caused by restriction of movement

    Science.gov (United States)

    Gvishiani, G. S.; Kobakhidze, N. G.

    1980-01-01

    Shifts in lipid, catecholamine, and blood coagulation systems following various periods (1, 2, 3, and 4 months) of experimentally induced atherosclerosis were studied. The same indices were studied in the tissues of the myocardium, liver, and brain stem-reticular formation after decapitation of the animals at the end of the experiment. Periodic motion restriction caused an increase in blood beta-lipoproteins in the rabbits at the beginning of the experiment. An increase in general cholesterol content and a decrease in the lecithincholesterol index were established at the end of the experiment. Myocardial beta-lipoprotein and brain stem reticular formation general cholesterol contents were elevated; catecholamine content was increased at the end of the experiment. In the initial months, free adrenaline basically increased, while in later months blood adrenaline decreased and blood noradrenaline increased.

  16. Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? A prospective observational study

    DEFF Research Database (Denmark)

    Johansson, Per Ingemar; Sorensen, Anne Marie; Perner, Anders;

    2011-01-01

    ABSTRACT: INTRODUCTION: It is debated whether the early trauma induced coagulopathy (TIC) in severely injured patients reflects disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype, acute coagulopathy of trauma shock (ACoTS) or yet other entities. This study investigated......-complexed DNA fragments, Annexin V, thrombomodulin, syndecan-1), coagulation activation/inhibition (prothrombinfragment 1+2, thrombin/antithrombin-complexes, antithrombin, protein C, activated protein C, endothelial protein C receptor, protein S, tissue factor pathway inhibitor, vWF), factor consumption...

  17. Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? A prospective observational study

    DEFF Research Database (Denmark)

    Johansson, Per Ingemar; Sorensen, Anne Marie; Perner, Anders;

    2011-01-01

    -complexed DNA fragments, Annexin V, thrombomodulin, syndecan-1), coagulation activation/inhibition (prothrombinfragment 1+2, thrombin/antithrombin-complexes, antithrombin, protein C, activated protein C, endothelial protein C receptor, protein S, tissue factor pathway inhibitor, vWF), factor consumption......ABSTRACT: INTRODUCTION: It is debated whether the early trauma induced coagulopathy (TIC) in severely injured patients reflects disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype, acute coagulopathy of trauma shock (ACoTS) or yet other entities. This study investigated...

  18. Etiopathogenesis of Sheehan’s Syndrome: Roles of Coagulation Factors and TNF-Alpha

    Directory of Open Access Journals (Sweden)

    Halit Diri

    2014-01-01

    Full Text Available Sheehan’s Syndrome (SS is defined as pituitary hormone deficiency due to ischemic infarction of the pituitary gland as a result of massive postpartum uterine hemorrhage. Herein, we aimed to investigate the roles of Factor II (G20210A, Factor V (G1691A, MTHFR (C677T and A1298C, PAI-1 4G/5G, and TNF-α (-308  G>A gene polymorphisms in the etiopathogenesis of SS. Venous blood samples were obtained from 53 cases with SS and 43 healthy women. Standard methods were used to extract the genomic DNAs. Factor II (G20210A, Factor V (G1691A, and MTHFR (C677T and A1298C polymorphisms were identified by real-time PCR. PAI-1 4G/5G and TNF-α (-308  G>A gene polymorphisms were detected with polymerase chain reaction (PCR and restriction fragment length polymorphism (RFLP methods. According to statistical analysis, none of the polymorphisms were found to be significantly higher in the SS group compared to the control group. Hence, we suggest that genetic factors other than Factor II, Factor V, MTHFR, PAI-1, and TNF-α gene polymorphisms should be researched in the etiopathogenesis of SS.

  19. 临产孕妇凝血功能检测的临床意义%Clinical significance of detecting the function of blood coagulation for parturient women

    Institute of Scientific and Technical Information of China (English)

    王莉; 李耀军

    2011-01-01

    To study the function of coagulation, anti coagulation and fibrinolysis in later pregnant women, and to study the clinical value of prothrombin time (PT), activated partial thrombopastin time ( APTT), thrombin time (TT), fibrinogen (Fib) in later pregnant women. Methods The difference of function of blood coagulation between 320 parturient women and 130 healthy women without pregnant were analyzed. Results The results of PT,APTT and TT in the later pregnant women were low er than those in healthy controls(P<0.05). The concentration of Fib in later pregnant women were significantly higher than that in healthy controls(P<0.05). Conclusion In the process of parturition,it is important to detect the function of blood coagulation for parturient woman,especially when parturient woman shows abnormal bleeding.%目的 了解孕妇分娩前的凝血功能,探讨临产孕妇检测凝血酶原时间(PT)、活化部分凝血酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(Fib)的临床意义.方法 对320例临产孕妇和130例健康非孕妇女的凝血四项指标检测结果进行比较分析.结果 临产孕妇与健康非孕妇女比较,PT、APTT、TT显著降低,Fib明显升高,差异均有统计学意义(P<0.05).结论 在产前及分娩过程中及时监测各项凝血指标对预测、预防和治疗产妇异常出血有重要意义.

  20. The Role of Putative Phosphatidylserine-Interactive Residues of Tissue Factor on Its Coagulant Activity at the Cell Surface.

    Directory of Open Access Journals (Sweden)

    Shabbir A Ansari

    Full Text Available Exposure of phosphatidylserine (PS on the outer leaflet of the cell membrane is thought to play a critical role in tissue factor (TF decryption. Recent molecular dynamics simulation studies suggested that the TF ectodomain may directly interact with PS. To investigate the potential role of TF direct interaction with the cell surface phospholipids on basal TF activity and the enhanced TF activity following the decryption, one or all of the putative PS-interactive residues in the TF ectodomain were mutated and tested for their coagulant activity in cell systems. Out of the 9 selected TF mutants, five of them -TFS160A, TFS161A, TFS162A, TFK165A, and TFD180A- exhibited a similar TF coagulant activity to that of the wild-type TF. The specific activity of three mutants, TFK159A, TFS163A, and TFK166A, was reduced substantially. Mutation of the glycine residue at the position 164 markedly abrogated the TF coagulant activity, resulting in ~90% inhibition. Mutation of all nine lipid binding residues together did not further decrease the activity of TF compared to TFG164A. A similar fold increase in TF activity was observed in wild-type TF and all TF mutants following the treatment of THP-1 cells with either calcium ionomycin or HgCl2, two agents that are commonly used to decrypt TF. Overall, our data show that a few select TF residues that are implicated in interacting with PS contribute to the TF coagulant activity at the cell surface. However, our data also indicate that TF regions outside of the putative lipid binding region may also contribute to PS-dependent decryption of TF.

  1. The Role of Putative Phosphatidylserine-Interactive Residues of Tissue Factor on Its Coagulant Activity at the Cell Surface.

    Science.gov (United States)

    Ansari, Shabbir A; Pendurthi, Usha R; Sen, Prosenjit; Rao, L Vijaya Mohan

    2016-01-01

    Exposure of phosphatidylserine (PS) on the outer leaflet of the cell membrane is thought to play a critical role in tissue factor (TF) decryption. Recent molecular dynamics simulation studies suggested that the TF ectodomain may directly interact with PS. To investigate the potential role of TF direct interaction with the cell surface phospholipids on basal TF activity and the enhanced TF activity following the decryption, one or all of the putative PS-interactive residues in the TF ectodomain were mutated and tested for their coagulant activity in cell systems. Out of the 9 selected TF mutants, five of them -TFS160A, TFS161A, TFS162A, TFK165A, and TFD180A- exhibited a similar TF coagulant activity to that of the wild-type TF. The specific activity of three mutants, TFK159A, TFS163A, and TFK166A, was reduced substantially. Mutation of the glycine residue at the position 164 markedly abrogated the TF coagulant activity, resulting in ~90% inhibition. Mutation of all nine lipid binding residues together did not further decrease the activity of TF compared to TFG164A. A similar fold increase in TF activity was observed in wild-type TF and all TF mutants following the treatment of THP-1 cells with either calcium ionomycin or HgCl2, two agents that are commonly used to decrypt TF. Overall, our data show that a few select TF residues that are implicated in interacting with PS contribute to the TF coagulant activity at the cell surface. However, our data also indicate that TF regions outside of the putative lipid binding region may also contribute to PS-dependent decryption of TF. PMID:27348126

  2. 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

    International Nuclear Information System (INIS)

    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

  3. 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.

  4. Tissue factor pathway inhibitor levels in patients with homocystinuria.

    Science.gov (United States)

    Cella, G; Burlina, A; Sbarai, A; Motta, G; Girolami, A; Berrettini, M; Strauss, W

    2000-06-01

    Thrombotic events are a well-recognized complication of homocystinuria. However, the mechanisms involved in the atherogenic and thrombotic effects of homocyst(e)ine remain incompletely understood. The objective of this study was to determine the role of endothelial cell activation/damage as indicated by levels of thrombomodulin, tissue factor and tissue factor pathway inhibitor, and factor VII activity in patients with homocystinuria. Six patients with homocystinuria, nonresponsive to pyridoxine, treated only with trimethylglycine (betaine) were injected with a bolus of 20 IU/kg body weight of unfractionated commercial heparin to induce the release of tissue factor pathway inhibitor from the vascular endothelium. Tissue factor, thrombomodulin, and factor VII activity were measured by enzyme-linked immunosorbent assay and clotting assay before heparin administration. Tissue factor pathway inhibitor antigen and activity were measured before and 5 minutes after the bolus of heparin. Levels of homocyst(e)ine were elevated (patients: 144.2+/-19.2 micromol/L; controls: 10.2+/-0.9 micromol/L); however, levels of thrombomodulin, tissue factor, and tissue factor pathway inhibitor antigen were not statistically different from the control group. In contrast, tissue factor pathway inhibitor activity showed a significantly increased level (patients: 2.09+/-0.34 U/L; controls: 1.14+/-0.20 U/L; p<0.05) that was correlated with homocyst(e)ine. Factor VII activity was significantly decreased (patients: 64.7+/-5.1%; controls: 91.4+/-4.7%; p<0.05) and inversely correlated with homocyst(e)ine. After heparin the patients released higher amounts of tissue factor pathway inhibitor antigen and activity compared with the control group; however, the difference was not statistically significant. Although not treated with antithrombotic drugs, none of the patients had any thromboembolic complications after starting betaine. In addition to betaine treatment, the enhanced factor pathway

  5. Hysteresis-like binding of coagulation factors X/Xa to procoagulant activated platelets and phospholipids results from multistep association and membrane-dependent multimerization.

    Science.gov (United States)

    Podoplelova, Nadezhda A; Sveshnikova, Anastasia N; Kurasawa, James H; Sarafanov, Andrey G; Chambost, Herve; Vasil'ev, Sergey A; Demina, Irina A; Ataullakhanov, Fazly I; Alessi, Marie-Christine; Panteleev, Mikhail A

    2016-06-01

    Binding of coagulation factors X (fX) and Xa (fXa) to activated platelets is required for the formation of membrane-dependent enzymatic complexes of intrinsic tenase and prothrombinase. We carried out an in-depth characterization of fX/fXa binding to phospholipids and gel-filtered, thrombin-activated platelets. Flow cytometry, surface plasmon resonance, and computational modeling were used to investigate interactions of fX/fXa with the membranes. Confocal microscopy was employed to study fXa binding to platelet thrombi formed in flowing whole blood under arterial conditions. Binding of fX/fXa to either vesicles or procoagulant platelets did not follow a traditional one-step reversible binding model. Their dissociation was a two-step process resulting in a plateau that was up to 10-fold greater than the saturation value observed in the association experiments. Computational modeling and experimental evidence suggested that this was caused by a combination of two-step association (mainly for fX) and multimerization on the membrane (mainly for fXa). Importantly, fX formed multimers with fXa, thereby improving its retention. The same binding/dissociation hysteresis was observed for annexin V known to form trimers on the membranes. Experiments with platelets from gray syndrome patients showed that alpha-granular factor Va provided an additional high-affinity binding site for fXa that did not affect the hysteresis. Confocal microscopy observation of fXa binding to platelet thrombi in a flow chamber and its wash-out confirmed that this phenomenon persisted under physiologically relevant conditions. This suggests its possible role of "locking" coagulation factors on the membrane and preventing their inhibition in plasma and removal from thrombi by flow.

  6. The Diagnosis and Man Disseminated Intravascular Coagulation

    Institute of Scientific and Technical Information of China (English)

    Flelcher B.; Taylor.Jr

    2003-01-01

    @@ This review describes disseminated intravascular coagulation(DIC) as a syndrome in which hemostatic factors are activated and products are generated. This syndrome ranges in severity from an obvious decompensated coagulopathy (overt-DIC) to the subclinical compensated activation of hemostatic factors(non-overt DIC). Ths first part of this review emphasizes two points: First, activation of the hemostatic system is controlled by a vast network of capillaries and venules through anticoagulant and antiinflammatory regulatory factors that operate from the endothelium( e. G. , protein C and thrombomodulin, tissue factor pathway inhibitor).

  7. 直接Xa因子抑制剂贝曲沙班%Direct factor Xa inhibitor betrixaban

    Institute of Scientific and Technical Information of China (English)

    王兵; 刘颖; 刘登科; 王平保

    2015-01-01

    心脑血管疾病已成为全球致病和致死率最高的疾病之一,血栓形成是心脑血管疾病的主要诱因。传统的抗凝药物以肝素和华法林为主,但存在出血、血小板减少的明显不良反应。Xa 因子处于内源性凝血和外源性凝血通路的中心位置,并且每分子的Xa因子可活化产生约1000分子的凝血酶,Xa因子抑制剂的出现为抗凝药物的发展提供了新的方向。贝曲沙班是一种口服的直接Xa因子抑制剂,也是目前唯一经肾脏排泄最少的药物,在一系列研究中显示出良好的治疗前景。主要从贝曲沙班的药物概况、相关背景、合成路线、作用机制、临床研究等方面进行介绍。%Cardiovascular and cerebrovascular diseases have become one of the leading causes of morbidity and mortality in the world. Thrombosis is a major cause. Conventional antithrombotic therapy comprises heparin, warfarin, and so on. All these agents have a potential bleeding risk and a significant adverse reaction of thrombocytopenia. Factor Xa, presented at the juncture of the intrinsic and the extrinsic pathways, plays a pivotal role in the blood coagulation cascade, and per molecule produces thrombin approximately 1000 molecules. Factor Xa inhibitors provide a new direction for the development of anticoagnlant drugs. Betrixaban is an oral direct factor Xa inhibitor, and has the lowest renal excretion. In a series of researches, betrixaban shows a good prospect. The drug situation, background, route of synthesis, pharmacological action and clinical trials researches of betrixaban are reviewed in this paper.

  8. [Comparative blood coagulation studies in PGF2a- and 15-methyl-PGF2a-induced therapeutic abortion].

    Science.gov (United States)

    During, R; Junge, W D; Klausch, B

    1980-01-01

    In 15 pregnant women of the first trimenon of gravidity an interruption was performed by means of extra-amnial application of PGF2a and in 10 pregnant women by means of i. m. application of 15-methyl-PGF2a. Bleeding time, recalcification time, number of thrombocytes, heat fibrin, and thrombocyte adhesiveness were determined before, during and after treatment. Statistically significant changes could be observed during bleeding time, heat fibrin, and thrombocyte number. The investigations of coagulation, however, did not reveal any considerable impairment of the coagulation system, thus confirming the positive evaluation of prostaglandines used for therapeutic induction of abortion.

  9. 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.

  10. Gas exchange and the coagulation system of the blood during the effect on the body of high concentrations of oxygen and carbon dioxide

    Science.gov (United States)

    Palosh, L.; Agadzhanyan, N. A.; Davydov, G. A.; Rybakov, B. K.; Sergiyenko, A. S.

    1974-01-01

    Maximum permissible concentrations of oxygen and carbon dioxide in a controlled atmosphere were determined by evaluating their effects on human gas exchange, blood coagulation, and tolerances to acute hypoxia, acceleration, and physical loads. It was found that functional disturbances depend on the concentration of respiratory gases and the length of stay in an altered atmosphere. By changing the atmospheric composition and by bringing the gaseous environment into accordance with the work and rest regimen and energy expenditures, the general reactivity of the body changes favorably.

  11. Transforming the treatment for hemophilia B patients: update on the clinical development of recombinant fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP).

    Science.gov (United States)

    Santagostino, Elena

    2016-05-01

    Recombinant fusion protein linking recombinant coagulation factor IX with recombinant albumin (rIX-FP; Idelvion®(†)) is an innovative new treatment designed to extend the half-life of factor IX (FIX) and ease the burden of care for hemophilia B patients. The rIX-FP clinical development program - PROLONG-9FP - is in its advanced phases, with pivotal studies in previously treated adults, adolescents, and pediatrics now completed. Across all age groups studied, rIX-FP has demonstrated a markedly improved pharmacokinetic profile compared with plasma-derived and recombinant FIX treatments, with a 30-40% higher incremental recovery, an approximately 5-fold longer half-life, a lower clearance, and a greater area under the curve. rIX-FP has been very well tolerated with an excellent safety profile. In the pivotal studies, there have been no reports of FIX inhibitors or antidrug antibodies, and few treatment-related adverse events have been observed. Prophylactic regimens of rIX-FP administered once weekly to once every 14 days have been highly effective. When used for surgical prophylaxis, a single infusion of rIX-FP has been sufficient to maintain hemostasis, even during major orthopedic surgery. An ongoing study is now enrolling previously untreated patients and evaluating the possibility of extending the dosing interval to every 21 days. There is little doubt that rIX-FP will transform the treatment of hemophilia B. PMID:27288064

  12. Regulation of coagulation factor XI expression by microRNAs in the human liver.

    Directory of Open Access Journals (Sweden)

    Salam Salloum-Asfar

    Full Text Available High levels of factor XI (FXI increase the risk of thromboembolic disease. However, the genetic and environmental factors regulating FXI expression are still largely unknown. The aim of our study was to evaluate the regulation of FXI by microRNAs (miRNAs in the human liver. In silico prediction yielded four miRNA candidates that might regulate FXI expression. HepG2 cells were transfected with miR-181a-5p, miR-23a-3p, miR-16-5p and miR-195-5p. We used mir-494, which was not predicted to bind to F11, as a negative control. Only miR-181a-5p caused a significant decrease both in FXI protein and F11 mRNA levels. In addition, transfection with a miR-181a-5p inhibitor in PLC/PRF/5 hepatic cells increased both the levels of F11 mRNA and extracellular FXI. Luciferase assays in human colon cancer cells deficient for Dicer (HCT-DK demonstrated a direct interaction between miR-181a-5p and 3'untranslated region of F11. Additionally, F11 mRNA levels were inversely and significantly correlated with miR-181a-5p levels in 114 healthy livers, but not with miR-494. This study demonstrates that FXI expression is directly regulated by a specific miRNA, miR-181a-5p, in the human liver. Future studies are necessary to further investigate the potential consequences of miRNA dysregulation in pathologies involving FXI.

  13. Heparanase—A Link between Coagulation, Angiogenesis, and Cancer

    Directory of Open Access Journals (Sweden)

    Yona Nadir

    2012-01-01

    Full Text Available Heparanase that was cloned from and is abundant in the placenta is implicated in cell invasion, tumor metastasis, and angiogenesis. Recently we have demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. Heparanase was shown to up-regulate tissue factor (TF expression and interact with tissue factor pathway inhibitor (TFPI on the cell surface, leading to dissociation of TFPI from the cell membrane of endothelial and tumor cells, resulting in increased cell surface coagulation activity. More recently, we have shown that heparanase directly enhances TF activity, resulting in increased factor Xa production and activation of the coagulation system. Data indicate increased levels and possible involvement of heparanase in vascular complications in pregnancy. Taking into account the prometastatic and proangiogenic functions of heparanase, overexpression in human malignancies, and abundance in platelets and placenta, its involvement in the coagulation machinery is an intriguing novel arena for further research.

  14. Disseminated intravascular coagulation in burn injury.

    Science.gov (United States)

    Lippi, Giuseppe; Ippolito, Luigi; Cervellin, Gianfranco

    2010-06-01

    Disseminated intravascular coagulation (DIC) is a complex and multifaceted disorder characterized by the activation of coagulation and fibrinolytic pathways, consumption of coagulation factors, and depletion of coagulation regulatory proteins. The introduction into the circulation of cellular debris characterized by strong thromboplastic activity due to tissue factor exposition or release (in or from burned tissues), which can thereby activate extrinsic pathway of coagulation system and trigger massive thrombin generation when present in sufficient concentration, represents the most plausible biological explanation to support the development of intravascular coagulation in patients with burn injury. Severe burns left untreated might also lead to an immunological and inflammatory response (activation of the complement cascade), which can amplify fibrinolysis and blood clotting. Overall, the real prevalence of DIC in patients with burns is as yet unclear. Postmortem, retrospective, and even longitudinal investigations are in fact biased by several factors, such as the objective difficulty to establish whether DIC might have occurred as a primary complication of burns or rather as a consequence of other superimposed pathologies (e.g., sepsis, multiple organ failure), the different diagnostic criteria for assessing DIC, and the heterogeneity of the patient samples studied. Nevertheless, the current scientific evidence is consistent with the hypothesis that biochemical changes suggestive for DIC (hypercoagulability, hypo- and hyperfibrinolysis) are commonplace in patients with burn trauma, and their severity increases exponentially with the severity of injury. Overt DIC seems to occur especially in critically ill burn patients or in those with severe burns (up to third degree) and large involvement of body surface area, in whom an appropriate therapy might be effective to prevent the otherwise fulminant course. Although early prophylaxis with antithrombin concentrates

  15. The Ozagrel Influence of Sodium Combined Low Molecular Heparin Calcium’s Treatment on Transi-ent Ischemic Attack to ET-1 and Whole Blood Tissue Factor Coagulant Activity%奥扎格雷钠联合低分子肝素钙对短暂性脑缺血发作的疗效及内皮素和组织因子促凝活性的影响

    Institute of Scientific and Technical Information of China (English)

    郭梅; 雷蕾; 潘国雄; 赵瑛; 易蕾; 陈琦

    2014-01-01

    目的:回顾性分析奥扎格雷钠联合低分子肝素钙对短暂性脑缺血发作(TIA)患者血浆内皮素-1(ET-1)及全血组织因子促凝活性(TF-PCA)的影响。方法:选取108例经临床确诊的TIA患者,按随机数字表法分为奥扎格雷钠联合低分子肝素钙治疗组(观察组,n=54)和低分子肝素钙治疗对照组(治疗组,n=54),两组均给予降压、降脂、控制血糖等常规措施,另选同期体检健康者为对照组(n=56)。1个疗程后(7天)观察两组TIA患者临床疗效及不良反应,并分析治疗前后两组血浆 ET-1及全血TF-PCA水平变化。结果:观察组的治愈率和总有效率均明显高于治疗组(70.37% vs 46.30%,94.44% vs 72.22%,P 均<0.05)。治疗前,两组 TIA 患者 ET-1及 TF-PCA水平无明显差异,但均显著高于对照组(P<0.01);治疗后,两组患者 ET-1及 TF-PCA 均较治疗前明显降低(P<0.01),观察组较治疗组降低更明显(P<0.05)。治疗期间两组均未发生脑及其它脏器出血。结论:奥扎格雷钠联合低分子肝素钙治疗TIA效果良好,且无不良反应。%Objective:Through the observation of the ozagrel influence of sodium combined low molecular heparin calcium’s treatment on transient ischemic attack(TIA)to ET-1 and whole blood tissue factor coagulant ac-tivity.Method:108 cases of clinically diagnosed patients with TIA were divided into two groups randomly according to table method.One was ozagrel sodium combined low molecular heparin calcium treatment group (combination group,n=54),and the other one was low molecular heparin calcium treatment group (treatment group,n=54). Two groups were given conventional measures such as antihypertensive lipid control blood sugar.At the same time, choosed the healthy physical examination for the same period as the reference (normal control group,n=56).Plas-ma ET-1 and whole blood TF-PCA level before and after treatment were detected.Results:After ozagrel sodium combined low molecular heparin

  16. Fouling of microfiltration membranes by organic polymer coagulants and flocculants: controlling factors and mechanisms.

    Science.gov (United States)

    Wang, Sen; Liu, Charles; Li, Qilin

    2011-01-01

    Organic polymers are commonly used as coagulants or flocculants in pretreatment for microfiltration (MF). These high molecular weight compounds are potential membrane foulants when carried over to the MF filters. This study examined fouling of three MF membranes of different materials by three commonly used water treatment polymers: poly(diallyldimethylammonium) chloride (pDADMAC), polyacrylamide (PAM), and poly(acrylic acid-co-acrylamide (PACA) with a wide range of molecular weights. The effects of polymer molecular characteristics, membrane surface properties, solution condition and polymer concentration on membrane fouling were investigated. Results showed severe fouling of microfiltration membranes at very low polymer concentrations, suggesting that residual polymers carried over from the coagulation/flocculation basin can contribute significantly to membrane fouling. The interactions between polymers and membranes depended strongly on the molecular size and charge of the polymer. High molecular weight, positively charged polymers caused the greatest fouling. Blockage of membrane pore openings was identified as the main fouling mechanism with no detectable internal fouling in spite of the small molecular size of the polymers relative to the membrane pore size. Solution conditions (e.g., pH and calcium concentration) that led to larger polymer molecular or aggregate sizes resulted in greater fouling. PMID:20828779

  17. 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

    of the selective active site in defining specificity. Being a trypsin-like serine protease, FVIIa had P1 specificity exclusively towards arginine and lysine residues. In the S2 pocket, threonine, leucine, phenylalanine and valine residues were the most preferred amino acids. Both S3 and S4 appeared to be rather...... promiscuous, however, with some preference for aromatic amino acids at both positions. Interestingly, a significant degree of interdependence between the S3 and S4 was observed and, as a consequence, the optimal substrate for FVIIa could not be derived directly from a subsite-directed specificity screen...

  18. Novel role of antiplatelet agents (aspirin plus clopidogrel in an incoagulable blood of a victim of russell's viper snakebite

    Directory of Open Access Journals (Sweden)

    H. S. Bawaskar

    2006-01-01

    Full Text Available Snake antivenom is a specific antidote to the venom action, neutralizing the circulating venom. However, it fails to neutralize the venom fixed to target organs such as platelets, renal tubules, etc. Russell's viper venom initiates rapid coagulation in a victim by activating blood platelets, factors V, X, and anticoagulant cofactors. Activation of thrombin, resulting in formation of micro-thrombi, fibrinolysis, and a vicious cascade, sets in. Inhibition of activated platelets by aspirin (cyclooxygenase inhibitor and clopidogrel (ADP receptor inhibitor helps to break this vicious circle induced by Russell's venom and may initiate the natural physiological clotting mechanism. They can be utilized as an adjuvant treatment.

  19. Determination of coagulation inhibitor levels and resistance to activated protein C in patients undergoing gastric surgery for benign and malignant disorders

    DEFF Research Database (Denmark)

    Andersen, B S; Rahr, H B; Sørensen, J V

    1997-01-01

    The aim of the present study was to determine plasma levels of protein C antigen (PC:Ag) and activity (PC:Act), tissue factor pathway inhibitor (TFPI), protein S (PS), antithrombin (AT), heparin cofactor II (HCII), and resistance to activated protein C (APCR) before, during and after elective...

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

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    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.

  1. Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

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    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.

  2. Combined collision-induced dissociation and photo-selected reaction monitoring mass spectrometry modes for simultaneous analysis of coagulation factors and estrogens

    Directory of Open Access Journals (Sweden)

    Quentin Enjalbert

    2014-06-01

    Full Text Available Oral estrogens are directly associated with changes in plasma levels of coagulation proteins. Thus, the detection of any variation in protein concentrations due to estrogen contraceptives, by a simultaneous analysis of both coagulation proteins and estrogens, would be a very informative tool. In the present study, the merit of photo-selected reaction monitoring (SRM, a new analytical tool, was evaluated towards estrogens detection in plasma. Then, SRM and photo-SRM detection modes were combined for the simultaneous analysis of estrogen molecules together with heparin co-factor and factor XIIa, two proteins involved in the coagulation cascade. This study shows that photo-SRM could open new multiplexed analytical routes.

  3. Retention of coagulation factors in plasma frozen after extended holding at 1-6 degrees C

    NARCIS (Netherlands)

    Smith, JF; Ness, PM; Moroff, G; Luban, NLC

    2000-01-01

    Background and Objectives: The ability to use plasma, isolated from units of whole blood and frozen within 24 h of phlebotomy, as a substitute for plasma frozen within 8 h of phlebotomy would have several advantages for blood centers. It should provide increased flexibility pertaining to the freezin

  4. 常见影响凝血四项检测结果的因素%Common Factors affect the Test Results of Coagulation

    Institute of Scientific and Technical Information of China (English)

    金卫华

    2013-01-01

    Objective To observe the blood specimen col ection, transport, storage time on four items of blood coagulation determination were investigated. Methods: the prothrombin time for some this wil be found in the work of the common influencing factors (PT), fibrinogen (FIB), activated partial thromboplastin time (AFTT) and thrombin time (determination of TT). Results:the status of the instrument has a direct impact on the experimental results, the accuracy of operator's ability and the sense of responsibility for the result plays an important role. Conclusion:strict control of blood with anticoagulant ratio, avoid using glass tube, in pay at ention to every detail and at ention, to ensure the accuracy of test results, the reliability and authenticity.%目的:观察血液标本、采集、运送、放置时间对凝血四项测定结果的影响。方法本文将在工作中发现的一些常见影响因素进行凝血酶原时间(PT),纤维蛋白原(FIB),活化部分凝血活酶时间(AFTT)和凝血酶时间(TT)测定。结果仪器状态的好坏直接影响实验的结果,操作人员的能力及责任心对于结果的准确性起至关重要的作用。结论严格控制血液与抗凝剂比例,忌用玻璃管,检测中重视每一个细小环节并加以注意,才能保证检测结果的准确性、可靠性和真实性。

  5. Disseminated Intravascular Coagulation in Infectious Disease

    NARCIS (Netherlands)

    M. Levi; M. Schultz; T. van der Poll

    2010-01-01

    Severe infection and inflammation almost invariably lead to hemostatic abnormalities, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation. Systemic inflammation as a result of severe infection leads to activation of coagulation, due to tissue factor-mediate

  6. Observation in vitro of ulinastatin on human blood coagulation%乌司他丁对人凝血功能影响的体外观察

    Institute of Scientific and Technical Information of China (English)

    徐震; 王卓强; 刘秀珍; 张斌; 王恒林; 范里莉

    2009-01-01

    Objective To investigate the effects of ulinastatin on blood coagulation in vitro. Methods Ulinastatin was mixed with venous blood samples obtained from 16 healthy adult volunteers to reach the plasma concentration of 25U/ml, 50U/ml, 75U/ml,100U/ml and 200U/ml, respectively. Coagulation function was measured with Sonoclot coagulation and platelet function analyzer. The parameters measured included activated clotting time (ACT), clot rate (CR) and platelet function (PF). Blood sample without ulinastatin treatment was taken as control group. Results Compared with control value, no significant difference of ACT was observed in 25U/ml, 50U/ml and 75U/ml of ulinastatin treated groups (P>0. 05), while in 100U/ml and 200U/ml groups, ACT was significantly prolonged (P0. 05). Similarly, PF in 25U/ml and 50U/ml groups showed no significant difference compared with that in control group (P>0.05) , while in 75U/ml,100U/ml and 200U/ml groups, PF decreased significantly (P0.05),而:100、200U/ml组ACT较对照组显著延长(.P0.05);25、50tJ/ml组PF与对照组比较无显著差异(P>0.05),而75、100、200[J/IIll组PF均显著低于对照组(P<0.05).结论 乌司他丁在全血中的浓度达到100[J/rnl以上时,能有效地延迟内源性凝血通路的活化,并在一定程度上抑制血小板功能,从而延缓病理性凝血过程的出现,改善大型手术围术期凝血功能.

  7. Severe coagulation factor VII deficiency caused by a novel homozygous mutation (p. Trp284Gly) in loop 140s.

    Science.gov (United States)

    Hao, Xiuping; Cheng, XiaoLi; Ye, Jiajia; Wang, Yingyu; Yang, LiHong; Wang, Mingshan; Jin, Yanhui

    2016-06-01

    Congenital coagulation factor VII (FVII) deficiency is a rare disorder caused by mutation in F7 gene. Herein, we reported a patient who had unexplained hematuria and vertigo with consanguineous parents. He has been diagnosed as having FVII deficiency based on the results of reduced FVII activity (2.0%) and antigen (12.8%). The thrombin generation tests verified that the proband has obstacles in producing thrombin. Direct sequencing analysis revealed a novel homozygous missense mutation p.Trp284Gly. Also noteworthy is the fact that the mutational residue belongs to structurally conserved loop 140s, which majorly undergo rearrangement after FVII activation. Model analysis indicated that the substitution disrupts these native hydrophobic interactions, which are of great importance to the conformation in the activation domain of FVIIa. PMID:26761581

  8. Relationship between coagulation factors and urticaria%凝血因子与荨麻疹的关系

    Institute of Scientific and Technical Information of China (English)

    梁碧华; 朱慧兰

    2009-01-01

    荨麻疹是一种常见的、复发性的皮肤病.其发病机制复杂,至今尚未完全清楚.近年来有学者提出荨麻疹发病可能与凝血状态有关,并对凝血酶原片段F1+2、D二聚体、因子Ⅶ和因子Ⅻ等凝血因子进行相关研究,认为慢性荨麻疹患者体内存在外源性凝血级联反应激活以及纤溶状态,凝血酶生成可能在荨麻疹的发病中起着作用.抗凝治疗在荨麻疹药物治疗中显示出一定的临床应用前景.%Urticaria is a common, recurrent and refractory skin disease. The exact pathogenic mechanism of urticaria is complex and unclear. It has been proposed that the development of urticaria is associated with coagulation status. Related studies on thrombinogen fragment F (1+2), D dimmer, factor Ⅶ and factor Ⅻ revealed the activation of extrinsic pathway of coagulation cascade and signs of fibrinolysis in patients with chronic urticaria. Thromhin generation may play a key role in the pathogenesis of urticaria. And anticoagulant drugs have exhibited a good prospect in the medication of urticaria.

  9. 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.

  10. Establishment of FMEA risk management procedures for blood coagulation tests in clinical laboratories%临床实验室按照 FM EA 模式构建凝血功能检测项目的风险管理程序

    Institute of Scientific and Technical Information of China (English)

    牛广华; 高玉洁; 崔百慧

    2016-01-01

    使用FMEA模型确定检验医学中心风险管理工作流程和关键环节。根据IS015189认可准则、CAP实验室认可检查条款等的相关标准,识别出实验室凝血功能检测工作流程中关键环节的风险。针对凝血功能检测的评价活动,采取积极的纠正措施,通过监测系统周期性地审核性能数据,可以对凝血功能检测的质量持续改进。(中华检验医学杂志,2016,39:13-17)%Definiting the workflow and key link of the risk management in medical laboratory by FMEA.Identifying risk factors of the workflow and key link of blood coagulation test by the criteria for laboratory accreditation , such as ISO15189 recognition criteria and CAP laboratory accreditation inspection . Through the evaluation of the blood coagulation test , effective corrective actions and examining performance data periodically , the quality of the blood coagulation test can be improved continuously.

  11. Effects on coagulation and fibrinolysis induced by influenza in mice with a reduced capacity to generate activated protein C and a deficiency in plasminogen activator inhibitor type 1

    NARCIS (Netherlands)

    T.T. Keller; K.F. van der Sluijs; M.D. de Kruif; V.E.A. Gerdes; J.C.M. Meijers; S. Florquin; T. van der Poll; E.C.M. van Gorp; D.P.M. Brandjes; H.R. Buller; M. Levi

    2006-01-01

    Influenza infections increase the risk of diseases associated with a prothrombotic state, such as venous thrombosis and atherothrombotic diseases. However, it is unclear whether influenza leads to a prothrombotic state in vivo. To determine whether influenza activates coagulation, we measured coagul

  12. Extrahepatic sources of factor VIII potentially contribute to the coagulation cascade correcting the bleeding phenotype of mice with hemophilia A.

    Science.gov (United States)

    Zanolini, Diego; Merlin, Simone; Feola, Maria; Ranaldo, Gabriella; Amoruso, Angela; Gaidano, Gianluca; Zaffaroni, Mauro; Ferrero, Alessandro; Brunelleschi, Sandra; Valente, Guido; Gupta, Sanjeev; Prat, Maria; Follenzi, Antonia

    2015-07-01

    A large fraction of factor VIII in blood originates from liver sinusoidal endothelial cells although extrahepatic sources also contribute to plasma factor VIII levels. Identification of cell-types other than endothelial cells with the capacity to synthesize and release factor VIII will be helpful for therapeutic approaches in hemophilia A. Recent cell therapy and bone marrow transplantation studies indicated that Küpffer cells, monocytes and mesenchymal stromal cells could synthesize factor VIII in sufficient amount to ameliorate the bleeding phenotype in hemophilic mice. To further establish the role of blood cells in expressing factor VIII, we studied various types of mouse and human hematopoietic cells. We identified factor VIII in cells isolated from peripheral and cord blood, as well as bone marrow. Co-staining for cell type-specific markers verified that factor VIII was expressed in monocytes, macrophages and megakaryocytes. We additionally verified that factor VIII was expressed in liver sinusoidal endothelial cells and endothelial cells elsewhere, e.g., in the spleen, lungs and kidneys. Factor VIII was well expressed in sinusoidal endothelial cells and Küpffer cells isolated from human liver, whereas by comparison isolated human hepatocytes expressed factor VIII at very low levels. After transplantation of CD34(+) human cord blood cells into NOD/SCIDγNull-hemophilia A mice, fluorescence activated cell sorting of peripheral blood showed >40% donor cells engrafted in the majority of mice. In these animals, plasma factor VIII activity 12 weeks after cell transplantation was up to 5% and nine of 12 mice survived after a tail clip-assay. In conclusion, hematopoietic cells, in addition to endothelial cells, express and secrete factor VIII: this information should offer further opportunities for understanding mechanisms of factor VIII synthesis and replenishment.

  13. Extrahepatic sources of factor VIII potentially contribute to the coagulation cascade correcting the bleeding phenotype of mice with hemophilia A.

    Science.gov (United States)

    Zanolini, Diego; Merlin, Simone; Feola, Maria; Ranaldo, Gabriella; Amoruso, Angela; Gaidano, Gianluca; Zaffaroni, Mauro; Ferrero, Alessandro; Brunelleschi, Sandra; Valente, Guido; Gupta, Sanjeev; Prat, Maria; Follenzi, Antonia

    2015-07-01

    A large fraction of factor VIII in blood originates from liver sinusoidal endothelial cells although extrahepatic sources also contribute to plasma factor VIII levels. Identification of cell-types other than endothelial cells with the capacity to synthesize and release factor VIII will be helpful for therapeutic approaches in hemophilia A. Recent cell therapy and bone marrow transplantation studies indicated that Küpffer cells, monocytes and mesenchymal stromal cells could synthesize factor VIII in sufficient amount to ameliorate the bleeding phenotype in hemophilic mice. To further establish the role of blood cells in expressing factor VIII, we studied various types of mouse and human hematopoietic cells. We identified factor VIII in cells isolated from peripheral and cord blood, as well as bone marrow. Co-staining for cell type-specific markers verified that factor VIII was expressed in monocytes, macrophages and megakaryocytes. We additionally verified that factor VIII was expressed in liver sinusoidal endothelial cells and endothelial cells elsewhere, e.g., in the spleen, lungs and kidneys. Factor VIII was well expressed in sinusoidal endothelial cells and Küpffer cells isolated from human liver, whereas by comparison isolated human hepatocytes expressed factor VIII at very low levels. After transplantation of CD34(+) human cord blood cells into NOD/SCIDγNull-hemophilia A mice, fluorescence activated cell sorting of peripheral blood showed >40% donor cells engrafted in the majority of mice. In these animals, plasma factor VIII activity 12 weeks after cell transplantation was up to 5% and nine of 12 mice survived after a tail clip-assay. In conclusion, hematopoietic cells, in addition to endothelial cells, express and secrete factor VIII: this information should offer further opportunities for understanding mechanisms of factor VIII synthesis and replenishment. PMID:25911555

  14. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial.

    Science.gov (United States)

    Santagostino, Elena; Martinowitz, Uri; Lissitchkov, Toshko; Pan-Petesch, Brigitte; Hanabusa, Hideji; Oldenburg, Johannes; Boggio, Lisa; Negrier, Claude; Pabinger, Ingrid; von Depka Prondzinski, Mario; Altisent, Carmen; Castaman, Giancarlo; Yamamoto, Koji; Álvarez-Roman, Maria-Teresa; Voigt, Christine; Blackman, Nicole; Jacobs, Iris

    2016-04-01

    A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P< .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered atwww.clinicaltrials.govas #NCT0101496274. PMID:26755710

  15. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial

    Science.gov (United States)

    Martinowitz, Uri; Lissitchkov, Toshko; Pan-Petesch, Brigitte; Hanabusa, Hideji; Oldenburg, Johannes; Boggio, Lisa; Negrier, Claude; Pabinger, Ingrid; von Depka Prondzinski, Mario; Altisent, Carmen; Castaman, Giancarlo; Yamamoto, Koji; Álvarez-Roman, Maria-Teresa; Voigt, Christine; Blackman, Nicole; Jacobs, Iris

    2016-01-01

    A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P < .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered at www.clinicaltrials.gov as #NCT0101496274. PMID:26755710

  16. Optical factors determined by the T-matrix method in turbidity measurement of absolute coagulation rate constants.

    Science.gov (United States)

    Xu, Shenghua; Liu, Jie; Sun, Zhiwei

    2006-12-01

    Turbidity measurement for the absolute coagulation rate constants of suspensions has been extensively adopted because of its simplicity and easy implementation. A key factor in deriving the rate constant from experimental data is how to theoretically evaluate the so-called optical factor involved in calculating the extinction cross section of doublets formed during aggregation. In a previous paper, we have shown that compared with other theoretical approaches, the T-matrix method provides a robust solution to this problem and is effective in extending the applicability range of the turbidity methodology, as well as increasing measurement accuracy. This paper will provide a more comprehensive discussion of the physical insight for using the T-matrix method in turbidity measurement and associated technical details. In particular, the importance of ensuring the correct value for the refractive indices for colloidal particles and the surrounding medium used in the calculation is addressed, because the indices generally vary with the wavelength of the incident light. The comparison of calculated results with experiments shows that the T-matrix method can correctly calculate optical factors even for large particles, whereas other existing theories cannot. In addition, the data of the optical factor calculated by the T-matrix method for a range of particle radii and incident light wavelengths are listed.

  17. Thromboelastometry (TEM) findings in disseminated intravascular coagulation in a pig model of endotoxinemia.

    Science.gov (United States)

    Schöchl, Herbert; Solomon, Cristina; Schulz, Arthur; Voelckel, Wolfgang; Hanke, Alexander; Van Griensven, Martijn; Redl, Heinz; Bahrami, Soheyl

    2011-01-01

    Standard coagulation tests have a low specificity and sensitivity for diagnosing disseminated intravascular coagulation. The aim of this study was to determine whether whole blood thromboelastometry (TEM) detects lipopolysaccharide (LPS)-induced changes in coagulation. Blood samples from 10 pigs were drawn at baseline, before and at the end of LPS infusion and 2, 3, 4 and 5 h after the start of endotoxinemia. Simultaneous to TEM, standard coagulation tests and extended coagulation analysis including tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) were performed. Endotoxinemia resulted in a significant acceleration of the nonactivated TEM (NATEM) clotting time 2 h after the end of LPS infusion; in contrast, the changes in international normalized ratio and activated partial thromboplastin time suggested delayed initiation of coagulation. NATEM maximum clot firmness (MCF) and fibrin-based thromboelastometry test (FIBTEM)-MCF decreased significantly from baseline until the last time point (from 64.6 ± 7.8 and 35.1 ± 12.8 mm to 52.8 ± 4.6 and 21.4 ± 11.8 mm, respectively; P = 0.01 for both parameters). A sharp, transient increase of t-PA had no effect on maximum lysis in the NATEM test. PAI-1 increased significantly 3 h after the start of LPS infusion, paralleled by a decrease in maximum lysis. In conclusion, TEM was superior to standard coagulation tests in reflecting initial activation of coagulation during endotoxinemia. TEM further suggested consumption of coagulation substrate; at the same time, inhibition of plasminogen activation was accompanied by improved clot stability. Further investigations are necessary to establish the clinical relevance of these findings.

  18. 不同全自动凝血仪检测结果的分析研究%Comparative Analysis of Results with Different Automatic Blood Coagulation Analyzers

    Institute of Scientific and Technical Information of China (English)

    李玲; 刘文康; 詹颉; 解娟; 李博; 任健康

    2012-01-01

    目的:探讨不同全自动凝血分析仪检测结果是否具有可比性,同时对其检测结果临床可接受性进行评估,使不同全自动凝血分析仪检测结果标准化.方法:连续30天用SYSMEX CA- 1500及CA-7000全自动凝血分析仪同时检测并比对仪器配套定值质控物的PT、INR、APTT、FIB、TT值;同时连续30天利用两台仪器检测并对比新鲜血标本的PT、INR、APTT、FIB、TT值.结果:SYSMEX CA- 1500及CA-7000日间质控物各检测项目:PT、INR、APTT、FIB、TT变异系数均小于5%.CA- 1500及CA-7000全自动凝血分析仪检测新鲜血标本:PT、INR、APTT、FIB、TT统计分析结果,t检验其P值均>0.05;相关系数r在0.993-0.999之间;两台仪器的偏差均符合1/2美国CLIA’88能力验证分析质量要求.结论:两台仪器PT、INR、APTT、FIB、TT的检测结果具有很好的相关性,经统计分析两台仪器检测结果无统计学意义.对不同凝血分析仪进行比对分析,不仅能够及时发现仪器存在的系统误差.而且使其检测结果具有很好的一致性,给临床可提供一个准确、可靠一致的实验室检测结果,使临床对疾病的诊断、疗效观察有一个统一的评判标准.%Objective: The purpose of our study was to analyze results comparability with different automatic blood coagulation analyzers and to estimate clinical acceptability in order to standardize the results with different automatic blood coagulation analyzers. Methods:The values of PT, INR, APTT, FIB and TT were obtained and compared in fresh blood samples and quality controls with instrument matching definite values with SYSMEX CA-1500 and CA-7000 analyzers for 30 days continuously. Results: The coefficient of variations of values of PT, INR, APTT, FIB and TT in inter-day quality controls with SYSMEX CA-1500 and CA-7000 were all less than 5%. Statistical analysis on values of PT, INR, APTT, FIB and TT in fresh blood samples with CA-1500 and CA-7000 analyzers

  19. A comparative study of the effect of continuous combined conjugated equine estrogen plus medroxyprogesterone acetate and tibolone on blood coagulability

    DEFF Research Database (Denmark)

    Skouby, SO; Sidelmann, JJ; Nilas, Lisbeth;

    2007-01-01

    : Thirty-eight post-menopausal women were randomly assigned to 1.25 or 2.5 mg per day of tibolone or oral continuous combined conjugated equine estrogen plus medroxyprogesterone acetate (CEE/MPA). Inhibitors of haemostasis were measured at baseline and after 12 months. RESULTS: Results from the two groups...

  20. [MORPHOFUNCTIONAL STATE OF BLOOD CELLS AFTER CHRONIC EXPOSURE OF THE PROTEIN KINASES INHIBITOR MALEIMIDE DERIVATIVE].

    Science.gov (United States)

    Byelinska, I V; Lynchak, O V; Tsyvinska, S M; Rybalchenko, V K

    2015-01-01

    The effect of the protein kinases inhibitor maleimide derivative (MI-1, 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione), inhibitor of VEGF-R1,2,3, FGF-R1, EGF-R(h), PDK1, Src(h), Syk(h), YES, ZAP70 et al. with antineoplastic activity, on blood cells parameters of rats after chronic exposure has been studied. Administration of MI-1 at doses 0.027 and 2.7 mg/kg (suppress colon carcinogenesis) for 20 and 26 weeks does not affect the morphofunctional state of red blood cells in healthy rats. This is confirmed by the lack of differences in the concentration of hemoglobin in blood, red blood cells count, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, hematocrit and mean corpuscular volume, and the number of reticulocytes in blood after 20 and 26 weeks of exposure compared with the control group. MI-1 at indicated doses does not influence total leukocytes count and content (eosinophilic and neutrophilic granulocytes, lymphocytes, monocytes) and does not inhibit thrombocytopoiesis (platelet count remains unchanged). No negative effect of MI-1 on hematopoiesis is not limited (by the hemopoietic system) use of this compound as a potential antitumor drug PMID:26552308

  1. In vitro inhibitory effect of papain on blood coagulation function and the related mechanism%木瓜蛋白酶对凝血功能的抑制作用及机制的体外研究

    Institute of Scientific and Technical Information of China (English)

    徐伟红; 吕远栋; 陶萍华; 吴国友; 俞蔚; 胡细连

    2013-01-01

    目的:观察木瓜蛋白酶体外对凝血功能的抑制作用,并探讨其可能机制.方法:将不同剂量木瓜蛋白酶分别与贫血小板血浆(PPP)和富血小板血浆(PRP)作用,分为生理盐水组、10 U/L组和20 U/L组,分别以血凝仪测定PPP和PRP的凝血酶原时间(PT)和活化部分凝血活酶时间(APTT),以血气分析仪和血凝仪分别测定PPP的Ca2+浓度和凝血因子Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅸ和Ⅺ活性(FV:C、FⅦ:C、FⅧ:C、FⅨ:C、FⅩ:C和FⅪ:C);将新鲜全血与前述3种浓度木瓜蛋白酶作用,采用硅化管法测定全血凝血时间(CT).同时测定0、20、40、60和80 U/L木瓜蛋白酶PPP的PT和APTT值.结果:10 U/L和20 U/L木瓜蛋白酶组PPP和PRP的PT和APTT值、全血CT值分别显著高于生理盐水组和10 U/L木瓜酶组(P<0.01),FⅤ:C和FⅧ:C水平分别显著低于生理盐水组和10 U/L木瓜酶组(P<0.05);三组PPP与PRP之间PT和APTT值、各组间Ca2+浓度以及其余凝血因子活性差异均无显统计学意义(P>0.05).PPP的PT和APTT值均与木瓜蛋白酶剂量呈显著正相关(r=0.995和0.991,P<0.01).结论:木瓜蛋白酶可通过抑制凝血因子Ⅴ和Ⅷ活性,从而对凝血功能有剂量依赖性的抑制作用,具有抗凝的功效.%AIM: To observe the in vitro effect of papain on blood coagulation function, and to explore the possible mechanism.METH ODS: Human platelet poor plasma (PPP) and platelet rich plasma (PRP) were mixed with dif ferent dose of papain which were assigned into three groups (group 0 U/L, group 10 U/L and group 20 U/L).PPP and PRP were measured for prothrombin time(PT) and actvated partial thromboplastin time (APTT) with blood coagu lation analyzer, the PPP was also measured for Ca2+ and activity of coagulable factor V, VII, VIII, IX, X and XI(FV:C、FVII:C、FVIII:C、 FIX:C、FX:C and FXI:C) with blood-gas analy zer and blood coagulation analyzer, respectively.Fresh blood from volunteers was mixed with the three dose of papain

  2. Risk Factors of Viral Hepatitis B among Egyptian Blood Donors

    OpenAIRE

    Awadalla, HI; Ragab, MH; Osman, MA; Nassar, NA; Cairo, Egypt.

    2011-01-01

    Background: Surveillance of infectious disease markers in the blood donor population is important in recognizing trends in prevalence and incidence of transfusion related infections in asymptomatic volunteer blood donors. Subjects & Methods: It is a community base cross sectional study. Subjects of study are volunteers to donate blood. Samples were collected from blood donors and questionnaire was designed to collect the risk factors data. The prevalence of hepatitis B surface antigen (HB...

  3. Usefulness of circulating vascular endothelial growth factor and neutrophil elastase as diagnostic markers of disseminated intravascular coagulation in non-cancer patients

    OpenAIRE

    Joo, Shin Young; Kim, Ji-Eun; Kim, Ju Young; Han, Kyou-Sup; Kim, Hyun Kyung

    2010-01-01

    Background Disseminated intravascular coagulation (DIC) is characterized by platelet and neutrophil activation. Platelets are the major source of circulating vascular endothelial growth factor (VEGF). Endostatin, an anti-angiogenic factor, is a fragment of collagen that is released from the extracellular matrix via the active cleavage of neutrophil elastase, thereby increasing the circulating level of endostatin. Hypercoagulable conditions such as DIC may induce the release of VEGF and neutro...

  4. Characteristics of blood donors and factors associated with blood donation in Guangzhou

    OpenAIRE

    Ouyang, Jian; 欧阳剑

    2013-01-01

    Objective: To describe and compare the characteristics of blood donors and non-donors and to examine factors associated with donation, including motivators and barriers of blood donation in Guangzhou, China. Design: Cross-sectional survey using self-administered standardized structured questionnaires on both donors and non-donors. Setting: 12 mobile and 4 permanent blood donation stations in Guangzhou during the whole operation time. Participants: 500 blood donors who donated at th...

  5. [ABO BLOOD GROUPS AS RISK FACTOR IN HELICOBACTER PYLORI INFECTION

    Science.gov (United States)

    Gonzáles Flores, Pedro Alejandro; Díaz Ferrer, Javier Omar; Monge Salgado, Eduardo; Watanabe Varas T, Teresa

    2000-01-01

    TITLE: ABO blood groups as risk factor in Helicobacter pylori infection.OBJECTIVE: To asses the relation between ABO blood groups and Helicobacter pylori (Hp) infection. METHODS: The present is a case and control study. A study population of dyspeptic patients who underwent upper gastrointestinal endoscopy was selected. Four biopsies were taken from the antrum and the body of the stomach and blood group was typified. Patients with gastrectomy, gastric cancer, treated for Hp infection in the previous six months or without blood group typification were excluded. The population sample was found using EPIINFO 5.1 program. We called case to every patient with Hp (+) biopsy and control all with Hp (-) biopsy. The risk of the infection was calculated with the OR (Odds ratio) and the study sample was compared with the blood bank control group using the Chi-square test (pblood groups between the study population and the blood bank control. When we compared the ABO blood distribution between patients Hp (+) and Hp (-) we found significant differences for blood group O (p=0.004) and blood group A (p=0.03). Statistical analysis revealed an OR=2,22 for the blood group O and OR=0,5 for the blood group A.CONCLUSIONS: 1) The ABO blood group distribution is different in patients with Hp infection compared with those without Hp infection. 2) Blood group O would be a moderate risk factor for infection by Helicobacter pylori. PMID:12140571

  6. Test and Analysis of Coagulation Time of Four Kinds of Coagulation Factors in Captive Bred Tree Shrew and Rhesus Monkey%人工饲养树鼩和猕猴的部分凝血因子凝集时间的测定及分析

    Institute of Scientific and Technical Information of China (English)

    黄璋琼; 代解杰; 孙晓梅; 李辛斌; 高家红

    2011-01-01

    Objective To test and analyze the coagulation time of four kinds of coagulation factors in healthy , captive bred tree shrew and rhesus monkey, and to establish the reference values range of coagulation factors values in the two animals. Methods Prothrombin time ( PT) , activated partial thromboplastin time ( APTT) , fibrinogen time ( FIB) , and thrombin time ( TT) of captive bred tree shrews and rhesus monkeys were tested by using the Sysmex CA-510 automated blood coagulation analyzer, then the data were analyzed in using the statistics analysis software SPSS vl7. 0. Results In Tree shrew and Rhesus monkey, TT was respectively 19. 27 s and 20. 81 s;PT was respectively 17.34 s and 9.82 s; FIB was respectively 30.51 s and 18.73s; APPT was respectively 27. 88 s and 33. 56 s. The differences in PT and FIB were highly significant(P <0. 01) between captive bred tree shrew and rhesus monkey;and the differences in TT and APTT were also statistical significant(P <0. 05) between the captive bred tree shrew and the rhesus monkey. Conclusion There were significant differences in coagulation time of the four kinds of coagulation factors between animals, but there had no differencees in the different gender of same species.%目的 目前有关人工饲养树鼩与猕猴部分凝血因子凝集时间的资料甚少,拟初步建立这两种动物部分凝血因子凝集时间的参考值范围.方法采用全自动血凝仪测定树鼩、猕猴的血浆凝血酶时间(TT)、纤维蛋白原(Fib)、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT).结果树鼩的TT、PT、Fib和APTT值分别为19.27、17.34、30.51和27.88s.猕猴的TT、PT、Fib和APTT值分别为20.81、9.82、18.73和33.56 s.人工饲养树鼩与猕猴的PT值、Fib值存在显著性差异(P<0.01),APTT值、TT值存在差异(P<0.05).结论人工饲养树鼩和猕猴部分凝血因子的凝集时间存在一定差异,同一物种雌雄个体间部分凝血因子的凝集时间没有明显差异.

  7. Momordica charantia seed extract exhibits strong anticoagulant effect by specifically interfering in intrinsic pathway of blood coagulation and dissolves fibrin clot.

    Science.gov (United States)

    Manjappa, Bhagyalakshmi; Gangaraju, Sowmyashree; Girish, Kesturu S; Kemparaju, Kempaiah; Gonchigar, Sathish J; Shankar, Rohit L; Shinde, Manohar; Sannaningaiah, Devaraja

    2015-03-01

    The current study explores the anticoagulant and fibrin clot-hydrolyzing properties of Momordica charantia seed extract (MCSE). MCSE hydrolyzed casein with the specific activity of 0.780 units/mg per min. Interestingly, it enhanced the clot formation process of citrated human plasma from control 146 to 432 s. In addition, the intravenous injection of MCSE significantly prolonged the bleeding time in a dose-dependent manner from control 150 to more than 800 s, and strengthened its anticoagulant activity. Interestingly, MCSE specifically prolonged the clotting time of only activated partial thromboplastin time, but not prothrombin time, and revealed the participation of MCSE in the intrinsic pathway of the blood coagulation cascade. Furthermore, MCSE completely hydrolyzed both Aα and Bβ chains of the human fibrinogen and partially hydrolyzed the γ chain. However, it hydrolyzed all the chains (α polymer, α chain, β chain and γ-γ dimmers) of partially cross-linked human fibrin clot. The proteolytic activity followed by the anticoagulant effect of the MCSE was completely abolished by the 1,10-phenanthroline and phenyl methyl sulphonyl fluoride, but iodoacetic acid, EDTA, and ethylene glycol-N,N,N',N'-tetra acetic acid did not. Curiously, MCSE did not hydrolyze any other plasma proteins except the plasma fibrinogen. Moreover, MCSE was devoid of RBC lysis, edema and hemorrhagic properties, suggesting its nontoxic nature. Taken together, MCSE may be a valuable candidate in the treatment of blood clot/thrombotic disorders. PMID:25192240

  8. 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

    plasma, in cold activated plasma and in FVII deficient plasma. There was a positive correlation (r=0.96) between FVII:Ag and FVII:Am with slightly but significantly higher values for FVII:Ag (FVII:Ag= 106 U/ml and FVII:Am=100 U/ml; p ... omitting the data from patients on oral anticoagulant therapy, with mean values of 113 U/ml for FVII:Ag and 110 U/ml for FVII:Am (p

  9. Coagulation and Fibrinolysis Indicators and Placental Malaria Infection in an Area Characterized by Unstable Malaria Transmission in Central Sudan

    Directory of Open Access Journals (Sweden)

    Amged G. Mostafa

    2015-01-01

    Full Text Available This study aimed to investigate coagulation, fibrinolysis indicators, and malaria during pregnancy. Methods. A cross-sectional study was conducted at Medani, Sudan. Sociodemographic characteristics were gathered from each parturient woman (163 and malaria was investigated by blood film and placental histology. Protein C, protein S, antithrombin-III, tissue factor pathway inhibitor (TFPI, and plasminogen activator inhibitor-1 levels (PAI-1 were measured using ELISA. Results. One (0.6%, three (1.8, and 19 (11.7% of the placentae showed active, chronic, and past infection on a histopathological examination, respectively, while 140 (85.9% of them showed no signs of malaria infection. While the mean [SD] of the protein C, antithrombin-III, and TFPI was significantly lower, there was no significant difference in protein S and PAI-1 levels in women with placental malaria infection (n=23 compared to those without placental malaria infection (140. In linear regression, placental malaria infection was associated with antithrombin-III. There was no association between placental malaria infections and protein C, protein S, TFPI, and PAI-1 levels. There was no association between hemoglobin, birth weight, and the investigated coagulation and fibrinolysis indicators. Conclusion. This study showed significantly lower levels of protein C, antithrombin-III, and TFPI in women with placental malaria infections.

  10. Phase III study on surface construction and biocompatibility of polymer materials as cardiovascular devices:coagulant and anti-coagulant surface modification

    Institute of Scientific and Technical Information of China (English)

    Chen Bao-lin; Wang Dong-an

    2015-01-01

    BACKGROUND: As the cardiovascular device, biomaterials applied under the blood-contact conditions should have anti-thrombotic, anti-biodegradable and anti-infective properties. OBJECTIVE: To develop novel polymer materials for implantation and intervention in cardiovascular tissue engineering and to explore the biocompatibility, blood compatibility and cytocompatibility of the surface-modified polymer biomaterials based on the coagulant and anti-coagulant coating modification. METHODS:We retrieved PubMed and WanFang databases for relevant articles publishing from 1983 to 2014. The key words were "biocompatibility, blood compatibility, biomedical materials, biomedical polymer materials" in English and Chinese, respectively. Those unrelated, outdated and repetitive papers were excluded. Literatures addressing the blood compatibility of biomedical polymer materials were summarized. RESULTS AND CONCLUSION: The blood-implant interaction and the anti-coagulant surface modification of biomaterials were analyzed. The biocompatibility, blood compatibility and cytocompatibility of the surface-modified polymer biomaterials were determined based on the coagulant and anti-coagulant coating modification. The coagulant and anti-coagulant surface modification of polymer biomaterials and the research on their biocompatibility and endothelial cel compatibility are crucial for developing novel polymer materials for implantation and intervention in cardiovascular tissue engineering. Through in-depth studies of the types and applications of polymer biomaterials, cardiovascular medical devices and implantable soft tissue substitutes, the differences between the surface and the body wil be reflected in the many layers of molecules extending from the surface to the body. Two major factors, surface energy and molecular mobility, determine the body/surface behaviors that include body/surface differences and phase separation. Considering the difference between the body/surface composition

  11. Motivating Factors and Potential Deterrents to Blood Donation in High School Aged Blood Donors

    OpenAIRE

    Rachel Finck; Alyssa Ziman; Matthew Hoffman; Michelle Phan-Tang; Shan Yuan

    2016-01-01

    Background. To ensure an adequate supply of blood, collection centers must design campaigns that successfully recruit and maintain an active donor pool. Understanding factors that motivate and deter individuals from donating may help centers develop targeted recruitment campaigns. These factors among high school aged blood donors have not yet been fully investigated. Study Design and Methods. A voluntary, anonymous survey was administered to student donors at high school mobile blood drives. ...

  12. Correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2

    Institute of Scientific and Technical Information of China (English)

    ZHOU Shao-fei; HU San-yuan; MA Lei; MIAO Lei; MAO Wei-zheng

    2013-01-01

    Background The relationship between the presence of metalloproteinases and thyroid cancer remains unknown,and many controversies still exist in this field.The objective of this study was to investigate the correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2,matrix metalloproteinase-9,tissue inhibitor of metalloproteinase-1,and tissue inhibitor of metalloproteinase-2.Methods The correlations were studied by detecting the levels of matrix metalloproteinase-2,matrix metalloproteinase-9,tissue inhibitor of metalloproteinase-1,and tissue inhibitor of metalloproteinase-2 by enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the peripheral blood of 30 patients with papillary thyroid carcinoma,27 patients with benign thyroid disease,and 25 healthy volunteers.Results The levels of matrix metalloproteinase-2,matrix metalloproteinase-9,tissue inhibitor of metalloproteinase-1,and tissue inhibitor of metalloproteinase-2 in the peripheral blood of patients with papillary thyroid carcinoma were significantly higher than those in the peripheral blood of patients with benign thyroid disease and healthy volunteers (P <0.05).However,there were no significant differences between patients with benign thyroid disease and healthy volunteers (P >0.05).The accuracy of detection by both enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the papillary thyroid cancer group was 83.33%.Conclusions The levels of matrix metalloproteinase-2,matrix metalloproteinase-9,tissue inhibitor of metalloproteinase-1,and tissue inhibitor of metalloproteinase-2 in the peripheral blood are helpful in identifying thyroid carcinoma and aid in preoperative assessment.

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

    International Nuclear Information System (INIS)

    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)

  14. Aggressive Periodontitis and Chronic Arthritis: Blood Mononuclear Cell Gene Expression and Plasma Protein Levels of Cytokines and Cytokine Inhibitors

    DEFF Research Database (Denmark)

    Sørensen, Lars Korsbæk Connor; Poulsen, Anne Havemose; Bendtzen, Klaus;

    2009-01-01

    BACKGROUND: Cytokines and cytokine inhibitors have been associated with many immunoinflammatory diseases. In the present study, we examined whether peripheral blood mononuclear cell (PBMC) gene expression mirrors the corresponding plasma levels of clinically important pro- and anti-inflammatory c...

  15. Obstetrical disseminated intravascular coagulation score.

    Science.gov (United States)

    Kobayashi, Takao

    2014-06-01

    Obstetrical disseminated intravascular coagulation (DIC) is usually a very acute, serious complication of pregnancy. The obstetrical DIC score helps with making a prompt diagnosis and starting treatment early. This DIC score, in which higher scores are given for clinical parameters rather than for laboratory parameters, has three components: (i) the underlying diseases; (ii) the clinical symptoms; and (iii) the laboratory findings (coagulation tests). It is justifiably appropriate to initiate therapy for DIC when the obstetrical DIC score reaches 8 points or more before obtaining the results of coagulation tests. Improvement of blood coagulation tests and clinical symptoms are essential to the efficacy evaluation for treatment after a diagnosis of obstetrical DIC. Therefore, the efficacy evaluation criteria for obstetrical DIC are also defined to enable follow-up of the clinical efficacy of DIC therapy.

  16. C4b-binding protein protects coagulation factor Va from inactivation by activated protein C

    NARCIS (Netherlands)

    van de Poel, RHL; Meijers, JCM; Rosing, J; Tans, G; Bouma, Bonno N.

    2000-01-01

    We investigated the effect of C4BP on APC-mediated inactivation of factor Va (FVa) in the absence and presence of protein S. FVa inactivation was biphasic (k(506) = 4.4 x 10(8) M-1 s(-1), k(306) = 2.7 x 10(7) M-1 s(-1)), and protein S accelerated Arg(306) cleavage approximately 10-fold. Preincubatio

  17. [Traumatic abruption of the placenta with disseminated intravascular coagulation].

    Science.gov (United States)

    Benz, R; Malär, A-U; Benz-Wörner, J; Scherer, M; Hodel, M; Gähler, A; Haberthür, C; Konrad, C

    2012-10-01

    Trauma in pregnancy is infrequent and a systematic primary strategy constitutes a real challenge for the interdisciplinary team. With a high fetal mortality rate and a substantial maternal mortality rate traumatic placental abruption is a severe emergency which every anesthetist should be aware of. After hemodynamic stabilization of the mother and control of the viability of the fetus the therapy of traumatic placental abruption consists mostly of an immediate caesarean section. Coagulopathy by depletion of coagulation factors as well as disseminated intravascular coagulation (DIC) have to be expected and consequently a massive blood loss must be anticipated. Thrombelastography provides assistance for fast differential diagnosis and goal-directed treatment of the disturbed sections of the coagulation cascade.

  18. Acquired Factor XIII Inhibitor in Hospitalized and Perioperative Patients: A Systematic Review of Case Reports and Case Series.

    Science.gov (United States)

    Tone, Kira J; James, Tyler E; Fergusson, Dean A; Tinmouth, Alan; Tay, Jason; Avey, Marc T; Kilty, Shaun; Lalu, Manoj M

    2016-07-01

    Factor XIII (FXIII) cross-links fibrin monomers to support clot stabilization and wound healing. Acquired FXIII deficiency is caused by autoantibodies that inhibit FXIII and can result in bleeding despite normal routine coagulation test results. Given the rarity of this disease, large clinical studies are not feasible. We therefore conducted a systematic review of case reports and case series of acquired FXIII inhibitor to evaluate potential management and treatment strategies for acquired FXIII inhibitor in hospitalized and/or perioperative patients. A systematic search of MEDLINE, Embase, and Web of Science identified reports of hospitalized and perioperative patients with acquired FXIII deficiency. No restrictions were placed on language or publication type. Article screening and data extraction were performed independently by 2 abstractors. Completeness of reporting was evaluated according to modified elements from the CAse REport (CARE) guidelines. A total of 1028 citations were reviewed, with 36 case reports and 3 case series meeting eligibility criteria (63 patients total). The mean age was 60 (range, 9-87) years with balanced sex representation. At presentation, 48 patients (76%) had intramuscular or subcutaneous bleeding, and 34 patients (54%) had external or surgical bleeding. All cases were diagnosed by initially detecting a FXIII deficiency and then identifying the inhibitor. Clinical improvement in bleeding was seen in patients receiving FXIII concentrate (13/17 patients), cryoprecipitate (5/8), and plasma (10/18). Inhibitor reduction was seen in patients who received rituximab (6/6 patients), plasma exchange (2/2), intravenous immunoglobulin (4/5), steroid (15/20), and cyclophosphamide (10/15). Concurrent initiation of multiple therapies and obvious lack of control comparisons made direct association to outcomes difficult to establish. Outcomes were reported for 55 patients, with 25 patients (45%) having complete inhibitor eradication and 15 patients

  19. Do maternal and intrauterine factors influence blood pressure in childhood?

    OpenAIRE

    Whincup, P H; Cook, D G; Papacosta, O

    1992-01-01

    It has been proposed that maternal health and nutrition may be important in the development of adult cardiovascular risk, and that blood pressure may be an important intermediate step in this process. To examine the relevance of this hypothesis in contemporary British children, the relationships of several maternal factors to blood pressure were studied in 3360 children of European origin aged 5-7 years. Maternal age, height, and body mass index were all positively related to blood pressure i...

  20. Advances in Inhibitors of FXa.

    Science.gov (United States)

    Guo, Liwei; Ma, Shutao

    2015-01-01

    Thromboembolic diseases such as deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) and ischemic strokes are mainly responsible for people's morbidity and mortality and have severely affected the people's quality of life all over the world. According to WHO statistics, an average of 17 million people are killed by the thromboembolic diseases each year globally. Therefore, the prevention and treatment of thromboembolic diseases have received widespread attention in recent years. Based on thrombotic mechanism, anti-thrombotic drugs are mainly divided into anticoagulants, antiplatelet agents and direct thrombolytic drugs. In particular, anticoagulants such as vitamin K antagonists (VKAs), unfractionated heparin (UFH), and low-molecular-weight heparins (LMWHs) have become the main therapies for pre-treatment of thromboembolic disorders. However, the limitations of traditional anticoagulants such as slow onset of action, dose-adjusted requirement, drug-drug and drug-food interactions have restricted their improvement in the clinical treatment. The mechanism of the thromboembolic disorders has indicated that coagulation factor Xa (fXa) plays a pivotal role in the blood coagulation cascade. Thus, selective inhibition of fXa by diminishing the amplified generation of thrombin without affecting the pre-existing thrombin levels can provide better antithrombotic effect, thereby causing less impairment of primary hemostasis. In this paper, we mainly introduce the recent advances of fXa inhibitors, with focus on their biological activity and structure-activity relationship (SAR) information. In particular, the inspirations from the structures of the fXa inhibitors and their future direction are highlighted. PMID:25981610

  1. Drug: D08793 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08793 Drug Human blood-coagulation factor eight inhibitor bypassing activity compl... blood preparations 6343 Plasma preparations D08793 Human blood-coagulation factor eight inhibitor bypassing activity complex, dried PubChem: 96025476 ...

  2. Motivating Factors and Potential Deterrents to Blood Donation in High School Aged Blood Donors.

    Science.gov (United States)

    Finck, Rachel; Ziman, Alyssa; Hoffman, Matthew; Phan-Tang, Michelle; Yuan, Shan

    2016-01-01

    Background. To ensure an adequate supply of blood, collection centers must design campaigns that successfully recruit and maintain an active donor pool. Understanding factors that motivate and deter individuals from donating may help centers develop targeted recruitment campaigns. These factors among high school aged blood donors have not yet been fully investigated. Study Design and Methods. A voluntary, anonymous survey was administered to student donors at high school mobile blood drives. The survey instrument asked the students to rate several potential motivating factors in their importance in the decision to donate blood and several potential deterring factors in their future decision whether or not to donate blood again. The survey also asked the students to rate the desirability of several potential incentives. Results. Motivating factors that reflected prosocial, empathetic, and altruistic thoughts and beliefs were rated highly by students. Pain from phlebotomy was most commonly chosen as potential deterrent. Movie tickets and cookies/snacks at the drive were rated as the most attractive incentives. Conclusion. High school aged blood donors are similar to other donor groups in their expressed motives for donating blood. This group may be unique in the factors that deter them from donating and in their preferences for different incentives. PMID:27293985

  3. Motivating Factors and Potential Deterrents to Blood Donation in High School Aged Blood Donors

    Directory of Open Access Journals (Sweden)

    Rachel Finck

    2016-01-01

    Full Text Available Background. To ensure an adequate supply of blood, collection centers must design campaigns that successfully recruit and maintain an active donor pool. Understanding factors that motivate and deter individuals from donating may help centers develop targeted recruitment campaigns. These factors among high school aged blood donors have not yet been fully investigated. Study Design and Methods. A voluntary, anonymous survey was administered to student donors at high school mobile blood drives. The survey instrument asked the students to rate several potential motivating factors in their importance in the decision to donate blood and several potential deterring factors in their future decision whether or not to donate blood again. The survey also asked the students to rate the desirability of several potential incentives. Results. Motivating factors that reflected prosocial, empathetic, and altruistic thoughts and beliefs were rated highly by students. Pain from phlebotomy was most commonly chosen as potential deterrent. Movie tickets and cookies/snacks at the drive were rated as the most attractive incentives. Conclusion. High school aged blood donors are similar to other donor groups in their expressed motives for donating blood. This group may be unique in the factors that deter them from donating and in their preferences for different incentives.

  4. RIVAROXABAN: AN ORAL DIRECT INHIBITOR OF FACTOR X-A

    Directory of Open Access Journals (Sweden)

    Mehta Hiren R

    2011-08-01

    Full Text Available Venous thrombo embolism (VTE, which includes deep vein thrombosis and pulmonary embolism, is a major cause of morbidity and mortality in patients undergoing major orthopaedic surgery, and routine thrombo prophylaxis has been the standard of care over the last 20 years. Currently available options for the prevention of venous thrombo embolism in major orthopedic surgery include low-molecular-weight heparins, vitamin K antagonists and, more recently, the synthetic pentasaccharide fondaparinux. Although effective, these drugs have several limitations, and new oral antithrombotics offering predictable, effective and safe anticoagulation are strongly needed. This overview focuses on the most advanced oral direct inhibitors of factor Xa, rivaroxaban.Rivaroxaban, an oral oxazolidinone-based anticoagulant, is a potent, selective direct inhibitor of factor Xa that is used in the prevention of venous thrombo embolism in adult patients after total hip replacement (THR or total knee replacement (TKR surgery. In four large, clinical trials, oral rivaroxaban was more effective than subcutaneous enoxaparin in preventing postoperative VTE in patients undergoing total hip replacement or total knee replacement surgery. Notably, the superior efficacy of rivaroxaban was achieved with a low but not significant increase in the incidence of major bleeding episodes. In addition, preliminary pharma co-economic analyses in several countries indicate that rivaroxaban is a cost-effective treatment strategy versus enoxaparin. Although the position of rivaroxaban relative to other therapies remains to be fully determined, it is an effective emerging option for the prevention of venous thrombo embolism following total hip replacement and total knee replacement.

  5. Recombinant activated factor Ⅶ in hemophagocytic lymphohistiocytosis with disseminated intravascular coagulation

    Institute of Scientific and Technical Information of China (English)

    ZHUANG Jun-ling; JIANG Qing-wei; XU Ying; WANG Shu-jie

    2011-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a lifethreatening disorder due to hyperinflammation resulting in infiltration of different organs with extensive hemophagocytosis. Severe coagulopathy was one of the main reasons for death in HLH. Over secretion of plasminogen activator by activated macrophages leads to hyperfibrinolysis. We reported a 36-year-old woman who was diagnosed as HLH probably secondary to lymphoma. Massive bleeding from gut and retroperitoneal area were not able to be controlled by conventional hemostatic treatments. This patient received one dose recombinant activated factor Ⅶ (rFVlla) 3.6 mg (70 μg/kg). Hemostatic effect was achieved in 0.5 hour and lasted 24 hours. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were quickly corrected to normal ranges.Fibrinogen level elevated from 0.5 g/L before using rFVIla to 1.8 g/L 20 hours after. Although dexamethasone and etopside were administrated to treat HLH, this patient died from septic shock after persistent neutropenia. This suggests that rFVlla may be effective in the management of intractable hemorrhage in patients with HLH.

  6. Risk Factors Of Thrombogenic Complications in Patients with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ivanenko I.L.

    2010-12-01

    Full Text Available The results of analysis of blood coagulative system in patients of mammary gland cancer are obtained. Risk factors of thrombogenic complications development were revealed with the use of methods of evaluation of platelet-vascular and plasma links of hemostasis. The necessity of blood coagulative and anticoagulative systems breakage revealing before operation for preventive measures performances is shown

  7. New Infestin-4 Mutants with Increased Selectivity against Factor XIIa.

    Science.gov (United States)

    Kolyadko, Vladimir N; Lushchekina, Sofya V; Vuimo, Tatiana A; Surov, Stepan S; Ovsepyan, Ruzanna A; Korneeva, Vera A; Vorobiev, Ivan I; Orlova, Nadezhda A; Minakhin, Leonid; Kuznedelov, Konstantin; Severinov, Konstantin V; Ataullakhanov, Fazoil I; Panteleev, Mikhail A

    2015-01-01

    Factor XIIa (fXIIa) is a serine protease that triggers the coagulation contact pathway and plays a role in thrombosis. Because it interferes with coagulation testing, the need to inhibit fXIIa exists in many cases. Infestin-4 (Inf4) is a Kazal-type inhibitor of fXIIa. Its specificity for fXIIa can be enhanced by point mutations in the protease-binding loop. We attempted to adapt Inf4 for the selective repression of the contact pathway under various in vitro conditions, e.g., during blood collection and in 'global' assays of tissue factor (TF)-dependent coagulation. First, we designed a set of new Inf4 mutants that, in contrast to wt-Inf4, had stabilized canonical conformations during molecular dynamics simulation. Off-target activities against factor Xa (fXa), plasmin, and other coagulation proteases were either reduced or eliminated in these recombinant mutants, as demonstrated by chromogenic assays. Interactions with fXIIa and fXa were also analyzed using protein-protein docking. Next, Mutant B, one of the most potent mutants (its Ki for fXIIa is 0.7 nM) was tested in plasma. At concentrations 5-20 μM, this mutant delayed the contact-activated generation of thrombin, as well as clotting in thromboelastography and thrombodynamics assays. In these assays, Mutant B did not affect coagulation initiated by TF, thus demonstrating sufficient selectivity and its potential practical significance as a reagent for coagulation diagnostics. PMID:26670620

  8. New Infestin-4 Mutants with Increased Selectivity against Factor XIIa.

    Directory of Open Access Journals (Sweden)

    Vladimir N Kolyadko

    Full Text Available Factor XIIa (fXIIa is a serine protease that triggers the coagulation contact pathway and plays a role in thrombosis. Because it interferes with coagulation testing, the need to inhibit fXIIa exists in many cases. Infestin-4 (Inf4 is a Kazal-type inhibitor of fXIIa. Its specificity for fXIIa can be enhanced by point mutations in the protease-binding loop. We attempted to adapt Inf4 for the selective repression of the contact pathway under various in vitro conditions, e.g., during blood collection and in 'global' assays of tissue factor (TF-dependent coagulation. First, we designed a set of new Inf4 mutants that, in contrast to wt-Inf4, had stabilized canonical conformations during molecular dynamics simulation. Off-target activities against factor Xa (fXa, plasmin, and other coagulation proteases were either reduced or eliminated in these recombinant mutants, as demonstrated by chromogenic assays. Interactions with fXIIa and fXa were also analyzed using protein-protein docking. Next, Mutant B, one of the most potent mutants (its Ki for fXIIa is 0.7 nM was tested in plasma. At concentrations 5-20 μM, this mutant delayed the contact-activated generation of thrombin, as well as clotting in thromboelastography and thrombodynamics assays. In these assays, Mutant B did not affect coagulation initiated by TF, thus demonstrating sufficient selectivity and its potential practical significance as a reagent for coagulation diagnostics.

  9. 牛乳的凝固特性及其影响因素研究进展%Research advances on milk coagulation properties and influencing factors

    Institute of Scientific and Technical Information of China (English)

    孙雨辰; 王辑; 郑喆; 杨贞耐

    2014-01-01

    本文综述了近年来有关牛乳凝固特性的研究进展,重点针对影响牛乳凝固能力的遗传和非遗传因素的研究进展进行了分析论述,包括不同来源牛乳的凝固特性、乳蛋白组分和工艺条件等对牛乳凝固能力的影响。旨在厘清影响牛乳凝固能力的主要因素。%This paper mainly reviewed the research progress on the milk coagulation properties and the influencing factors, including the milk coagulation ability of different sources of milk, and the effects of milk protein components and processing technology on the milk coagulation ability, aiming to clarify the main factors affecting the milk clotting ability.

  10. The effects of infrasound on the blood coagulation function of guinea pigs%次声对豚鼠凝血功能的影响

    Institute of Scientific and Technical Information of China (English)

    马文敏; 亓鹏; 张建中; 易勇; 陈兴明; 张军; 韩瑞刚

    2011-01-01

    Objective To study the change of the blood coagulation function of guinea pigs exposed to 16 Hz/120 dB, 16 Hz/125 dB infrasound and to explore the mechanism of circulation system damage.Methods Seventy-two guinea pigs were divided into 3 groups: the control group, the group exposed to 16 Hz/120 dB infrasound for 1.5 h a day and the group exposed to 16 Hz/125 dB infrasound for 1.5 h a day. Each exposure group was divided into 4 sub-groups (8 guinea pigs a sub-group) which were exposed to infrasound for 1, 7, 14 and 21 d, respectively. The coagulation function and serum nitric oxide (NO) were measured for control group and all sub-groups after exposure to infrasound. Results The prothrombin time (PT),international normalized ratio (INR) and serum NO of group exposed to 16 Hz/125 dB infrasound were (31.16±3.05) s, 2.53±1.21 and (88.304±52.601)μmol/L, respectively, which were significantly higher than those [(21.36±0.10) s, 1.65±0.07 and (30.943±26.864) μ mol[L] of control group (P<0.05). PT and INR of sub-groups exposed to 16 Hz/125 dB infrasound for 14 and 21 d were significantly higher than those of control group. NO of sub-groups exposed to 16 Hz/125 dB infrasound for 1 week and 2 weeks were significantly higher than that of control group (P<0.05), but NO of sub-group exposed to 16 Hz/125 dB infrasound for 3 weeks decreased slightly. Conclusion The blood coagulation function of guinea pigs exposed to 16 Hz/125 dB infrasound decreased, PT and INR may be used as the indexes to assess of blood coagulation function change induced by the infrasound exposure.%目的 研究16 Hz、120 dB,16 Hz、125 dB次声暴露后豚鼠凝血功能的变化规律,探讨次声造成生物体循环系统损害的机制.方法 将豚鼠分为对照组及16 Hz、120 dB,16 Hz、125 dB 2个暴露组,每个暴露组均按暴露时间再分成1、7、14、21 d 4个时间亚组,每个亚组8只豚鼠.各个暴露亚组每日暴露1.5 h,分别连续暴露相应的天数后抽取血

  11. Factors influencing intraoperative blood loss in orthognathic surgery.

    Science.gov (United States)

    Thastum, M; Andersen, K; Rude, K; Nørholt, S E; Blomlöf, J

    2016-09-01

    This retrospective study aimed to identify factors of importance for intraoperative blood loss relative to total blood volume in patients undergoing orthognathic surgery. The study included 356 patients treated consecutively at a Danish university hospital between 1 January 2010 and 31 December 2012. Inclusion criteria were (1) patient age ≥18 years and (2) patient undergoing a three-piece Le Fort I osteotomy, a bilateral sagittal split osteotomy, or a combination of the two. The patient-specific relative blood loss was calculated as a percentage by dividing the intraoperative blood loss by the estimated preoperative total blood volume, and then correlated with body mass index (BMI), age, sex, operating time, and treatment modality in a multivariate stepwise regression analysis. Operating time (Psurgery, a prolonged operating time, and reduced BMI significantly increase the intraoperative relative blood loss in patients undergoing orthognathic surgery.

  12. Exactin: A specific inhibitor of Factor X activation by extrinsic tenase complex from the venom of Hemachatus haemachatus.

    Science.gov (United States)

    Girish, Vallerinteavide Mavelli; Kini, R Manjunatha

    2016-01-01

    Unwanted clots lead to heart attack and stroke that result in a large number of deaths. Currently available anticoagulants have some drawbacks including their non-specific actions. Therefore novel anticoagulants that target specific steps in the coagulation pathway are being sought. Here we describe the identification and characterization of a novel anticoagulant protein from the venom of Hemachatus haemachatus (African Ringhals cobra) that specifically inhibits factor X (FX) activation by the extrinsic tenase complex (ETC) and thus named as exactin. Exactin belongs to the three-finger toxin (3FTx) family, with high sequence identity to neurotoxins and low identity to the well-characterized 3FTx anticoagulants-hemextin and naniproin. It is a mixed-type inhibitor of ETC with the kinetic constants, Ki' and Ki determined as 30.62 ± 7.73 nM and 153.75 ± 17.96 nM, respectively. Exactin does not bind to the active site of factor VIIa and factor Xa based on its weak inhibition (IC50 ≫ 300 μM) to the amidolytic activities of these proteases. Exactin shows exquisite macromolecular specificity to FX activation as compared to factor IX activation by ETC. Exactin thus displays a distinct mechanism when compared to other anticoagulants targeting ETC, with its selective preference to ETC-FX [ES] complex. PMID:27558950

  13. Exactin: A specific inhibitor of Factor X activation by extrinsic tenase complex from the venom of Hemachatus haemachatus

    Science.gov (United States)

    Girish, Vallerinteavide Mavelli; Kini, R. Manjunatha

    2016-01-01

    Unwanted clots lead to heart attack and stroke that result in a large number of deaths. Currently available anticoagulants have some drawbacks including their non-specific actions. Therefore novel anticoagulants that target specific steps in the coagulation pathway are being sought. Here we describe the identification and characterization of a novel anticoagulant protein from the venom of Hemachatus haemachatus (African Ringhals cobra) that specifically inhibits factor X (FX) activation by the extrinsic tenase complex (ETC) and thus named as exactin. Exactin belongs to the three-finger toxin (3FTx) family, with high sequence identity to neurotoxins and low identity to the well-characterized 3FTx anticoagulants-hemextin and naniproin. It is a mixed-type inhibitor of ETC with the kinetic constants, Ki’ and Ki determined as 30.62 ± 7.73 nM and 153.75 ± 17.96 nM, respectively. Exactin does not bind to the active site of factor VIIa and factor Xa based on its weak inhibition (IC50 ≫ 300 μM) to the amidolytic activities of these proteases. Exactin shows exquisite macromolecular specificity to FX activation as compared to factor IX activation by ETC. Exactin thus displays a distinct mechanism when compared to other anticoagulants targeting ETC, with its selective preference to ETC-FX [ES] complex. PMID:27558950

  14. The effects of selective serotonin reuptake inhibitors on platelet function in whole blood and platelet concentrates.

    Science.gov (United States)

    Reikvam, Anne-Grete; Hustad, Steinar; Reikvam, Håkon; Apelseth, Torunn Oveland; Nepstad, Ina; Hervig, Tor Audun

    2012-01-01

    Several studies report that patients who are treated with selective serotonin reuptake inhibitors (SSRIs) for depression may have increased risk of bleeding, particularly from the gastrointestinal tract. This may be related to low intraplatelet serotonin concentrations. Several blood banks do not store platelets from donors using SSRIs for transfusion, although the possible effects of SSRIs on platelet storage are not documented. We conducted a case-control pilot study of apheresis platelet concentrates prepared from donors using SSRIs (n=8) and from donors without medication (n=10). The platelet concentrates were stored for 5 days. Light transmission aggregometry (LTA), thrombelastography (TEG), and flow cytometric analyses were preformed for in vitro measurements of platelet function. Platelet function and platelet serotonin content were investigated in whole blood and in platelet concentrates stored for up to 5 days. LTA, TEG, and flow cytometric analysis of glycoprotein expression did not reveal any significant differences between the two groups. All 18 platelet concentrates performed well according to the standards set for platelet quality in relation to transfusion. Blood donors using SSRIs had significantly lower platelet serotonin compared to blood donors without medication. The results from our pilot study indicate that platelets from donors using SSRIs may be suitable for transfusion after storage for 5 days, but further laboratory and clinical studies are necessary to confirm this.

  15. Role of the reprogramming factor KLF4 in blood formation.

    Science.gov (United States)

    Park, Chun Shik; Shen, Ye; Lewis, Andrew; Lacorazza, H Daniel

    2016-05-01

    Krüppel-like factor 4 is a zinc finger protein with dual functions that can act as a transcriptional activator and repressor of genes involved in cell proliferation, differentiation, and apoptosis. Although most studies have focused on terminally differentiated epithelial cells, evidence suggests that Krüppel-like factor 4 regulates the development and function of the myeloid and lymphoid blood lineages. The ability of Krüppel-like factor 4 to dedifferentiate from somatic cells into pluripotent stem cells in cooperation with other reprogramming factors suggests its potential function in the preservation of tissue-specific stem cells. Additionally, emerging interest in the redifferentiation of induced pluripotent stem cells into blood cells to correct hematologic deficiencies and malignancies warrants further studies on the role of Krüppel-like factor 4 in steady-state blood formation. PMID:26908828

  16. Procoagulants and anticoagulants in fetal blood. A literature survey.

    Directory of Open Access Journals (Sweden)

    Waldemar Uszyński

    2010-05-01

    Full Text Available In intrauterine life, hemostasis is maintained by the same components as in extrauterine life (blood platelets, coagulation and fibrinolysis systems, involvement of the vascular wall; in the fetus, however, these components show significant differences of a quantitative/qualitative nature. In the present study, we surveyed the literature on the coagulation system in the fetus. We focused on the velocity of development of the coagulation system, being reflected in the increased concentration of all procoagulants and anticoagulants (a rise from approximately 20% in the middle of pregnancy to about 60% or more in the period of labor; exceptions: factors V, VIII and XIII which in the labor period reach the adult level and screening test results (prothrombin time, aPTT - activated prothrombin time, and thrombin time. Reference values were given for the 19-38 weeks of pregnancy and the labor term. Biochemical features of fetal fibrinogen and PIVKA factors were also discussed. The role of activated protein C (APC in the maintenance of balance between procoagulants and anticoagulants was postulated as well as the role of APC in the formation of thrombin activatable fibrinolysis inhibitor (TAFI.

  17. Factor VIII gene variants and inhibitor risk in African American hemophilia A patients.

    Science.gov (United States)

    Gunasekera, Devi; Ettinger, Ruth A; Nakaya Fletcher, Shelley; James, Eddie A; Liu, Maochang; Barrett, John C; Withycombe, Janice; Matthews, Dana C; Epstein, Melinda S; Hughes, Richard J; Pratt, Kathleen P

    2015-08-13

    African American hemophilia A (HA) patients experience a higher incidence of neutralizing anti-factor VIII (FVIII) antibodies ("inhibitors") vis-à-vis white patients. Nonsynonymous single-nucleotide polymorphisms (ns-SNPs) in the F8 gene encoding FVIII-H484, FVIII-E1241, and FVIII-V2238 are more prevalent in African Americans. This study tested the hypothesis that immune responses to these sites provoke inhibitors. Blood samples were obtained from 174 African American and 198 white HA subjects and their F8 gene sequences determined. Major histocompatibility complex class II binding and T-cell recognition of polymorphic sequences were evaluated using quantitative binding assays and HLA-DRB1 tetramers. Peptides corresponding to 4 common ns-SNPs showed limited binding to 11 HLA-DRB1 proteins. CD4 T cells from 22 subjects treated with FVIII products having sequences at residues FVIII-484, 1241, and 2238 differing from those of putative proteins encoded by their F8 genes did not show high-avidity tetramer binding, whereas positive-control staining of tetanus-specific CD4 T cells was routinely successful. African Americans with an intron-22 inversion mutation showed a 2-3 times-higher inhibitor incidence than whites with the same mutation (odds ratio = 2.3 [1.1-5.0, P = .04]), but this did not correlate with any of the ns-SNPs. We conclude that immune responses to "sequence-mismatched" FVIII products are unlikely to contribute appreciably to the inhibitor incidence in African Americans.

  18. Effect of different time on coagulation factors in fresh frozen plasma after thawing%不同放置时间对融化后新鲜冰冻血浆中凝血因子的影响

    Institute of Scientific and Technical Information of China (English)

    徐会芹

    2015-01-01

    Objective To investigate the effect of different time on coagulation factors in fresh frozen plasma after thawing.Methods The medicine blood by ACD B anticoagulated whole blood separation, preparation and fresh frozen plasma30,37℃ water bath melting and melt after 0,6,12,24h determination of prothrombin time (PT),activated partial thromboplastin time(APTT),fibrinogen(FIB),thrombin time (TT),coagulation factor FⅦ、FⅧ、FⅨ activity level.ResultsAfter the fresh frozen plasma,the PT,APTT,FIB,TT at different time points of the test results were not statistically different in 24 hours(P>0.05).Coagulation factor FⅦ and FⅧ changed with time and significantly decreased with the passage of time attenuation and blood immediate difference was statistically significant(P<0.05). FIX only when 12 hours had decreased,again after 24 hours.ConclusionFresh frozen plasma should be infused immediately after thawing,so as to guarantee the biological activity of coagulation factor and guarantee the effect of treatment.%目的:探讨不同放置时间对融化后新鲜冰冻血浆中凝血因子的影响。方法选择本院血站经ACD-B抗凝全血分离制备而成的新鲜冰冻血浆30份,37℃水浴融化,于融化后0、6、12、24h测定凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白(FIB)、凝血酶时间(TT)、凝血因子FⅦ、FⅧ、FⅨ活性水平。结果新鲜冷冻血浆融化后,PT、APTT、FIB、TT在24h内不同时间点测定结果,差异无统计学意义( P>0.05)。凝血因子FⅦ及FⅧ随时间的改变而有明显的降低,随着时间的推移衰减,与抽血即刻比较差异有统计学意义(P<0.05)。而FⅨ仅在12h的时候有一过性的下降,24h后又恢复。结论新鲜冰冻血浆在融化后应该立即输注,以保证凝血因子生物学活性,进一步保证治疗的效果。

  19. 58例妊娠高血压疾病凝血四项结果分析%The Study on Four Blood Coagulation Indexes of 58 Cases of Gestational Hypertension

    Institute of Scientific and Technical Information of China (English)

    刘淑玲; 武雪征; 任淑媛

    2011-01-01

    Objective To detect the function of blood coagulation for pregnant women with gestational hypertension, and to elucidate its clinical significance and application. Methods The results of prothrombin time,activated partial thromboplastin time, fibrinogen( FIB ), D-Dimer ( D-D )for pregnant women with or without hypertension( each group 58 cases ), and randomly selected normal unpregnant women( 88 cases ) were compared using BECKMAN( ACL9000 )to test the four parameters of blood coagulation. Results Blood coagulation tests showed that FIB and D-D of pregnant women were slightly or notably increased compared with unpregnant women( P < 0.01 ). FIB and D-D of pregnant women with hypertension were higher than those of normal pregnancy( P < 0.01 ). Conclusion Regular inspection of the blood coagulation for pregnant women is significant to early diagnosis and treatment for the gestational hypertension, which is also a guidance to monitor the pregnant women' s blood coagulation, providing scientfic laboratory basis for the pregnant woman health and normal fetus development.%目的通过对妊娠高血压疾病的妇女凝血四项结果的分析,总结其变化规律并应用于临床.方法用美国贝克曼ACL9000血凝仪对正常妊娠和患有妊娠期高血压疾病患者(各58例)及随机抽取的正常非妊娠妇女(88例为对照组)进行血凝四项的测定:凝血酶原时间、活化部分凝血酶时间、纤维蛋白原(FIB)、D-二聚体(D-D),并进行分析.结果妊娠高血压组血浆FIB、D-D的含量均高于非妊娠组(P<0.01).妊娠高血压疾病组的FIB及D-D高于正常妊娠组(P<0.01).结论定期检测孕妇血浆中凝血四项,对妊娠高血压疾病的早期诊断和治疗具有重要意义,対妊娠孕妇凝血机制的监测具有指导意义,为孕妇健康和胎儿的正常发育提供科学的实验依据.

  20. Spatial coagulation with bounded coagulation rate

    CERN Document Server

    Bailleul, Ismael

    2010-01-01

    We prove that the spatial coagulation equation with bounded coagulation rate is well-posed for all times in a given class of kernels if the convection term of the underlying particle dynamics has divergence bounded above by a negative constant. Multiple coagulations, fragmentation and scattering are also considered.

  1. Manipulating adenovirus hexon hypervariable loops dictates immune neutralisation and coagulation factor X-dependent cell interaction in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Jiangtao Ma

    2015-02-01

    Full Text Available Adenoviruses are common pathogens, mostly targeting ocular, gastrointestinal and respiratory cells, but in some cases infection disseminates, presenting in severe clinical outcomes. Upon dissemination and contact with blood, coagulation factor X (FX interacts directly with the adenovirus type 5 (Ad5 hexon. FX can act as a bridge to bind heparan sulphate proteoglycans, leading to substantial Ad5 hepatocyte uptake. FX "coating" also protects the virus from host IgM and complement-mediated neutralisation. However, the contribution of FX in determining Ad liver transduction whilst simultaneously shielding the virus from immune attack remains unclear. In this study, we demonstrate that the FX protection mechanism is not conserved amongst Ad types, and identify the hexon hypervariable regions (HVR of Ad5 as the capsid proteins targeted by this host defense pathway. Using genetic and pharmacological approaches, we manipulate Ad5 HVR interactions to interrogate the interplay between viral cell transduction and immune neutralisation. We show that FX and inhibitory serum components can co-compete and virus neutralisation is influenced by both the location and extent of modifications to the Ad5 HVRs. We engineered Ad5-derived HVRs into the rare, native non FX-binding Ad26 to create Ad26.HVR5C. This enabled the virus to interact with FX at high affinity, as quantified by surface plasmon resonance, FX-mediated cell binding and transduction assays. Concomitantly, Ad26.HVR5C was also sensitised to immune attack in the absence of FX, a direct consequence of the engineered HVRs from Ad5. In both immune competent and deficient animals, Ad26.HVR5C hepatic gene transfer was mediated by FX following intravenous delivery. This study gives mechanistic insight into the pivotal role of the Ad5 HVRs in conferring sensitivity to virus neutralisation by IgM and classical complement-mediated attack. Furthermore, through this gain-of-function approach we demonstrate the dual

  2. 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.

  3. Soluble vascular endothelial growth factor in various blood transfusion components

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Werther, K; Mynster, T;

    1999-01-01

    BACKGROUND: Blood transfusion may reduce survival after curative surgery for solid tumors. This may be related to extracellular content of cancer growth factors present in transfusion components. Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis in solid tumors...

  4. Changes in platelet function, blood coagulation and fibrinolysis during insulin-induced hypoglycaemia in juvenile diabetics and normal subjects

    DEFF Research Database (Denmark)

    Dalsgaard-Nielsen, J; Madsbad, S; Hilsted, J

    1982-01-01

    in the diabetics after hypoglycaemia, whereas no changes were seen in the control group. The activated partial thromboplastin time (APTT) was reduced in both groups and significantly lower in the diabetics than in the controls 120 min after insulin infusion. Fibrinogen and factor VIII R:Ag increased after insulin...... infusion; highest values were seen in the diabetics. The euglobulin clot lysis time (ELT) was reduced in both groups during insulin infusion; 120 min after end of insulin infusion ELT was significantly longer in the diabetics than in the control group.......Haemostatic parameters were assessed before insulin induced hypoglycaemia and 0, 1 and 2 hr after discontinuation of insulin infusion in 7 non-diabetics, aged 28 (22-31) years (mean and range), and 8 juvenile diabetics, aged 31 (27-35) years, with a mean duration of diabetes of 4 years...

  5. The action of Lonomia achelous caterpillar venom on some blood coagulation and fibrinolysis parameters of the rabbit.

    Science.gov (United States)

    Marval, E; Guerrero, B; Arocha-Piñango, C L

    1999-11-01

    The bodily secretions of the Lonomia achelous caterpillar cause a severe and often fatal acquired bleeding diathesis in humans. The rabbit was selected as model animal in an attempt to understand the mode of action of the venom. The animals were injected subcutaneously with either hemolymph or chromatographically purified fractions. Injections of hemolymph produced a drop in fibrinogen and factor XIII levels and an increase in fibrinogen degradation products (FDP). In addition one batch of hemolymph decreased plasminogen levels. The chromatographically semipurified fraction II decreased both fibrinogen and plasminogen. The effect was dose dependent but, unlike in humans, there was a fairly rapid return to baseline values. In conclusion, the response to Lonomia achelous venom in the rabbit is similar to the response seen in humans, but with a more rapid recovery. PMID:10482385

  6. Soluble vascular endothelial growth factor in various blood transfusion components

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Werther, K; Mynster, T;

    1999-01-01

    BACKGROUND: Blood transfusion may reduce survival after curative surgery for solid tumors. This may be related to extracellular content of cancer growth factors present in transfusion components. Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis in solid tumors....... The potential content of VEGF in various blood components for transfusion was evaluated. STUDY DESIGN AND METHODS: Soluble VEGF (sVEGF, isotype 165) was determined by an enzyme-linked immunosorbent assay (EIA) in serum and plasma samples and in lysed cells from healthy volunteers. Subsequently, total content......-reduced PRP. The sVEGF accumulated significantly in WB, SAGM blood, and BCP pools, depending on the storage time. CONCLUSION: The sVEGF (isotype 165) appears to be present in various blood transfusion components, depending on storage time....

  7. Pro- and anticoagulant properties of factor V in pathogenesis of thrombosis and bleeding disorders.

    Science.gov (United States)

    Dahlbäck, Björn

    2016-05-01

    Factor V (FV) serves an important role in the regulation of blood coagulation, having both pro- and anticoagulant properties. The circulating high molecular weight single-chain FV molecule undergoes a series of proteolytic cleavages during both activation of coagulation and during anticoagulant regulation of coagulation by activated protein C (APC). It is noteworthy that mutations in the factor V gene (F5) either cause thrombosis or bleeding. New insights into the importance and complexity of FV functions have been generated from elucidation of the pathogenic mechanisms of two familial mutations in the F5 gene. The first mutation was identified as a result of the discovery of APC resistance as the most common risk factor for venous thrombosis. The mutation (FV Leiden) predicts the Arg(506) Gln replacement, which impairs the normal regulation of FVa by APC, as the Arg506 site is an important APC cleavage site. In addition, elucidation of APC resistance resulted in the discovery of the anticoagulant APC cofactor activity of FV. The second FV mutation (FV(A2440G) ), identified in a family with an autosomal dominant bleeding disorder, has led to the discovery of an alternative splicing generating a previously unidentified FV isoform (FV-Short), which inhibits coagulation via an unexpected and intriguing mechanism involving the coagulation inhibitor TFPI-α. These are naturally occurring mutations in the F5 gene that have generated new knowledge on the role of FV in regulation of coagulation and the importance of genetic risk factors for thrombosis and bleeding. PMID:27161771

  8. Characterization of the intracellular signalling capacity of natural FXa mutants with reduced pro-coagulant activity

    NARCIS (Netherlands)

    M. Monti; K.S. Borensztajn; M. Pinotti; A. Canella; A. Branchini; G. Marchetti; P.H. Reitsma; F. Bernardi; C.A. Spek

    2009-01-01

    INTRODUCTION: Factor X (FX) is a serine-protease playing a crucial role in the blood coagulation pathway and triggering intracellular signalling in a variety of cells via protease-activated receptors (PARs). By exploiting naturally occurring variants (V342A and G381D, catalytic domain; E19A, gamma-c

  9. Genotyping analysis for the 46 C/T polymorphism of coagulation factor XII and the involvement of factor XII activity in patients with recurrent pregnancy loss.

    Directory of Open Access Journals (Sweden)

    Eriko Asano

    Full Text Available BACKGROUND: Established causes of recurrent pregnancy loss (RPL include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations and abnormal embryonic karyotype. A systematic review concluded that coagulation factor XII (FXII deficiency was associated with RPL. However, it could not be established whether the 46 C/T SNP of FXII or low activity of FXII was a risk factor for RPL, because of the small sample size. METHODS AND FINDINGS: We conducted a cross-sectional and cohort study in 279 patients with two or more unexplained consecutive pregnancy losses and 100 fertile women. The association between the lupus anticoagulant (LA activity and FXII activity was examined. The frequency of the CC, CT and TT genotypes and the FXII activity were also compared between the patients and controls. Subsequent miscarriage rates among the CC, CT, TT genotypes and according to the FXII activity was examined. LA was associated with reduced FXII activity. The CT, but not the TT, genotype was confirmed to be a risk factor for RPL in the cross-sectional study using multivariate logistic regression analysis (OR, 2.8; 95% CI, 1.37-5.85. The plasma FXII activity in the patients was similar to that in the controls. Neither low FXII activity nor the CT genotype predicted the subsequent pregnancy outcome in the cohort study. On the other hand, and intermediate FXII activity level of 85-101% was predictive of subsequent miscarriage. CONCLUSIONS: Low FXII activity was not associated with RPL. The FXII gene was found to be one of the significant susceptibility genes for RPL, similar to the FV Leiden mutation. However, the clinical influence of the CT genotype might be relatively small, because the presence/absence of this genotype did not have any predictive value for the subsequent pregnancy outcome. This was the first study indicating the influence of FXII 46C/T on further pregnancy outcomes.

  10. Factors Associated with Repeat Blood Donation at the Northern Zone Blood Transfusion Centre in Tanzania

    OpenAIRE

    Mauka, Wilhellmuss I.; Mahande, Michael J; Msuya, Sia E; Rune N. Philemon

    2015-01-01

    Background and Objective. The aim of this study was to determine factors associated with repeat blood donation. Methods. This was a cross-sectional study carried out among blood donors aged 18–65 years in northern Tanzania. The questionnaire was administered among 454 participants through the phone. Results. Of the 454 participants, the proportion of repeat donation was 63.9%. In the backward logistic regression analysis, the significant predictors were living in Arusha which had lower odds o...

  11. Anticoagulant therapy with the oral direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban and the thrombin inhibitor dabigatran etexilate in patients with hepatic impairment.

    Science.gov (United States)

    Graff, Jochen; Harder, Sebastian

    2013-04-01

    The direct factor Xa (FXa) inhibitors rivaroxaban, apixaban and edoxaban, and the thrombin inhibitor dabigatran etexilate (dabigatran) have gained approval for use in several indications, most notably for the prevention and treatment of venous thromboembolism (VTE) and for the prevention of stroke in patients with atrial fibrillation. Hepatic impairment can affect the disposition of these anticoagulants considerably not only because of the hepatic metabolism of the direct FXa inhibitors but also because moderate to severely impaired hepatic function will affect coagulation. This review describes the key pharmacological properties of novel oral anticoagulants with special attention to patients with impaired hepatic function. In subjects with moderately impaired liver function (i.e. Child-Pugh classification B), the area under the plasma concentration-time curve (AUC) of rivaroxaban (10 mg single dose) is increased by 2.27-fold, which is paralleled by an increase in FXa inhibition. The AUC of apixaban (5 mg single dose) is increased by 1.09-fold, whereas the AUC of edoxaban (15 mg single dose) is decreased by 4.8 % and the AUC of dabigatran (150 mg single dose) is decreased by 5.6 %. Specific labelling restrictions for rivaroxaban, apixaban and dabigatran regarding impaired hepatic function are based on both the Child-Pugh classification and liver-related exclusion criteria applied in pivotal clinical trials. Rivaroxaban is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including cirrhotic patients classified as Child-Pugh B and C. Apixaban can be used with caution in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment or in patients with alanine aminotransferase and aspartate aminotransferase levels >2× upper limit of normal (ULN). Apixaban is not recommended in patients with severe hepatic impairment and is contraindicated in those with hepatic disease associated with

  12. Cardiovascular effects of dipeptidyl peptidase-4 inhibitors: from risk factors to clinical outcomes.

    Science.gov (United States)

    Scheen, André J

    2013-05-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are oral incretin-based glucose-lowering agents with proven efficacy and safety in the management of type 2 diabetes mellitus (T2DM). In addition, preclinical data and mechanistic studies suggest a possible additional non-glycemic beneficial action on blood vessels and the heart, via both glucagon-like peptide-1-dependent and glucagon-like peptide-1-independent effects. As a matter of fact, DPP-4 inhibitors improve several cardiovascular risk factors: they improve glucose control (mainly by reducing the risk of postprandial hyperglycemia) and are weight neutral; may lower blood pressure somewhat; improve postprandial (and even fasting) lipemia; reduce inflammatory markers; diminish oxidative stress; improve endothelial function; and reduce platelet aggregation in patients with T2DM. In addition, positive effects on the myocardium have been described in patients with ischemic heart disease. Results of post hoc analyses of phase 2/3 controlled trials suggest a possible cardioprotective effect with a trend (sometimes significant) toward lower incidence of major cardiovascular events with sitagliptin, vildagliptin, saxagliptin, linagliptin, or alogliptin compared with placebo or other active glucose-lowering agents. However, the definite relationship between DPP-4 inhibition and better cardiovascular outcomes remains to be proven. Major prospective clinical trials involving various DPP-4 inhibitors with predefined cardiovascular outcomes are under way in patients with T2DM and a high-risk cardiovascular profile: the Sitagliptin Cardiovascular Outcome Study (TECOS) on sitagliptin, the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus-Thrombolysis in Myocardial Infarction (SAVOR-TIMI) 53 trial on saxagliptin, the Cardiovascular Outcomes Study of Alogliptin in Subjects With Type 2 Diabetes and Acute Coronary Syndrome (EXAMINE) trial on alogliptin, and the Cardiovascular Outcome

  13. Are Inflammatory and Coagulation Biomarkers Related to Sleep Characteristics in Mid-Life Women?: Study of Women's Health Across the Nation Sleep Study

    Science.gov (United States)

    Matthews, Karen A.; Zheng, Huiyong; Kravitz, Howard M.; Sowers, MaryFran; Bromberger, Joyce T.; Buysse, Daniel J.; Owens, Jane F.; Sanders, Mark; Hall, Martica

    2010-01-01

    Study Objectives: Inflammation and pro-coagulation biomarkers may be a link between sleep characteristics and risk for cardiometabolic disorders. We tested the hypothesis that worse sleep characteristics would be associated with C-reactive protein (CRP), fibrinogen, factor VIIc, and plasminogen activator inhibitor (PAI)-1 in a multi-ethnic subsample of mid-life women enrolled in the Study of Women's Health across the Nation. Design: Cross-sectional. Measurements and Results: African American, Chinese, and Caucasian women (N = 340) participated in 3 days of in-home polysomnographic (PSG) monitoring and had measures of inflammation and coagulation. Regression analyses revealed that each of the biomarkers were associated with indicators of sleep disordered breathing after adjusting for age, duration between sleep study and blood draw, site, menopausal status, ethnicity, residualized body mass index, smoking status, and medications that affect sleep or biomarkers. Among African American women, those who had higher levels of CRP had shorter PSG-sleep duration and those who had higher levels of fibrinogen had less efficient sleep in multivariate models. Conclusions: These results suggest that inflammation and pro-coagulation processes may be an important pathway connecting sleep disordered breathing and cardiometabolic disorders in women of these ethnic groups and that inflammation may be a particularly important pathway in African Americans. Citation: Matthews KA; Zheng H; Kravitz HM; Sowers M; Bromberger JT; Buysse DJ; Owens JF; Sanders M; Hall M. Are inflammatory and coagulation biomarkers related to sleep characteristics in mid-life women?: Study of Women's Health Across the Nation Sleep Study. SLEEP 2010;33(12):1649-1655. PMID:21120127

  14. 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

    ) 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...

  15. Distinct Roles of Ser-764 and Lys-773 at the N Terminus of von Willebrand Factor in Complex Assembly with Coagulation Factor VIII*

    Science.gov (United States)

    Castro-Núñez, Lydia; Bloem, Esther; Boon-Spijker, Mariëtte G.; van der Zwaan, Carmen; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B.

    2013-01-01

    Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766–Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764–Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism. PMID:23168412

  16. Distinct roles of Ser-764 and Lys-773 at the N terminus of von Willebrand factor in complex assembly with coagulation factor VIII.

    Science.gov (United States)

    Castro-Núñez, Lydia; Bloem, Esther; Boon-Spijker, Mariëtte G; van der Zwaan, Carmen; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B

    2013-01-01

    Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766-Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764-Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism. PMID:23168412

  17. 晚期血吸虫病肝硬化患者凝血功能检测分析%Analysis of blood coagulation function in patients with cirrhosis due to advanced schistosomiasis

    Institute of Scientific and Technical Information of China (English)

    牛长生; 余永辉

    2014-01-01

    Objective To detect the indexes of blood coagulation in patients with advanced schistosomiasis (AS) compared with chronic schistosomiasis (CS), probe its coagulation mechanism, monitor the bleeding tendency timely and provide basis for clinical treatment. Methods Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of 37 patients with AS and 80 with CS were detected by Rayto RT-2204C coagulation analyzer. Results PT, APTT and TT of patients with AS were obvious higher than patients with CS(P<0.01). Conclusion The blood coagulation function of patients with AS is obvious abnormal. Detecting the indexes of blood coagulation is significant to monitoring the bleeding tendency and instructing the clinical medication for patients with AS.%目的:对比检测晚期血吸虫病与慢性血吸虫病患者的凝血指标,探讨晚血病人的凝血功能机制,及时监测晚血病人的出血倾向并为临床指导用药提供依据。方法运用国产雷杜RT-2204C血凝仪检测37例晚血病人和80例慢血病人的血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)和凝血酶时间(TT)。结果晚血病人PT、APTT和TT值均大于慢血病人,差异有统计学意义(P均<0.01)。结论晚血患者凝血功能明显异常,处于低凝状态且纤溶系统受损,检测该指标对监测晚血病人出血倾向与指导临床用药具有重要的意义。

  18. A structural locus for coagulation factor XIIIA (F13A) is located distal to the HLA region on chromosome 6p in man.

    Science.gov (United States)

    Olaisen, B; Gedde-Dahl, T; Teisberg, P; Thorsby, E; Siverts, A; Jonassen, R; Wilhelmy, M C

    1985-01-01

    Linkage between the locus for coagulation factor XIIIA (F13A) and HLA-region genes has been revealed during a linkage study between F13A and approximately 40 other polymorphic marker genes. In males, the maximum lod score between F13A and HLA-region genes (HLA-A, -C, -B, -DR; C4A, -B; Bf; and/or C2) is 7.60 at theta 1 = .18. To GLO, the maximum lod score is 2.37 at theta 1 = .19; to PGM3, .22 at theta 1 = .35. Female data indicate a clear sex difference in recombination frequency between F13A and HLA. The present findings, in combination with earlier knowledge of PGM3/GLO/HLA localization and gene distances, show that F13A is distal to HLA on the short arm of chromosome 6 in man. It is thus likely that by including FXIIIA typing in linkage studies, the whole male 6p is within mapping distance of highly polymorphic, classical marker genes. Earlier findings that the Hageman factor gene (F12) is located in the same chromosomal region may indicate the presence of a coagulation factor gene cluster in this region.

  19. Incidence and risk factors of occupational blood exposure

    DEFF Research Database (Denmark)

    Nelsing, S; Nielsen, T L; Brønnum-Hansen, Henrik;

    1997-01-01

    .6-3.1 PCE/pry and 6.0-6.9 MCE/pry). Finally Pathology, Internal medicine, Radiology and Paediatrics had a considerable risk (0.8-1.3 PCE/pry and 1.3-2.9 MCE/pry). Potential risk factors were examined by Poisson regression. Employment as senior as compared to junior doctor was associated with a higher risk......). Only 35% adhered to the basic principles of universal precautions (UP) and non-compliance was associated with a considerably increased risk of both MCE and PCE, especially in non-surgical specialties. In conclusion, we found an unacceptably high incidence of occupational blood exposures among Danish......Occupational blood exposures involves a risk of transmission of serious infections. We performed a nation-wide survey, to describe the incidence and risk factors of percutaneous (PCE) and mucocutaneous (MCE) blood exposures among hospital employed doctors in Denmark. Of 9,374 questionnaires, 6...

  20. The Interface between Inflammation and Coagulation in Cardiovascular Disease

    OpenAIRE

    Gabriele Demetz; Ilka Ott

    2012-01-01

    The intimate connection between coagulation and inflammation in the pathogenesis of vascular disease has moved more and more into focus of clinical research. This paper focuses on the essential components of this interplay in the settings of cardiovascular disease and acute coronary syndrome. Tissue factor, the main initiator of the extrinsic coagulation pathway, plays a central role via causing a proinflammatory response through activation of coagulation factors and thereby initiating coagul...

  1. Predicting Blood Transfusion Factors in Coronary Artery Bypass Surgery

    Directory of Open Access Journals (Sweden)

    L. Kasraian

    2007-04-01

    Full Text Available Introduction & Objective: The ability to predict the use of blood components during bypass surgery will improve the blood banks ability to provide efficient service.Materials and Methods: This is a retrospective cross-sectional study that was carried out on patients that underwent CABG in Shiraz Namazi hospital in 2004. The sample size was 480 and we did systematic random sampling, and a questionnaire contained factors that effect on blood need was filling out. Independent t-test, multivariate logistic regression and Poason correlation were used for data analysis.Results: The average age of patients was 59.15±10.6 years, 69.2% were male and the mean Hct before surgery was 39.86±6.38% and after operation was 32.68±5.84% and the duration of surgery was 2 hours and 48 minutes. The average of pack cell was 5.76±1.52 unit and average of FFP was 2.82±7.72 unit. There was not significant correlation between ages, weighs, Hct before and after, sex and pack cell use (P> 0.05. The use of pack cell and FFP were more in urgent surgery in diabetic patients and vascular disease (P< 0.05.Conclusion: It seems that the rate of blood demanding in proportion to blood use is logical but the rate of blood usage is more than blood usage in other countries with considering of immunological and non-immunological complication of blood products, the heart surgeons must do special concern about the making decision for blood use.

  2. Successful immune tolerance induction with low-dose coagulation factor VIII in a patient with hemophilia A from a developing country.

    Science.gov (United States)

    Ay, Yilmaz; Ersin, Toret; Yesim, Oymak; Hilkay, Karapinar Tuba; Dilek, Ince; Gulcihan, Ozek; Ahmet, Koc

    2016-09-01

    Inhibitor development is the most frequent and serious complication of the treatment in patients with hemophilia. Immune tolerance induction (ITI) is the only option of treatment for the eradication of factor VIII (FVIII) inhibitor. We would like to present our case with hemophilia whose FVIII inhibitor eradication was done by a low-dose ITI regimen. Our patient has been applied on-demand therapy until 8 years of age. Secondary prophylaxis was began because of having hemophilic arthropathy. A low titer of FVIII inhibitor (4.2 BU/ml) was detected in the fifth month of the prophylaxis. The peak inhibitor titer of patient was 4.6 BU/ml, and there was no decrease in inhibitor titer in the follow-up duration. The low-dose ITI (50 IU/kg, 3 days a week) was started. His inhibitor level was detected negative and the recovery test was ameliorated in the 15th of the ITI therapy. High-dose regimen ITI could not be given particularly in developing countries such as Turkey in view of the high cost of treatment. Patients who had good risk factors might be successfully treated by using low-dose ITI regimen as effective as high-dose ITI regimen. PMID:26484639

  3. Reduction of Factor VIII Inhibitor Titers During Immune Tolerance Induction With Recombinant Factor VIII-Fc Fusion Protein.

    Science.gov (United States)

    Groomes, Charles L; Gianferante, David M; Crouch, Gary D; Parekh, Dina S; Scott, David W; Lieuw, Kenneth

    2016-05-01

    The development of inhibitors toward factor VIII (FVIII) is a common and serious complication of hemophilia A (HA) therapy. Patients with hemophilia who develop inhibitors often undergo time- and resource-intensive immune tolerance induction (ITI) protocols. We report a 15-month-old male with severe HA and a high-titer inhibitor that occurred while receiving prophylactic treatment with recombinant FVIII (rFVIII), in whom significant inhibitor titer reduction was achieved with thrice weekly infusions of a new, prolonged half-life rFVIII-Fc fusion protein product (trade name Eloctate). Further studies are warranted to explore the potential of Eloctate in ITI protocols. PMID:26739399

  4. Factors Associated with Repeat Blood Donation at the Northern Zone Blood Transfusion Centre in Tanzania

    Directory of Open Access Journals (Sweden)

    Wilhellmuss I. Mauka

    2015-01-01

    Full Text Available Background and Objective. The aim of this study was to determine factors associated with repeat blood donation. Methods. This was a cross-sectional study carried out among blood donors aged 18–65 years in northern Tanzania. The questionnaire was administered among 454 participants through the phone. Results. Of the 454 participants, the proportion of repeat donation was 63.9%. In the backward logistic regression analysis, the significant predictors were living in Arusha which had lower odds of repeat donation compared to those living in Kilimanjaro. Knowledge of time interval between donations increased odds of repeating donations. High intention increased odds of repeat donation compared to low intention. Altruistic score had minor effect on increasing odds of repeating donation. Conclusion. Repeat blood donation is affected by proximity of donating site, awareness of the blood donation interval, intention to donate, and experience on previous donation. We recommend continuous education concerning blood donors and donation among health workers and society as a whole; this will create awareness on motivational factors for repeat donations.

  5. Soluble vascular endothelial growth factor in various blood transfusion components

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Werther, K; Mynster, T;

    1999-01-01

    of platelet-derived soluble plasminogen activator inhibitor type 1 (sPAI-1) was determined by an EIA in the same samples. Finally, the extracellular accumulation of sVEGF was determined in nonfiltered WB and SAGM blood during storage for 35 days and in BCP pools during storage for 7 days. RESULTS: In...... the healthy volunteers, median total sVEGF content was 97 (range, 20-303) pg per mL in serum and 19 (13-37) pg per mL in plasma (n = 12, p < 0.002) and 445 (280-990) pg per mL in lysed cells. Median total sPAI-1 content was 94 (64-127) ng per mL in serum, 8 (6-11) ng per mL in citrated plasma, and 95...

  6. Attach importance to the early diagnosis and treatment of acute coagulation dysfunction after major war trauma

    OpenAIRE

    Li, Jie-Shou; Li, You-sheng

    2013-01-01

    Coagulation dysfunction after major war trauma is conventionally attributed to consumption and dilution of coagulation factors. However, recent studies have identified an acute coagulation dysfunction at the early stage after trauma. This coagulation dysfunction due to endogenous coagulation disturbance at the early stage after trauma is called acute traumatic coagulation dysfunction (ATCD), and the patients with ATCD would have an increased complication rate and mortality. Standard coagulati...

  7. 铝盐混凝除砷影响因素及机制研究%Influencing Factors and Mechanism of Arsenic Removal During the Aluminum Coagulation Process

    Institute of Scientific and Technical Information of China (English)

    陈桂霞; 胡承志; 朱灵峰; 童华卿

    2013-01-01

    Aluminum coagulants are widely used in arsenic (As) removal during the drinking water treatment process. Aluminium chloride ( A1C13) and polyaluminium chloride (PAC1) which contains high content of Al13 were used as coagulants. The effects of aluminum species, pH, humic acid (HA) and coexisting anions on arsenic removal were investigated. Results showed that A1C13 and PAC1 were almost ineffective in As(Ⅲ) removal while the As( V ) removal efficiency reached almost 100% . pH was an important influencing factor on the arsenic removal efficiency, because pH influenced the distribution of aluminum species during the coagulation process. The efficiency of arsenic removal by aluminum coagulants was positively correlated with the content of Al13 species. HA and some coexisting anions showed negative impact on arsenic removal because of the competitive adsorption. The negative influence of HA was more pronounced at low coagulant dosages. PO43- and F- showed marked influence during arsenic removal, but there was no obvious influence when SiO32- , CO32- and SO42- coexisted. The present study would be helpful to direct arsenic removal by enhanced coagulation during the drinking water treatment.%铝盐混凝法被广泛应用于饮用水除砷工程.本研究选取三氯化铝(AlCl3)和富含Al13的聚合氯化铝(PACl)为絮凝剂,考察铝形态、pH值、腐殖酸(HA)以及共存阴离子对砷去除的影响与机制.结果表明,2种絮凝剂对As(Ⅲ)去除效能较低,对As(Ⅴ)去除率可达到近100%.pH影响混凝过程中铝形态分布,从而对铝盐混凝除砷效能产生重要影响.铝盐除砷效能与混凝过程中的Al13形态含量呈正相关关系.由于竞争吸附作用,HA和部分共存阴离子对砷的混凝去除产生负面影响.HA对混凝效能影响与絮凝剂投药量相关,投药量越低,则影响越大.PO43-和F-对混凝除砷效能影响显著,SiO32-、CO32-和SO42-对混凝除砷效能影响较小.本研究将对饮用水强化

  8. Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors.

    Directory of Open Access Journals (Sweden)

    Pavla Fajtová

    Full Text Available Blood flukes of the genus Schistosoma cause schistosomiasis, a parasitic disease that infects over 240 million people worldwide, and for which there is a need to identify new targets for chemotherapeutic interventions. Our research is focused on Schistosoma mansoni prolyl oligopeptidase (SmPOP from the serine peptidase family S9, which has not been investigated in detail in trematodes.We demonstrate that SmPOP is expressed in adult worms and schistosomula in an enzymatically active form. By immunofluorescence microscopy, SmPOP is localized in the tegument and parenchyma of both developmental stages. Recombinant SmPOP was produced in Escherichia coli and its active site specificity investigated using synthetic substrate and inhibitor libraries, and by homology modeling. SmPOP is a true oligopeptidase that hydrolyzes peptide (but not protein substrates with a strict specificity for Pro at P1. The inhibition profile is analogous to those for mammalian POPs. Both the recombinant enzyme and live worms cleave host vasoregulatory, proline-containing hormones such as angiotensin I and bradykinin. Finally, we designed nanomolar inhibitors of SmPOP that induce deleterious phenotypes in cultured schistosomes.We provide the first localization and functional analysis of SmPOP together with chemical tools for measuring its activity. We briefly discuss the notion that SmPOP, operating at the host-parasite interface to cleave host bioactive peptides, may contribute to the survival of the parasite. If substantiated, SmPOP could be a new target for the development of anti-schistosomal drugs.

  9. Src and PI3 K inhibitors affect the virulence factors of Entamoeba histolytica.

    Science.gov (United States)

    López-Contreras, L; Hernández-Ramírez, V I; Flores-García, Y; Chávez-Munguía, B; Talamás-Rohana, P

    2013-02-01

    Protein kinases (PKs) of parasitic protozoa are being evaluated as drug targets. A large number of protein kinases within the protein kinome of Entamoeba histolytica strongly suggest that protein phosphorylation is a key component of pathogenesis regulation by this parasite. PI3 K and Src are kinases previously described in this parasite, but their role is poorly understood. Here, the effect of Src-1-inhibitor and PI3 K inhibitor (Wortmannin) on the virulence factors of E. histolytica was evaluated. Results show that both inhibitors affect the actin cytoskeleton and the amoebic movement. Also, the proteolytic activity is diminished by Wortmannin, but not by Src-inhibitor-1; however, the phagocytic capacity is diminished by Wortmannin and Src-1-inhibitor. Finally, we found that the virulence in vivo of E. histolytica is affected by Wortmannin but not by Src-1-inhibitor. This study opens the way for the design of anti-amoebic drugs based on kinase inhibition.

  10. Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation

    International Nuclear Information System (INIS)

    Sulfur mustard (SM) inhalation causes airway injury, with enhanced vascular permeability, coagulation, and airway obstruction. The objective of this study was to determine whether recombinant tissue factor pathway inhibitor (TFPI) could inhibit this pathogenic sequence. Methods: Rats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5 mg/kg) in vehicle, or vehicle alone, was instilled into the trachea. Arterial O2 saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma were analyzed for prothrombin, thrombin–antithrombin complex (TAT), active plasminogen activator inhibitor-1 (PAI-1) levels, and fluid fibrinolytic capacity. Lung steady-state PAI-1 mRNA was measured by RT-PCR analysis. Airway-capillary leak was estimated by BALF protein and IgM, and by pleural fluid measurement. In additional animals, airway cast formation was assessed by microdissection and immunohistochemical detection of airway fibrin. Results: Airway obstruction in the form of fibrin-containing casts was evident in central conducting airways of rats receiving CEES. TFPI decreased cast formation, and limited severe hypoxemia. Findings of reduced prothrombin consumption, and lower TAT complexes in BALF, demonstrated that TFPI acted to limit thrombin activation in airways. TFPI, however, did not appreciably affect CEES-induced airway protein leak, PAI-1 mRNA induction, or inhibition of the fibrinolytic activity present in airway surface liquid. Conclusions: Intratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury. - Highlights: • TFPI administration to rats after mustard inhalation reduces airway cast formation. • Inhibition of thrombin activation is the likely mechanism for limiting casts. • Rats given TFPI had

  11. Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

    Directory of Open Access Journals (Sweden)

    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

  12. Perinatal factors associated with blood pressure during childhood.

    Science.gov (United States)

    Bergel, E; Haelterman, E; Belizán, J; Villar, J; Carroli, G

    2000-03-15

    This study aims to determine whether variables reflecting an adverse intrauterine environment are associated with childhood blood pressure. The authors conducted a secondary analysis of data from a prospective cohort of children born to healthy, nulliparous women enrolled in a randomized controlled trial. A total of 518 children were traced in 1995-1996 from 614 eligible children born in a clinic in Rosario, Argentina. The outcome was systolic blood pressure at 5-9 years. Hemoglobin during pregnancy was positively associated with children's pressure. Other maternal characteristics during pregnancy (blood pressure, smoking, weight gain, weight at 20 weeks' gestation, and glycemia) and size at birth (birth weight, ponderal index, head circumference/length ratio, and small for gestational age) were not associated with children's pressure. Among children in the upper quartile of body mass index, there was a weak inverse correlation between birth weight and systolic pressure, and systolic pressure was 14.8 mmHg (95 percent confidence interval: 3.3, 26.4) higher in low birth weight children than in others. The main predictors of childhood pressure were childhood body mass index and maternal pressure outside pregnancy. In this healthy population, the authors found weak support for an association between variables reflecting an adverse fetal environment and childhood blood pressure. Low birth weight was a risk factor for high blood pressure only in overweight children. PMID:10733041

  13. Effects of nucleotides and nucleosides on coagulation

    DEFF Research Database (Denmark)

    Bune, Laurids; Thaning, Pia; Johansson, Pär I;

    2010-01-01

    Nucleotides, including ADP, ATP and uridine triphosphate (UTP), are discharged profusely in the circulation during many pathological conditions including sepsis. Sepsis can cause hypotension and systemic activation of the coagulation and fibrinolytic systems in humans, which may cause disseminated...... intravascular coagulation. We investigated whether nucleotide-induced cardiovascular collapse as provoked by systemic infusion of adenosine, ADP, ATP, UTP and nitric oxide affected the haemostatic system as assessed by whole blood thromboelastography (TEG) analysis. Ten pigs received a randomized infusion...

  14. Inflammation and coagulation

    NARCIS (Netherlands)

    M. Levi; T. van der Poll

    2010-01-01

    In the pathogenesis of sepsis, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation leads to activation of coagulation, and coagulation also considerably affects inflammatory activity. Molecular pathwa

  15. Human inter-α-inhibitor is a substrate for factor XIIIa and tissue transglutaminase

    DEFF Research Database (Denmark)

    Sonne-Schmidt, Carsten Scavenius; Sanggaard, Kristian W; Nikolajsen, Camilla L;

    2011-01-01

    that inter-α-inhibitor is cross-linked to the fibrin clot in a 1:20 ratio relative to the known factor XIIIa substrate α2-antiplasmin. This interaction may protect fibrin or other Lys-donating proteins from adventitious proteolysis by increasing the local concentration of bikunin. In addition, the reaction......In this study, we show that inter-α-inhibitor is a substrate for both factor XIIIa and tissue transglutaminase. These enzymes catalyze the incorporation of dansylcadaverine and biotin-pentylamine, revealing that inter-α-inhibitor contains reactive Gln residues within all three subunits...

  16. Small molecule ice recrystallization inhibitors mitigate red blood cell lysis during freezing, transient warming and thawing

    Science.gov (United States)

    Briard, Jennie G.; Poisson, Jessica S.; Turner, Tracey R.; Capicciotti, Chantelle J.; Acker, Jason P.; Ben, Robert N.

    2016-03-01

    During cryopreservation, ice recrystallization is a major cause of cellular damage. Conventional cryoprotectants such as dimethyl sulfoxide (DMSO) and glycerol function by a number of different mechanisms but do not mitigate or control ice recrystallization at concentrations utilized in cryopreservation procedures. In North America, cryopreservation of human red blood cells (RBCs) utilizes high concentrations of glycerol. RBC units frozen under these conditions must be subjected to a time-consuming deglycerolization process after thawing in order to remove the glycerol to <1% prior to transfusion thus limiting the use of frozen RBC units in emergency situations. We have identified several low molecular mass ice recrystallization inhibitors (IRIs) that are effective cryoprotectants for human RBCs, resulting in 70–80% intact RBCs using only 15% glycerol and slow freezing rates. These compounds are capable of reducing the average ice crystal size of extracellular ice relative to a 15% glycerol control validating the positive correlation between a reduction in ice crystal size and increased post-thaw recovery of RBCs. The most potent IRI from this study is also capable of protecting frozen RBCs against the large temperature fluctuations associated with transient warming.

  17. Small molecule ice recrystallization inhibitors enable freezing of human red blood cells with reduced glycerol concentrations.

    Science.gov (United States)

    Capicciotti, Chantelle J; Kurach, Jayme D R; Turner, Tracey R; Mancini, Ross S; Acker, Jason P; Ben, Robert N

    2015-01-01

    In North America, red blood cells (RBCs) are cryopreserved in a clinical setting using high glycerol concentrations (40% w/v) with slow cooling rates (~1°C/min) prior to storage at -80°C, while European protocols use reduced glycerol concentrations with rapid freezing rates. After thawing and prior to transfusion, glycerol must be removed to avoid intravascular hemolysis. This is a time consuming process requiring specialized equipment. Small molecule ice recrystallization inhibitors (IRIs) such as β-PMP-Glc and β-pBrPh-Glc have the ability to prevent ice recrystallization, a process that contributes to cellular injury and decreased cell viability after cryopreservation. Herein, we report that addition of 110 mM β-PMP-Glc or 30 mM β-pBrPh-Glc to a 15% glycerol solution increases post-thaw RBC integrity by 30-50% using slow cooling rates and emphasize the potential of small molecule IRIs for the preservation of cells.

  18. Small molecule ice recrystallization inhibitors mitigate red blood cell lysis during freezing, transient warming and thawing.

    Science.gov (United States)

    Briard, Jennie G; Poisson, Jessica S; Turner, Tracey R; Capicciotti, Chantelle J; Acker, Jason P; Ben, Robert N

    2016-01-01

    During cryopreservation, ice recrystallization is a major cause of cellular damage. Conventional cryoprotectants such as dimethyl sulfoxide (DMSO) and glycerol function by a number of different mechanisms but do not mitigate or control ice recrystallization at concentrations utilized in cryopreservation procedures. In North America, cryopreservation of human red blood cells (RBCs) utilizes high concentrations of glycerol. RBC units frozen under these conditions must be subjected to a time-consuming deglycerolization process after thawing in order to remove the glycerol to recrystallization inhibitors (IRIs) that are effective cryoprotectants for human RBCs, resulting in 70-80% intact RBCs using only 15% glycerol and slow freezing rates. These compounds are capable of reducing the average ice crystal size of extracellular ice relative to a 15% glycerol control validating the positive correlation between a reduction in ice crystal size and increased post-thaw recovery of RBCs. The most potent IRI from this study is also capable of protecting frozen RBCs against the large temperature fluctuations associated with transient warming.

  19. Surgery as a risk factor for inhibitor development in haemophilia A : A systematic review

    NARCIS (Netherlands)

    Eckhardt, C.; Van Der Bom, J.; Van Der Naald, M.; Peters, M.; Kamphuisen, P.; Fijnvandraat, K.

    2010-01-01

    Introduction: Surgery is a risk factor for the development of factor VIII inhibiting antibodies (inhibitors) in haemophilia A. This may be due to the combination of danger signal release resulting from tissue damage and intensive exposure to factor VIII (FVIII) concentrate. The purpose of this syste

  20. 丹红注射液对严重脓毒症凝血功能及预后的影响%Effect of Danhong Injection on Severe Sepsis Blood Coagulation Function and Prognosis

    Institute of Scientific and Technical Information of China (English)

    李志云; 杜仲平; 王春雨; 王恩燕; 戴坤鹏; 王滨; 白桦

    2015-01-01

    目的:探讨丹红注射液对严重脓毒症患者凝血功能及血乳酸的影响。方法:选择重症医学科收治的严重脓毒症患者100例,随机分为治疗组(n =52)和对照组(n =48),2组患者入院开始即给予充分的液体复苏、积极的抗感染治疗,必要时予血管活性药物、选择性的给予氢化可的松、呼吸机辅助通气等支持治疗,治疗组加用丹红注射液40 mL 静脉滴注,1次/d。2组患者在入院时及入院第7天时监测急性生理学及慢性健康状况评分(APACHE Ⅱ评分)、凝血指标及血乳酸水平,并监测患者28 d 死亡率。结果:2组患者入院第7天的凝血指标、血乳酸(Blood Lactic Acid,BLA)及 APACHE Ⅱ评分比较均有统计学意义(P <0.05);患者28天死亡率治疗组比对照组低,但差异无统计学意义(P >0.05)。结论:丹红注射液可改善严重脓毒症患者凝血状态及低灌注缺氧代谢。%Objective:To observe the effect of Danhong injection on blood coagulation function and blood lactic acid in patients with severe sepsis.Methods:A hundred patients with severe sepsis from the Intesive Care Unite were randomly classified into treat-ment group(n =52)and control group(n =48).Patients in both groups were treated with fluid resuscitation,anti infection drugs at admission and given the vasoactive drug,hydrocortisone and mechanical ventilation support when necessary.The treatment group was treated with Danhong injection intravenous infusion of 40 mL once a day.APACHE Ⅱscore,blood coagulation indexes and blood lactic acid were measured at admission and the seventh day of hospitalization.The mortality was monitored at the 28th day of hospitalization.Results:The blood coagulation indexes,blood lactic acid and APACHE Ⅱscore of the treatment group and the control group were of significant difference at the seventh day(P 0.05).Conclusion:Danhong injection can improve the blood

  1. Adverse Reaction to Cetuximab, an Epidermal Growth Factor Receptor Inhibitor.

    Science.gov (United States)

    Štulhofer Buzina, Daška; Martinac, Ivana; Ledić Drvar, Daniela; Čeović, Romana; Bilić, Ivan; Marinović, Branka

    2016-04-01

    Dear Editor, Inhibition of the epidermal growth factor receptor (EGFR) is a new strategy in treatment of a variety of solid tumors, such as colorectal carcinoma, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and pancreatic cancer (1). Cetuximab is a chimeric human-murine monoclonal antibody against EGFR. Cutaneous side effects are the most common adverse reactions occurring during epidermal growth factor receptor inhibitors (EGFRI) therapy. Papulopustular rash (acne like rash) develop with 80-86% patients receiving cetuximab, while xerosis, eczema, fissures, teleangiectasiae, hyperpigmentations, and nail and hair changes occur less frequently (2). The mechanism underlying these skin changes has not been established and understood. It seems EGFRI alter cell growth and differentiation, leading to impaired stratum corneum and cell apoptosis (3-5). An abdominoperineal resection of the rectal adenocarcinoma (Dukes C) was performed on a 43-year-old female patient. Following surgery, adjuvant chemo-radiotherapy was applied. After two years, the patient suffered a metastatic relapse. Abdominal lymphadenopathy was detected on multi-slice computer tomography (MSCT) images, with an increased value of the carcinoembryonic antigen (CEA) tumor marker (maximal value 57 ng/mL). Hematological and biochemical tests were within normal limits, so first-line chemotherapy with oxaliplatin and a 5-fluorouracil (FOLFOX4) protocol was introduced. A wild type of the KRAS gene was confirmed in tumor tissue (diagnostic prerequisite for the introduction of EGFRI) and cetuximab (250 mg per m2 of body surface) was added to the treatment protocol. The patient responded well to the treatment with confirmed partial regression of the tumor formations. Three months after the patient started using cetuximab, an anti-EGFR monoclonal antibody, the patient presented with a papulopustular eruption in the seborrhoeic areas (Figure 1) and eczematoid reactions on the extremities

  2. Micronutrients attenuate progression of prostate cancer by elevating the endogenous inhibitor of angiogenesis, Platelet Factor-4

    International Nuclear Information System (INIS)

    Longstanding evidence implicates an inadequate diet as a key factor in the onset and progression of prostate cancer. The purpose herein was to discover, validate and characterize functional biomarkers of dietary supplementation capable of suppressing the course of prostate cancer in vivo. The Lady transgenic mouse model that spontaneously develops prostate cancer received a diet supplemented with a micronutrient cocktail of vitamin E, selenium and lycopene ad libitum. A proteomic analysis was conducted to screen for serum biomarkers of this dietary supplementation. Candidate peptides were validated and identified by sequencing and analyzed for their presence within the prostates of all mice by immunohistochemistry. Dietary supplementation with the combined micronutrients significantly induced the expression of the megakaryocyte-specific inhibitor of angiogenesis, platelet factor-4 (P = 0.0025). This observation was made predominantly in mice lacking tumors and any manifestations associated with progressive disease beyond 37 weeks of life, at which time no survivors remained in the control group (P < 0.0001). While prostates of mice receiving standard chow were enlarged and burdened with poorly differentiated carcinoma, those of mice on the supplemented diet appeared normal. Immunohistochemical analysis revealed marked amplifications of both platelet binding and platelet factor-4 within the blood vessels of prostates from mice receiving micronutrients only. We present unprecedented data whereby these combined micronutrients effectively promotes tumor dormancy in early prostate cancer, following initiation mutations that may drive the angiogenesis-dependent response of the tumor, by inducing platelet factor-4 expression and concentrating it at the tumor endothelium through enhanced platelet binding

  3. Development of a novel tricyclic class of potent and selective FIXa inhibitors.

    Science.gov (United States)

    Meng, Dongfang; Andre, Patrick; Bateman, Thomas J; Berger, Richard; Chen, Yi-Heng; Desai, Kunal; Dewnani, Sunita; Ellsworth, Kenneth; Feng, Daming; Geissler, Wayne M; Guo, Liangqin; Hruza, Alan; Jian, Tianying; Li, Hong; Metzger, Joe; Parker, Dann L; Reichert, Paul; Sherer, Edward C; Smith, Cameron J; Sonatore, Lisa M; Tschirret-Guth, Richard; Wu, Jane; Xu, Jiayi; Zhang, Ting; Campeau, Louis-Charles; Orr, Robert; Poirier, Marc; McCabe-Dunn, Jamie; Araki, Kazuto; Nishimura, Teruyuki; Sakurada, Isao; Hirabayashi, Tomokazu; Wood, Harold B

    2015-11-15

    Using structure based drug design, a novel class of potent coagulation factor IXa (FIXa) inhibitors was designed and synthesized. High selectivity over FXa inhibition was achieved. Selected compounds were evaluated in rat IV/PO pharmacokinetic (PK) studies and demonstrated desirable oral PK profiles. Finally, the pharmacodynamics (PD) of this class of molecules were evaluated in thrombin generation assay (TGA) in Corn Trypsin Inhibitor (CTI) citrated human plasma and demonstrated characteristics of a FIXa inhibitor. PMID:26318999

  4. Development of a novel class of potent and selective FIXa inhibitors.

    Science.gov (United States)

    Zhang, Ting; Andre, Patrick; Bateman, Thomas J; Chen, Yi-Heng; Desai, Kunal; Ellsworth, Kenneth; Geissler, Wayne M; Guo, Liangqin; Hruza, Alan; Jian, Tianying; Meng, Dongfang; Parker, Dann L; Qian, Xiaoxia; Reichert, Paul; Sherer, Edward C; Shu, Min; Smith, Cameron J; Sonatore, Lisa M; Tschirret-Guth, Richard; Nolting, Andrew F; Orr, Robert; Campeau, Louis-Charles; Araki, Kazuto; Nishimura, Teruyuki; Sakurada, Isao; Wood, Harold B

    2015-11-01

    Using structure based drug design (SBDD), a novel class of potent coagulation Factor IXa (FIXa) inhibitors was designed and synthesized. High selectivity over FXa inhibition was achieved. Selected compounds demonstrated oral bioavailability in rat IV/PO pharmacokinetic (PK) studies. Finally, the pharmacodynamics (PD) of this class of molecules was evaluated in Thrombin Generation Assay (TGA) in Corn Trypsin Inhibitor (CTI) citrated human plasma and demonstrated characteristics of a FIXa inhibitor. PMID:25978966

  5. Modification of a commercial thromboelastography instrument to measure coagulation dynamics with three-dimensional biomaterials.

    Science.gov (United States)

    Hawker, Morgan J; Olver, Christine S; Fisher, Ellen R

    2016-06-01

    Three-dimensional synthetic constructs with complex geometries have immense potential for use in a multitude of blood-contacting applications. Understanding coagulation phenomena is arguably the most critical aspect for applications involving synthetic biomaterials; however, real-time evaluation of the clot formation while interfacing with these materials is difficult to achieve in a reproducible and robust manner. Here, work representing first steps toward addressing this deficit is presented, wherein modified consumables for a clinical instrument (a Thromboelastograph(®)) have been fabricated. Thromboelastography (TEG) measures viscoelastic properties throughout clot formation and therefore provides clinically relevant coagulation measurements in real time (i.e., kinetics and strength of clot formation). Through our modification, TEG consumables can readily accommodate three-dimensional materials (e.g., those for regenerative tissue applications). The authors performed proof-of-concept experiments using polymer scaffolds with a range of surface properties and demonstrated that variations in surface properties resulted in differences in blood plasma coagulation dynamics. For example, the maximum rate of thrombus generation ranged from 22.2 ± 2.2 (dyn/cm(2))/s for fluorocarbon coated scaffolds to 8.7 ± 1.0 (dyn/cm(2))/s for nitrogen-containing scaffolds. Through this work, the ability to make real-time coagulation activity measurements during constant coagulation factor interface with biomedically relevant materials is demonstrated. PMID:27126596

  6. Anopheles midgut epithelium evades human complement activity by capturing factor H from the blood meal.

    Directory of Open Access Journals (Sweden)

    Ayman Khattab

    2015-02-01

    Full Text Available Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood.

  7. Antibody response to recombinant human coagulation factor VIII in a new rat model of severe hemophilia A

    DEFF Research Database (Denmark)

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

    2016-01-01

    Background: Neutralizing antibodies towardFVIII replacement therapy (inhibitors) are the most seri-ous treatment-related complication in hemophilia A(HA). A rat model of severe HA (F8/) has recentlybeen developed, but an immunological characterization isneeded to determine the value of using...

  8. (S)YS-51, a novel isoquinoline alkaloid, attenuates obesity-associated non-alcoholic fatty liver disease in mice by suppressing lipogenesis, inflammation and coagulation.

    Science.gov (United States)

    Park, Eun Jung; Kim, Young Min; Kim, Hye Jung; Jang, Se-Yun; Oh, Moo Hyun; Lee, Duck-Hyung; Chang, Ki Churl

    2016-10-01

    Obesity-associated non-alcoholic fatty liver disease (NAFLD) increases coagulation and inflammation. We hypothesized that (S)YS-51, an agent found to be beneficial in animal models of sepsis, may reduce NAFLD in high-fat diet (HFD) mice by reducing coagulation and inflammation. C57BL/6 mice were fed either a chow diet or HFD and each was supplemented with or without (S)YS-51 (10mg/kg, daily, i.p.) for 16 weeks. The results showed that HFD caused significant increases in lipogenesis [CD36, fatty acid synthase (FAS) and sterol response element binding protein (SREBP)-1c mRNA and protein], inflammation [monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α, intercellular cell adhesion molecule-1 (ICAM-1), TGF-β, and procollagen type 1 mRNA, macrophage infiltration] and coagulation [tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) mRNA and thrombin antithrombin complex (TAT)] in the liver, adipose tissue and serum, which were significantly reduced by (S)YS-51. These results of (S)YS-51 were accompanied by significant reduction of weight gain, liver size, hepatic steatosis and fibrosis, blood cholesterol, hepatic triglyceride, and macrophage infiltration and inflammatory cytokines in adipose tissue without affecting food intake in HFD mice. Interestingly, (S)YS-51 increased SIRT1 mRNA and protein and AMPK expression in the liver of HFD mice by increasing both NAD(+)/NADH ratio and LKB1 phosphorylation. In HepG2 cells, (S)YS-51 activated SIRT1 followed by AMPK. Finally, (S)YS-51 improved glucose tolerance and insulin resistance in HFD mice. We concluded that (S)YS-51 attenuates NAFLD and insulin resistance in HFD mice by, at least, activation of SIRT1/AMPK signals. Thus, (S)YS-51 may be beneficial in NAFLD treatment.

  9. Insulin as a potential factor influencing blood pressure in amputees.

    Science.gov (United States)

    Rose, H G; Yalow, R S; Schweitzer, P; Schwartz, E

    1986-09-01

    War-injured, bilateral above-knee amputees are known to be at increased risk for cardiovascular mortality. To evaluate possible risk factors, we compared blood pressures and plasma glucose and insulin responses to orally administered glucose in 19 above-knee amputees from the Vietnam War (mean age, 36 +/- 1 years) with those of 12 age-matched unilateral below-elbow amputees. Body composition by densitometry and maximal oxygen consumption during arm or leg exercise were also determined. Nine of 19 leg amputees were hypertensive compared with one of 12 arm amputees. Their 3-hour average insulin responses were markedly increased (260 +/- 60 microU/ml) compared with those of normotensive leg (125 +/- 24 microU/ml) and arm amputees (101 +/- 20 microU/ml), and their mean body fat content (37.2%) also was elevated compared with that in both of these groups (23.2 and 22.6%, respectively). A unique finding was that both insulin response and body fat content were strongly and independently correlated with diastolic blood pressure (r = 0.55, p less than 0.01, and r = 0.62, p less than 0.01, respectively). We conclude that insulin may be a major factor in blood pressure regulation in the maturity-onset obesity that develops following traumatic leg amputation in young, healthy men.

  10. Textile wastewater purification through natural coagulants

    Science.gov (United States)

    Beltrán-Heredia, J.; Sánchez-Martín, J.; Rodríguez-Sánchez, M. T.

    2011-09-01

    A new coagulant obtained through polymerization of Acacia mearnsii de Wild tannin extract has been characterized in the removal of two dangerous dye pollutants: Alizarin Violet 3R and Palatine Fast Black WAN. This coagulant is lab-synthesized according to the etherification of tannins with glycidyltrimethylammonium chloride and formaldehyde and its performance in dye removal in terms of efficiency was high. Reasonably low coagulant dosages (ca. 50 mg L-1) reaches high capacity levels (around 0.8 for Alizarin Violet 3R and 1.6 for Palatine Fast Black WAN mg dye mg-1 of coagulant) and pH and temperature are not extremely affecting variables. The systems coagulant dyes were successfully modeled by applying the Langmuir hypothesis. q max and b parameters were obtained with an adjusted correlation factor ( r 2) above 0.8.

  11. Peripheral blood brain-derived neurotrophic factor in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, K; Vinberg, M; Kessing, L V

    2016-01-01

    Peripheral blood brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in bipolar disorder, speculated to mirror alterations in brain expression of BDNF. The research area is rapidly evolving; however, recent...... investigations have yielded conflicting results with substantial variation in outcomes, highlighting the need to critically assess the state of current evidence. The aims of the study were to investigate differences in peripheral blood BDNF concentrations between bipolar disorder patients and healthy control...... subjects and between affective states in bipolar disorder patients, including assessment of the effect of treatment of acute episodes on BDNF levels. A systematic review of English language studies without considering publication status was conducted in PubMed (January 1950-November 2014), Embase (1974...

  12. Sodium-glucose cotransporter-2 inhibitors and blood pressure decrease: a valuable effect of a novel antidiabetic class?

    Science.gov (United States)

    Imprialos, Konstantinos P; Sarafidis, Pantelis A; Karagiannis, Asterios I

    2015-11-01

    Diabetes mellitus is a major issue of public health, affecting more than 300 million people worldwide. Inhibitors of the sodium-glucose cotransporter-2 (SGLT-2) in the renal proximal tubule are a novel class of agents for the treatment of type 2 diabetes mellitus. Inhibition of the SGLT-2 results in reduced glucose reabsorption and improvement in glycemic control. Alongside glucose excretion, SGLT-2 inhibitors also have mild natriuretic and diuretic effects, combining actions of a proximal tubule diuretic and an osmotic diuretic; these properties are expected to lead to small blood pressure (BP) reductions. Clinical studies with dapagliflozin, canagliflozin, empagliflozin, ipragliflozin, luseogliflozin, and tofogliflozin used either as monotherapy or add-on therapy and compared with placebo or active treatment have also examined the effect of these agents on BP as a secondary endpoint. Although with some differences between individual agents, all of the approved SGLT-2 inhibitors provided a mild but meaningful reduction in office SBP and DBP. Recent studies with the use of ambulatory blood pressure monitoring suggest that the magnitude of this BP reduction can be even greater. The aim of this review is to systematically summarize and present the studies reporting the effect of approved SGLT-2 inhibitors on BP. PMID:26372321

  13. Cleavage of human high molecular weight kininogen markedly enhances its coagulant activity. Evidence that this molecule exists as a procofactor.

    OpenAIRE

    Scott, C F; Silver, L D; Schapira, M; Colman, R W

    1984-01-01

    High molecular weight kininogen (HMW)-kininogen, the cofactor of contact-activated blood coagulation, accelerates the activation of Factor XII, prekallikrein, and Factor XI on a negatively charged surface. Although prekallikrein and Factor XI circulate as a complex with HMW-kininogen, no physical association has been demonstrated between Factor XII and HMW-kininogen, nor has the order of adsorption to surfaces of these proteins been fully clarified. In this report we explore the requirements ...

  14. Synergistic Effects of Calcineurin Inhibitors and Steroids on Steroid Sensitivity of Peripheral Blood Mononuclear Cells.

    Science.gov (United States)

    Takeuchi, Hironori; Iwamoto, Hitoshi; Nakamura, Yuki; Hirano, Toshihiko; Konno, Osamu; Kihara, Yu; Chiba, Naokazu; Yokoyama, Takayoshi; Takano, Kiminori; Toraishi, Tatsunori; Okuyama, Kiyoshi; Ikeda, Chie; Tanaka, Sachiko; Onda, Kenji; Soga, Akiko; Kikuchi, Yukiko; Kawaguchi, Takashi; Kawachi, Shigeyuki; Unezaki, Sakae; Shimazu, Motohide

    2015-02-01

    The steroid receptor (SR) complex contains FKBP51 and FKBP52, which bind to tacrolimus (TAC) and cyclophilin 40, which, in turn, bind to cyclosporine (CYA); these influence the intranuclear mobility of steroid-SR complexes. Pharmacodynamic interactions are thought to exist between steroids and calcineurin inhibitors (CNIs) on the SR complex. We examined the effect of CNIs on steroid sensitivity. Methylprednisolone (MPSL) sensitivity was estimated as the concentration inhibiting mitosis in 50% (IC50) of peripheral blood mononuclear cells and as the area under the MPSL concentration-proliferation suppressive rate curves (CPS-AUC) in 30 healthy subjects. MPSL sensitivity was compared between the additive group (AG) as the MPSL sensitivity that was a result of addition of the proliferation suppressive rate of CNIs to that of MPSL and the mixed culture group (MCG) as MPSL sensitivity of mixed culture with both MPSL and CNIs in identical patients. IC50 values of MPSL and cortisol sensitivity were examined before and 2 months after CNI administration in 23 renal transplant recipients. IC50 and CPS-AUC values of MPSL were lower in the MCG than in the AG with administration of TAC and CYA. The CPS-AUC ratio of MCG and AG was lower in the TAC group. IC50 values of MPSL and cortisol tended to be lower after administration of TAC and CYA, and a significant difference was observed in the IC50 of cortisol after TAC administration. Steroid sensitivity increased with both TAC and CYA. Furthermore, TAC had a greater effect on increasing sensitivity. Thus, concomitant administration of CNIs and steroids can increase steroid sensitivity. PMID:26858893

  15. Interruption of the blood-stage cycle of the malaria parasite, Plasmodium chabaudi, by protein tyrosine kinase inhibitors

    Directory of Open Access Journals (Sweden)

    M.L. Gazarini

    2003-11-01

    Full Text Available Malaria is a devastating disease caused by a unicellular protozoan, Plasmodium, which affects 3.7 million people every year. Resistance of the parasite to classical treatments such as chloroquine requires the development of new drugs. To gain insight into the mechanisms that control Plasmodium cell cycle, we have examined the effects of kinase inhibitors on the blood-stage cycle of the rodent malaria parasite, Plasmodium chabaudi. In vitro incubation of red blood cells for 17 h at 37ºC with the inhibitors led to a decrease in the percent of infected cells, compared to control treatment, as follows: genistein (200 µM - 75%, staurosporine (1 µM - 58%, R03 (1 µM - 75%, and tyrphostins B44 (100 µM - 66% and B46 (100 µM - 68%. All these treatments were shown to retard or prevent maturation of the intraerythrocytic parasites. The diverse concentration ranges at which these inhibitors exert their effects give a clue as to the types of signals that initiate the transitions between the different developmental stages of the parasite. The present data support our hypothesis that the maturation of the intraerythrocytic cycle of malaria parasites requires phosphorylation. In this respect, we have recently reported a high Ca2+ microenvironment surrounding the parasite within red blood cells. Several kinase activities are modulated by Ca2+. The molecular identification of the targets of these kinases could provide new strategies against malaria.

  16. Legionella pneumophila Seropositivity-Associated Factors in Latvian Blood Donors

    Directory of Open Access Journals (Sweden)

    Olga Valciņa

    2015-12-01

    Full Text Available Continuous environmental exposure of humans to Legionella may induce immune responses and generation of antibodies. The aim of this study was to investigate the seroprevalence of Legionella pneumophila serogroups (SG 1–6 in the general healthy population and identify the associated host-related and environmental risk factors. L. pneumophila SG 1–6 seroprevalence among a total of 2007 blood samples collected from healthy donors was 4.8%. Seroprevalence was higher in women (5.9% than men (3.3% and in areas with a larger number of inhabitants, ranging from 3.5% in rural regions to 6.8% in the capital, Riga. Blood samples from inhabitants of apartment buildings tested positive for L. pneumophila in more cases (5.8% compared to those from inhabitants of single-family homes (2.7%. Residents of buildings with a municipal hot water supply system were more likely to be seropositive for L. pneumophila (OR = 3.16, 95% CI 1.26–7.91. Previous episodes of fever were additionally identified as a risk factor (OR = 2.42, 95% CI 1.43–4.1. In conclusion, centralized hot water supply, female gender and previous episodes of fever were determined as the main factors associated with L. pneumophila seropositivity in our study population.

  17. Legionella pneumophila Seropositivity-Associated Factors in Latvian Blood Donors

    Science.gov (United States)

    Valciņa, Olga; Pūle, Daina; Lucenko, Irina; Krastiņa, Dita; Šteingolde, Žanete; Krūmiņa, Angelika; Bērziņš, Aivars

    2015-01-01

    Continuous environmental exposure of humans to Legionella may induce immune responses and generation of antibodies. The aim of this study was to investigate the seroprevalence of Legionella pneumophila serogroups (SG) 1–6 in the general healthy population and identify the associated host-related and environmental risk factors. L. pneumophila SG 1–6 seroprevalence among a total of 2007 blood samples collected from healthy donors was 4.8%. Seroprevalence was higher in women (5.9%) than men (3.3%) and in areas with a larger number of inhabitants, ranging from 3.5% in rural regions to 6.8% in the capital, Riga. Blood samples from inhabitants of apartment buildings tested positive for L. pneumophila in more cases (5.8%) compared to those from inhabitants of single-family homes (2.7%). Residents of buildings with a municipal hot water supply system were more likely to be seropositive for L. pneumophila (OR = 3.16, 95% CI 1.26–7.91). Previous episodes of fever were additionally identified as a risk factor (OR = 2.42, 95% CI 1.43–4.1). In conclusion, centralized hot water supply, female gender and previous episodes of fever were determined as the main factors associated with L. pneumophila seropositivity in our study population. PMID:26703696

  18. 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.

  19. Legionella pneumophila Seropositivity-Associated Factors in Latvian Blood Donors

    OpenAIRE

    Olga Valciņa; Daina Pūle; Irina Lucenko; Dita Krastiņa; Žanete Šteingolde; Angelika Krūmiņa; Aivars Bērziņš

    2015-01-01

    Continuous environmental exposure of humans to Legionella may induce immune responses and generation of antibodies. The aim of this study was to investigate the seroprevalence of Legionella pneumophila serogroups (SG) 1–6 in the general healthy population and identify the associated host-related and environmental risk factors. L. pneumophila SG 1–6 seroprevalence among a total of 2007 blood samples collected from healthy donors was 4.8%. Seroprevalence was higher in women (5.9%) than men (3.3...

  20. Efficacy of recombinant factor VIIa administered by continuous infusion to haemophilia patients with inhibitors

    NARCIS (Netherlands)

    Mauser-Bunschoten, EP; Koopman, MMW; Goede-Bolder, ADE; Leebeek, FWG; Van der Meer, J; Kooij, GMV; Van der Linden, PWG

    2002-01-01

    We have prospectively monitored treatment of haemophilia patients with inhibitors by recombinant factor VIIa (rFVIIa) administered by continuous infusion to obtain more insight in the underlying factors of the clinical efficacy of this administration method. At present, 43 treatment episodes of 14 d

  1. 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...... 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...... be used to monitor the course of these common and potentially life-threatening infections....

  2. Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers.

    Science.gov (United States)

    Ayatollahi, Hossein; Javan, Atefeh Ordoei; Khajedaluee, Mohammad; Shahroodian, Masood; Hosseinzadeh, Hossein

    2014-04-01

    Saffron showed some effects on blood coagulation and platelet aggregation in in vitro and in vivo studies. In a clinical trial with a limited number volunteers, saffron tablets influenced on bleeding time. In this study, the effect of saffron on plasma level of fibrinogen, factor VII (as coagulant agent), C and S protein (as anti-coagulant agent), PT and PTT in a larger sample size was evaluated. The study was a double-blind, placebo-controlled study consisting of 1 week treatment with 200 mg and 400 mg saffron tablets. Sixty healthy volunteers (age range 20-50 years) were selected for the study. The volunteers were divided into three groups of 20 each. Group 1 received placebo; Groups 2 and 3 received 200 mg and 400 mg saffron tablets, respectively, for 7 days (1 tablet per day). Before and after 7 days treatment and also 1 month after that, blood samples were taken. The plasma levels of fibrinogen, factor VII, C and S protein, PT and PTT were evaluated. Statistical analysis showed no difference between groups for any of evaluated factors. This study rejected any effect of saffron with dose of 200 and 400 mg for 1 week on coagulant and anticoagulant system.

  3. Treatment of Disseminated Intravascular Coagulation.

    Science.gov (United States)

    Makruasi, Nisa

    2015-11-01

    Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic activation of blood coagulation, generation of thrombin, and leading to disturbance of the microvasculature. In this article, definition and diagnostic criteria of DIC depend on the International Society of Thrombosis and Haemostasis (ISTH). There is no gold standard for diagnosis of DIC, only low quality evidence is used in general practice. Many diagnostic tests and repeated measurement are required. For the treatment of DIC, there is no good quality evidence. The most important treatment for DIC is the specific treatment of the conditions associated DIC. Platelets and/or plasma transfusion may be also necessary if indicated. Nevertheless, there is no gold standard for diagnosis and treatment of DIC, we use only low quality evidence in general practice.

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

    OpenAIRE

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

    2016-01-01

    Introduction 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. M...

  5. 不同孕期妊娠妇女凝血四项指标变化及意义%Analysis of the blood coagulation test of pregnant women in different stage and discuss its clinical significance

    Institute of Scientific and Technical Information of China (English)

    魏文迅; 林进考

    2008-01-01

    Objective To study the results of blood coagulation test,including PT,APTT,FG and TT of pregnant women in different stage,and to discuss its clinical significance.Methods Blood coagulation monitor(STA-GO-ArT4,French)was used in this study.The experiment samples were divided into four grroups:group intermediate stage gestation(30 persons),group advanced stage gestation(26 persons),group in labor(30 persons)and group normal of none-gestation(37 persons).The prothrombin time(PT),activated partiat thromboplastin time(APTT).fibrinogen(FG)and thrombin time(TT)of these persons were detected.At last,the data of the test was analysised.Results The PT,FG and TT of the group advanced stage gestation and group in labor were higher compared with the group normal of none-gestation(P<0.05).Conclusion The blood coagulation function of pregnant women in different stage is different from the none-pregnant women,and it is important to know the PT,APTT,FG and TT promptly.%目的 探讨妊娠妇女不同孕期凝血酶原时间(PT)、部分凝血活酶时间(APTT)、纤维蛋白原(FG)和凝血酶时间(TT)四项反映凝血功能指标的变化及其临床意义.方法 采用法国STAGO-ArT4血凝仪检测86例正常中孕、晚孕、临产妇女和37例正常非孕妇女的PT、APTT、FG和TT,并对检测结果进行比较.结果:晚孕组和临产组与健康对照组比较,PT、FG和TT差异有统计学意义(P<0.05).结论 不同孕期妊娠妇女凝血功能发生改变,及时了解这些变化具有重要临床意义.

  6. 重组凝血因子Ⅶ表达和合成机制的研究进展%Research advances of recombinant coagulation factor VII expression and synthesizing mechanism

    Institute of Scientific and Technical Information of China (English)

    彭林; 于笑; 蔡燕飞; 金坚; 李华钟

    2015-01-01

    Haemophilia is caused by lack of coagulation factor VIII or IX in patients′blood with inadequate hemostasis.Currently recombinant coagulation factor VII(rFVII)produced in different cells is used against clini-cal bleeding of haemophilia patients.To enhance the production and activity of rFVII;some eukaryotic cells such as baby hamster kidney(BHK);Chinese hamster ovary(CHO);insect cell and fish embryo;were used to express rFVII.Meanwhile;the effect of functional gene on the activity of rFVII and the limitation of rFVII production caused by post-translational modification were investigated by different methods.The role of rFVII in hemostasis;synthesis of rFVII in different eukaryotic cells and impact on production of post-translational modification are reviewed in this article.%血友病是由于人体内缺乏相应凝血因子造成的凝血障碍,目前主要利用基因重组技术在不同细胞中表达重组凝血因子Ⅶ(Ⅶ因子)从而对血友患者出血进行治疗。为有效提高重组Ⅶ因子的产量及活性,已有研究者尝试利用不同真核表达系统合成重组Ⅶ因子,如BHK细胞、CHO细胞、昆虫细胞和鱼胚胎等。同时,不同外源功能性基因对重组Ⅶ因子活性和翻译后修饰对表达产量的影响也通过不同方法进行探究。本文从Ⅶ因子在凝血途径中的作用、重组表达重组Ⅶ因子和翻译后修饰对合成的影响3个方面对重组Ⅶ因子表达和合成机制研究进行了综述。

  7. Blood Lipids and other Related Risk Factors of stroke

    Institute of Scientific and Technical Information of China (English)

    Liu YAND; Hiu Lu

    2000-01-01

    Abstract To assess the ralationship between incidence of stroke and blood lipids, apolipoprolcin (apo) , 219 patients with stroke(cerebral hemorrhage 87, cerebral infarction 132) , diagnosed with the aid of CT, were examined. The levels of serum total cholesterol, triglycerioes, apo-A, apo-B were calculatea. 160 cases with no disorder in metabolism of blood lipids or other disease of meurologic system were taken as centrol group. The results zhowed that the ratio of high density lipoprotein cholesterol and low clensity lipoprotein cholesterol was iower than.that of control group(p<0. 05) . In the patients group, cases with diabetes, hypentension coronary heart disease or onesity, the levels of blood liprds. triglyceride and cholesterol were higher than those vithout above mentioned disease The condusion is, that there is certain reletionship between the contents of bliid lipids. lipoprotein and it sulqraction HDL2, HDL3 and cerebrovasculor cisease. The radis of high density lipoprotein and low density lipoprolein is the important factor in predicting of stroke

  8. A Study of the Relation between Systemic Blood Coagulation and Leukopenia in Local Irradiation%放疗局部照射中全身凝血功能与白细胞减少的关系

    Institute of Scientific and Technical Information of China (English)

    耿冲; 张旭光; 郭峰; 叶涛; 刘亚洲; 沈文彬; 顾峰

    2013-01-01

    目的 观察放疗局部照射下全身凝血功能的变化,并探讨华法令干预缓解白细胞减少的效果.方法 新西兰白兔分为阴性对照组、单纯照射组、照射+抗凝组.照射前、照射后24 h检测凝血酶原时间、PT国际标准化比值、外周血白细胞计数.单纯照射组仅接受一次全胸部照射,总剂量20 Gy.照射+抗凝组照射前喂服抗凝血药华法令.照射后24 h处死动物,采取左胸第十肋骨骨髓代表照射靶区内骨髓,第三腰椎左侧横突骨髓代表靶区外骨髓,行骨髓像观察.结果 单纯照射组照射前后凝血功能无明显变化,白细胞明显减少.照射+抗凝组照射前后凝血功能均被阻断,白细胞明显减少.2组动物照射靶区内骨髓有核细胞明显减少,靶区外骨髓有核细胞计数正常.结论 造成白细胞减少的局部照射剂量不能够改变全身的凝血状态;完全阻断凝血所消耗的白细胞减少也不能阻断局部照射造成的白细胞减少.%Objective To observe systemic blood coagulation changes in local irradiation, and to study the influence of warfarin on leukocypenia. Methods New Zealand white rabbits were divided into negative control group, radiation group, irradiation + anticoagulant group. Before irradiation and 24 hours after irradiation, prothrombin time, PT international normalized ratio and WBC count were detected. The radiation group only accepted a full chest irradiation of 20 Gy. In the irradiation + anticoagulant group,rabbits was fed with the anti-clotting drug warfarin before irradiation. The animals were sacrificed in 24 hours after irradiation, bone marrow of the tenth rib of left chest represented irradiation target region bone marrow, and the third lumbar transverse process bone marrow represented target line bone marrow, and the bone marrow was examined. Results Coagulation function before and after the irradiation of the radiation group had no significant change, white blood cells was

  9. Effects of Al-coagulant sludge characteristics on the efficiency of coagulants recovery by acidification.

    Science.gov (United States)

    Chen, Yi-Jui; Wang, Wen-May; Wei, Ming-Jun; Chen, Jiann-Long; He, Ju-Liang; Chiang, Kung-Yuh; Wu, Chih-Chao

    2012-12-01

    This study evaluated the effects of Al-coagulant sludge characteristics on the efficiency ofcoagulant recovery by acidification with H2SO4. Two sludge characteristics were studied: types of coagulant and textures of the suspended solid in raw water. The coagulant types are aluminium sulphate and polyaluminium chloride (PACl); the textures of the suspended solid are sand-based and clay-based. Efficiency of aluminium recovery at a pH of 2 was compared for different sludges obtained from water treatment plants in Taiwan. The results showed that efficiency of aluminium recovery from sludge containing clayey particles was higher than that from sludge containing sandy particles. As for the effect of coagulant types, the aluminium recovery efficiency for sludge using PACl ranged between 77% and 100%, whereas it ranged between 65% and 72% for sludge using aluminium sulphate as the coagulant. This means using PACl as the coagulant could result in higher recovery efficiency of coagulant and be beneficial for water treatment plants where renewable materials and waste reduction as the factors for making decisions regarding plant operations. However, other metals, such as manganese, could be released with aluminium during the acidification process and limit the use of the recovered coagulants. It is suggested that the recovered coagulants be used in wastewater treatment processes. PMID:23437650

  10. The saliva proteome of the blood-feeding insect Triatoma infestans is rich in platelet-aggregation inhibitors

    Science.gov (United States)

    Charneau, Sébastien; Junqueira, Magno; Costa, Camila M.; Pires, Daniele L.; Fernandes, Ellen S.; Bussacos, Ana C.; Sousa, Marcelo V.; Ricart, Carlos André O.; Shevchenko, Andrej; Teixeira, Antonio R. L.

    2007-12-01

    The saliva of the bloodsucking bug Triatoma infestans vector of Chagas disease contains an anti-hemostatic molecular cocktail that prevents coagulation, vasoconstriction and platelet aggregation in a vertebrate prey. In order to characterize T. infestans saliva proteome, we separated the secreted saliva by two-dimensional gel electrophoresis (2-DE). More than 200 salivary proteins were detected on the 2-DE map, mainly in the alkaline region. By nanoLC-MS/MS analysis using a LTQ-Orbitrap equipment followed by a combination of conventional and sequence-similarity searches, we identified 58 main protein spots. Most of such proteins possess potential blood-feeding associated functions, particularly anti-platelet aggregation proteins belonging to lipocalin and apyrase families. The saliva protein composition indicates a highly specific molecular mechanism of early response to platelet aggregation. This first proteome analysis of the T. infestans secreted saliva provides a basis for a better understanding of this fluid protein composition highly directed to counterpart hemostasis of the prey, thus promoting the bug's blood-feeding.

  11. Inhibition of amikacin on platelet aggregation and blood coagulation%丁胺卡那霉素对血小板聚集和凝血功能的抑制作用

    Institute of Scientific and Technical Information of China (English)

    费鲜明; 周永列; 邱莲女; 吴建国; 张可

    2010-01-01

    platelet aggregation ( r = 0.939, P <0.05) was observed, as well as APTT (r >0.870, P<0.05).At 30 mg/L, 91 mg/L, and 910 mg/L of amikacin groups, the P-selectin and Fg-R expression were remarkably inhibited with a dose-dependent manner, the CT was notably enhanced [Fwithin subjects =21.44, 26.24, ( >29.81 ), P <0.01].At 0 mg/L,30 mg/L, 91 mg/L and 910 mg/L of amikacin groups, the PT values were ( 14.7 ± 1.9) s, ( 15.2 ± 1.7) s,(15.6±1.5) s and (22.1 ±2.1) s, respectively (F=8.21,P<0.05), but there was no markeddifference for the levels of GP Ⅱ b/Ⅲ a, TT, Fg and plasma Ca2+ among the four groups ( P > 0.05 ).After 30 minutes of amikacin treatment, the maximial ratio of platelet aggregation (51.6 ± 10.1)%, the expression levels of P-selectin (6.8 ± 1.8) % and Fg-R ( 20.1 ± 5.8 ) % were significantly lower than those [(66.8 ± 11.4)%, ( 10.9 ±3.1 )% and (28.5 ±7.4)%] before amikacin treatment, but APTT (49.8 ±5.9) s and CT (660 ±59) s were remarkably higher than those [(26.9 ±3.8) s and (410 ±45) s] before amikacin treatment, respectively ( t = 5.456,8.875,7.423,10.012,11.322, P < 0.01 ), while the GP Ⅱ b/Ⅲ a expression, PT and Ca2+ concentration had no significant changes ( P > 0.05).Conclusions There are inhibitory effects of amikacin on platelet aggregation mainly through the inhibition of both fibrinogen receptor activation and secretion reaction of activated platelet. Amikacin may also inhibit pathway of coagulation system factor to prevent blood coagulation.Therefore, risk of hemorrhage may be investigated in the patients with amikacin for anti-infection treatment.%目的 观察丁胺卡那霉素对血小板聚集和凝血功能试验的抑制作用,探讨其对止血功能的影响及相关作用机制.方法 将不同浓度丁胺卡那霉素分别与献血者富血小板血浆和乏血小板血浆作用,分为4组:0 mg/L组、30 mg/L组、91 mg/L组和910 mg/L组.以血小板聚集分析仪检测ADP诱导的血小板最大聚集

  12. Does human semen contain a functional haemostatic system? A possible role for Tissue Factor Pathway Inhibitor in fertility through semen liquefaction.

    Science.gov (United States)

    Lwaleed, Bashir A; Greenfield, Robert S; Birch, Brian R; Cooper, Alan J

    2005-05-01

    There is already evidence that a few components of the haemostatic system exist in semen. If these comprise a functional system, they may have a role in seminal clotting and liquefaction processes and ultimately may influence fertility. What might be expected in semen as collected from fertility clinics i.e., after having both coagulated and subsequently liquefied is uncertain. It does however still contain significant amounts of Tissue Factor (TF) although its effect on semen quality remains poorly understood. The present study analyses semen for Tissue Factor Pathway Inhibitor (TFPI). Measurements were made in seminal plasma, swim-up sperm and prostasomes and its relationship with conventional fertility parameters assessed. TFPI antigen levels in seminal plasma were measured in a total of 176 subjects using an Enzyme-linked immunosorbent assay (ELISA). These include sub-fertile (n=37), normally fertile (n=40), fertile sperm donor (n=34), vasectomized subjects (n=65) and in a further group defined by normality in several parameters derived from the World Health Organization (WHO) fertility criteria and termed "pooled normal semen parameters" (PNSP). For characterization studies, both TFPI activity and antigen were measured on whole semen, swim-up sperm and prostasome-rich fraction (n=5). TFPI levels were significantly higher in normal men as compared to sub-fertile (Psemen and the PNSP group. TFPI levels also correlated with semen liquefaction time, normal semen viscosity, sperm progression, percentage of motile sperm and sperm counts (density). In conclusion, the present finding substantiates the concept of an active clotting system in human semen. TFPI could regulate the activity of abundant TF, as it does elsewhere. Given a functional set of coagulation factors in semen, the TF/TFPI balance might impinge on its liquefaction and hence on global fertility. PMID:15886798

  13. Delirium in the geriatric unit: proton-pump inhibitors and other risk factors

    Directory of Open Access Journals (Sweden)

    Otremba I

    2016-04-01

    Full Text Available Iwona Otremba, Krzysztof Wilczyński, Jan SzewieczekDepartment of Geriatrics, School of Health Sciences in Katowice, Medical University of Silesia, Katowice, PolandBackground: 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.Objective: Evaluate specific factors for development of delirium in a geriatric ward setting.Methods: 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.Results: 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; P<0.001, previous delirium incidents (OR =2.23; CI =1.47–3.38; P<0.001, previous fall 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.Conclusion: 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.Keywords: delirium

  14. 2型糖尿病患者凝血状态研究%The study of blood coagulation status in type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    穆志静; 王立

    2013-01-01

    目的 探讨2型糖尿病患者合并血管病变对凝血状态的影响.方法 纳入2型糖尿病住院患者311例,依据有无大血管并发症分为3组,即单纯糖尿病组130例,糖尿病合并高血压组151例,糖尿病合并冠心病组30例,同时选择我院同期健康体检者30例作为健康对照组.检测抗凝血酶-III(AT-III)、蛋白C(PC)、蛋白S(PS)、活化部分凝血活酶时间(APTT)、血浆凝血酶原时间(PT)、血浆纤维蛋白原(Fib)、血浆凝血酶时间(TT))水平评价凝血功能.结果 与健康对照组相比较,糖尿病组AT-III、PC、PS活性明显降低,凝血四项中APTT、PT降低、Fib升高,2组比较差异有统计学意义(P<0.05).糖尿病合并冠心病组与单纯糖尿病组相比,PC、PS差异有统计学意义(P<0.05).糖尿病合并冠心病组Fib及PLT升高较单纯糖尿病组更为明显,差异有统计学意义(P<0.05).结论 糖尿病患者抗凝血功能紊乱,处于血栓前状态,合并心血管并发症患者尤为明显.AT-III、PC、PS及凝血四项的测定可能有利于糖尿病患者凝血状态的评估,有利于血管并发症的早期干预.%Objective To explore the changes and clinical significance in coagulation anti-coagulation and fibrinolysis system in patients with type 2 diabetes mellitus ( DM ). Methods To measure thrombin time ( TT ), activated partial thrombo-plastin time ( APTT ), prothrombin time ( PT ), and fibrinogen ( Fib ), anti-thrombin Ⅲ ( AT-Ⅲ ), protein C ( PC ), protein S ( PS ) in 311 patients with type 2 diabetes mellitus from 2010 to 2011. These patients were categorized as single DM group, DM with hypertension group, DM with coronary heart disease group. At the same time, 30 health)' people were selected as contrast group. SPSS software was used for statistic analysis. Results The activity of AT-Ⅲ,PC,PS of type 2 diabetes melli-tus were progressively lower than those of control group. There was a significant difference between single DM

  15. 组织因子途径抑制因子对生物材料表面血小板粘附的影响%Effect of Tissue Factor Pathway Inhibitor on the Adhesion of Platelet onto Polyethylene and Polyvinylchloride Membranes

    Institute of Scientific and Technical Information of China (English)

    冷希岗; 王传华; 宋丽萍; 王彭延

    2001-01-01

    Tissue factor pathway inhibitor(TFPI) is the majo rinhibitor of the extrinsic pathway of the blood coagulation cascade. Our previous study showed that TFPI could obviously prolong the blood coagulation time on the surface of polyethelene(PE) and polyvinylchloride(PVC) membranes in vitro and decrease the generation of thrombus on Dacron membrane in vivo. In the pressent sutdy, the effect of TFPI on the adhesion of platelet onto PE and PVC membr anes was investigated. PE or PVC membrane was cut into small pieces and incubated in 96-well culture plate with GST or GST-TFPI fusion protein at 4℃ over night. Freshly collected rabbit blood was mixed with 3.8% sodium citrate. Platelet-rich plasma was separated by centrifugation and then incubated with the treated membranes at 37℃ for 30 minutes. The membranes were then washed, fixed, and freeze-dehydrated Adhesion of platelet was observed through scanning electronic microscope. The result showed that GST-TFPI treatment significantly decrea sed the number of platelet adhered on the membrane when compared with the GST and control group,and it suggested that TFPI might have a great potential to be used as an anticoagulant for improving the hemocompatibility of biomaterials.%组织因子途径抑制因子(tissue factor pathway in hibitor, TFPI)是组织因子凝血途径的主要抑制因子,具有抑制组织因子、凝血因子VIIa、 和Xa的功能。我们以前的研究显示TFPI在体外可以明显延长被修饰材料表面的凝血时间,在 体内显著减少材料表面的血栓形成。本文观察了TFPI包被对聚乙烯和聚氯乙烯材料表面血小 板粘附的影响。结果显示,通过TFPI处理后,上述两种材料表面的血小板粘附数目较对照组 明显减少,提示TFPI可通过抑制血小板在材料表面的粘附起到改善生物材料血液相容性的作用。

  16. Update and critical appraisal of combined timolol and carbonic anhydrase inhibitors and the effect on ocular blood flow in glaucoma patients

    Directory of Open Access Journals (Sweden)

    Adam M Moss

    2010-03-01

    Full Text Available Adam M Moss, Alon Harris, Brent Siesky, Deepam Rusia, Kathleen M Williamson, Yochai ShoshaniDepartment of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USAAbstract: Topical hypotensive therapy with both timolol and carbonic anhydrase inhibitors has been shown to be efficacious at reducing intraocular pressure. Many prospective studies have also suggested that carbonic anhydrase inhibitors augment ocular blood flow and vascular regulation independent of their hypotensive effects. Although consistent in their findings, these studies must be cautiously interpreted due to the limitations of study design and specific blood flow imaging modalities. The purpose of this review is to appraise and critically evaluate the current body of literature investigating the effects of combined treatment with topical carbonic anhydrase inhibitors and timolol in patients with glaucoma with respect to ocular blood flow, visual function, and optic nerve head structure.Keywords: ocular blood flow, carbonic anhydrase inhibitor, timolol, glaucoma, visual function, optic nerve head

  17. Egress of CD19+CD5+ cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients

    OpenAIRE

    Chang, Betty Y.; Francesco, Michelle; de Rooij, Martin F.M.; Magadala, Padmaja; Steggerda, Susanne M.; Huang, Min Mei; Kuil, Annemieke; Herman, Sarah E. M.; Chang, Stella; Pals, Steven T; Wilson, Wyndham; Wiestner, Adrian; Spaargaren, Marcel; Buggy, Joseph J; Elias, Laurence

    2013-01-01

    MCL cells are mobilized into the peripheral blood of patients treated with the BTK inhibitor ibrutinib.Ibrutinib dose-dependently inhibits BCR- and chemokine-mediated adhesion and migration of MCL cells.

  18. Changes of coagulation function and factor analysis for patients taking hemodialysis%血液透析患者凝血功能变化及因素分析

    Institute of Scientific and Technical Information of China (English)

    连芬; 陈哿菲; 赵冬梅; 俞燕

    2015-01-01

    目的:探讨血液透析治疗对患者凝血功能的影响及原因分析。方法选取我院2012年1月~2014年4月共68例进行维持性血液透析患者透析前后的血液样本,采用流式细胞术检测血小板表面P-选择素。用间接酶链免疫吸附试验检测超敏C反应蛋白、内皮血管性血友病因子和D-二聚体。并通过对患者的观察、病例资料的整理以及对血透后透析器血容量测量等,回顾性分析血液透析患者发生凝血功能变化的原因及分析。结果经治疗后患者均痊愈出院,治疗后PT和FIB值明显少于治疗前(P0.05)。D-二聚体治疗前阳性率50%,治疗后为0,差异有统计学意义(P0.05). Positive rate of D-dimer was 50%before the treatment and 0.0% after the treatment, and the difference compared before and after the treatment was statistically significant (P<0.05). Results of P-selectin on platelet surface, ultra-sensitive C-reactive protein, endothelial von Wille-brand factor and D-dimer after hemodialysis were significantly higher than those before hemodialysis, and the differ-ences were statistically significant. Factors affecting changes of patients' coagulation function included individual health quality, doctors' inaccurate assessment, inappropriate anti-coagulation, insufficient usage of heparin and inappropriate operation techniques by nurses. Conclusion Medical staff should enhance their knowledge of anti-coagulation, improve the assessment and testing of coagulation status for patients taking hemodialysis, provide anti-coagulation protocol timely and properly, and practice operation techniques. Meanwhile, although heparin is used during treatment, patients may still be highly coagulated. Therefore, regular monitoring of coagulation indicators is able to effectively reduce co-agulation during hemodialysis.

  19. Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Ankylosing Spondylitis.

    Directory of Open Access Journals (Sweden)

    Inês P Perpétuo

    Full Text Available Ankylosing Spondylitis (AS is characterized by excessive local bone formation and concomitant systemic bone loss. Tumor necrosis factor (TNF plays a central role in the inflammation of axial skeleton and enthesis of AS patients. Despite reduction of inflammation and systemic bone loss, AS patients treated with TNF inhibitors (TNFi have ongoing local bone formation. The aim of this study was to assess the effect of TNFi in the differentiation and activity of osteoclasts (OC in AS patients.13 AS patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. 25 healthy donors were recruited as controls. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and qRT-PCR for OC specific genes were performed.RANKL+ circulating lymphocytes (B and T cells and IL-17A, IL-23 and TGF-β levels were decreased after TNFi treatment. We found no differences in the frequency of the different monocyte subpopulations, however, we found decreased expression of CCR2 and increased expression of CD62L after TNFi treatment. OC number was reduced in patients at baseline when compared to controls. OC specific gene expression was reduced in circulating OC precursors after TNFi treatment. However, when cultured in OC differentiating conditions, OC precursors from AS TNFi-treated patients showed increased activity as compared to baseline.In AS patients, TNFi treatment reduces systemic pro osteoclastogenic stimuli. However, OC precursors from AS patients exposed to TNFi therapy have increased in vitro activity in response to osteoclastogenic stimuli.

  20. The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow or blood velocity, but nevertheless induces headache in healthy subjects

    DEFF Research Database (Denmark)

    Kruuse, Christina; Thomsen, Lars Lykke; Jacobsen, Torsten Bjørn;

    2002-01-01

    Cyclic nucleotides are important hemodynamic regulators in many tissues. Glyceryl trinitrate markedly dilates large cerebral arteries and increases cGMP. Here, the authors study the effect of sildenafil, a selective inhibitor of cGMP-hydrolyzing phosphodiesterase 5 on cerebral hemodynamics...... and headache induction. Ten healthy subjects were included in a double-blind, placebo-controlled crossover study where placebo or sildenafil 100 mg (highest therapeutic dose) were administered on two separate days. Blood velocity in the middle cerebral artery (Vmca) was recorded by transcranial Doppler...

  1. Coagulant and anticoagulant activities of Bothrops lanceolatus (Fer de lance) venom.

    Science.gov (United States)

    Lôbo de Araújo, A; Kamiguti, A; Bon, C

    2001-01-01

    Bothrops lanceolatus venom contains caseinolytic, phospholipase, esterase and haemorrhagic activities. We have investigated the coagulant and anticoagulant actions of B. lanceolatus venom on human citrated plasma and on purified plasma components. Although B. lanceolatus venom up to 50 microg/ml was unable to clot citrated plasma, at concentrations > or = 5 microg/ml the venom dose-dependently clotted purified human fibrinogen, indicating the presence of a thrombin-like enzyme. Human plasma (final concentration > or = 12.5%) dose-dependently inhibited the venom-induced fibrinogen clotting. This finding suggested that endogenous plasma protease inhibitors can affect the venom's action on fibrinogen. To investigate this possibility, B. lanceolatus venom was incubated with different plasma protease inhibitors and the activity on fibrinogen tested. alpha(2)-Macroglobulin and alpha(1)-antitrypsin did not interfere with the coagulant activity of the venom whereas the antithrombin-III/heparin complex partially inhibited this activity. A non-toxic, acidic phospholipase A(2) purified from B. lanceolatus venom prolonged the activated partial thromboplastin time in human plasma from 39.7+/-0.5 s (control with saline) to 60.2+/-0.9 s with 50 microg of PLA(2) (p<0.001), suggesting an anticoagulant activity associated with this enzyme. This anticoagulant activity may account for some of the effects of the venom on blood coagulation. PMID:10978756

  2. Polymorphisms of the coagulation factor Ⅶ gene and its plasma levels in relation to acute cerebral infarction differences in allelic frequencies between Chinese Han and European populations

    Institute of Scientific and Technical Information of China (English)

    康文英; 王鸿利; 熊立凡; 王学锋; 储海燕; 璩斌; 刘湘帆; 尹俊; 段宝华; 王振义

    2004-01-01

    Background Coagulation factor Ⅶ (F Ⅶ) levels in plasma are usually related to ischemic heart disease (IHD) and cerebral infarction shares many of the risk factors related to IHD. Is there any relationship between factor Ⅶ and cerebral infarction? We investigated the relationship between F Ⅶ and acute cerebral infarction and reported genotype frequencies and allelic frequencies of FⅦ gene polymorphisms in the Chinese Han population.Methods We recruited 62 patients with acute cerebral infarction confirmed by magnetic resonance imaging (MRI) from Ruijin Hospital, and 149 age-matched patients clinically free of vascular disease to act as controls. All of them were unrelated, and were from the Chinese Han population. FⅦ coagulant activity (FⅦc) was determined using an clotting assay, activated FⅦ (FⅦa) and FⅦ Ag were assayed using enzyme immunoassay kits. The FⅦ gene polymorphisms to be detected included-401G/T, -402G/A, 5'F7A1/A2, IVS7 and R353Q. 5'F7 and IVS7 were revealed by means of a PCR and direct agarose gel electrophoresis. The rest were examined by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The results showed that FⅦc, FⅦAg and FⅦa were higher in the acute cerebral infarction group than in the control group (P<0.01, P<0.05, P<0.05, respectively). There were no significant differences in the genotype frequencies of FⅦ gene polymorphisms between the two groups. The allelic frequencies in the Chinese Han population were as follows: -401G/T (96.64/3.36), -402G/A (52.01/47.99), 5'F7A1/A2(96.64/3.36), IVS7 H5/H6/H7/H8 (0.34/52.35/46.98/0.34) and R353Q (95.64/4.36). There were significant differences (P<0.01, P<0.001, P<0.001, P<0.001, P<0.001, respectively) in these allelic frequencies between the Chinese Han and European populations.Conclusions The results indicate that increased plasma FⅦ levels may contribute to thrombosis in cerebral infarction. And there was no significant difference

  3. 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.

  4. Rationale for clinical trials of coagulation: reactive drugs in hepatocellular carcinoma.

    Science.gov (United States)

    Zacharski, Leo R; Hommann, Merten; Kaufmann, Roland

    2004-09-01

    Evidence for the regulation of cancer growth by components of the blood coagulation mechanism provides abundant opportunity for the development of novel hypotheses for the experimental treatment of malignancy. Information available on the heterogeneity in mechanisms of interaction between various cancer cell types, and procoagulant and fibrinolytic pathways, platelets, glycosaminoglycan-regulated growth factors and cell-adhesion molecules indicates that insightful clinical trial design may allow targeting of individual cancer cell types with agents capable of intercepting mechanisms of growth control that are relevant to specific tumor types. This paper reviews the evidence that the common anticoagulant, heparin, inhibits hepatocellular carcinoma cell proliferation and hepatocellular carcinoma tumor dissemination in experimental animals. Clinical trials of heparin performed to date have shown increased tumor response rates and survival in other tumor types. Expression of urokinase-type plasminogen activator by hepatocellular carcinoma cells enhances tumor cell proliferation, motility, invasiveness and metastatic dissemination. Inhibition of the urokinase-type plasminogen activator/plasmin system by protease inhibitors such as aprotinin (Trasylol, Bayer) have shown improvement in the clinical course of certain tumor types. These data suggest that drugs that are well-known in the field of vascular medicine may find a role in the treatment of hepatocellular carcinoma, a common tumor type that has resisted containment by other means. PMID:15350179

  5. Changes of balance between proteinase and their inhibitors in blood of pigs with high-velocity missile wounds

    Institute of Scientific and Technical Information of China (English)

    周元国; 朱佩芳; 周继红; 李晓炎

    2003-01-01

    Objective: To study the effect of imbalance between lysosomal enzymes and their inhibitors in blood on disturbance of the local and whole body after trauma. Methods: The dynamic changes of lysosomal enzymes and proteinase inhibitors were studied in 12 pigs with femoral comminuted fractures in both hind limbs caused by high velocity missiles. Four normal pigs served as controls. Results: After injury, the activity of Cathepsin D in arterial plasma increased gradually and reached the highest level at 8 hours, acid phosphatase in serum began to increase at 12 hours and the value of serum elastase did not change significantly. The level of α1-antitrypsin, a proteinase inhibitor in plasma, decreased significantly in the early stage after injury [73.5%±6.4% and 81.0%±5.1% of the baseline value (1.67 μmol*ml-1*min-1± 0.29 μmol*ml-1*min-1) at l and 2 hours after injury, respectively, P<0.05], then increased gradually and was higher than the baseline value at 12 hours after injury. Conclusions: Imbalance between lysosomal enzymes and proteinase inhibitors occurs soon after injury, which might result in continuous tissue damage and play an important role in the disturbance of general reaction after injury.

  6. Investigation on change regulation of blood coagulation function before and after treatment of snake bite patients%凝血功能在毒蛇咬伤治疗前后变化规律的研究

    Institute of Scientific and Technical Information of China (English)

    梁剑宁; 唐荣德; 张跃; 陈森雄; 张冠新; 郭伟文; 曾燕玲

    2015-01-01

    目的:探讨各种毒蛇咬伤患者治疗前后凝血功能的变化规律。方法选择近2年住院治疗、属于何种蛇伤诊断明确的毒蛇咬伤患者226例为研究对象,其中银环蛇咬伤39例,竹叶青蛇咬伤76例,眼镜蛇咬伤47例,眼镜王蛇咬伤24例,蝰蛇咬伤40例。这些患者在治疗前后各时段均进行5项凝血指标检测,按蛇种、时段及病情对检测结果进行统计分析。结果银环蛇咬伤轻症患者与重症患者比较,仅治疗前重症患者D二聚体(D‐D)水平明显高于轻症患者,差异有统计学意义(P<0.05);竹叶青蛇咬伤重症患者治疗前血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、和D‐D水平升高、纤维蛋白原(Fib)水平降低,Fib和D‐D水平在治疗前后与轻症差异有统计学意义(P<0.05);眼镜蛇和眼镜王蛇咬伤患者各项指标在治疗前后差异无统计学意义(P>0.05),仅眼镜蛇咬伤重症患者D‐D水平在治疗前与轻症比较差异有统计学意义(P<0.05);蝰蛇咬伤患者不论轻症或重症5项凝血指标的变化均很大,在治疗前后之间和轻重之间的多项比较差异均有统计学意义(P<0.05)。结论银环蛇、眼镜蛇和眼镜王蛇咬伤对凝血功能影响很少;竹叶青蛇咬伤重症患者可引起较严重的凝血功能异常,但治疗后恢复较快;蝰蛇咬伤可引起极大的凝血功能异常,且治疗后恢复慢。%Objective To explore the change regulation of blood coagulation function before and after treatment of snake bite pa‐tients .Methods A total of 226 hospitalized patients with clear diagnosis belong to what kind of snakes in the past two years were selected in this study ,39 cases were bit by coral ,76 cases were bit by trimeresurus stejnegeri ,47 cases were bit by cobra ,24 cases bit by king cobra ,40 cases were bit by adder .Five blood

  7. Effects of calcium signaling on coagulation factor VIIa-induced proliferation and migration of the SW620 colon cancer cell line.

    Science.gov (United States)

    Wu, Ying; Wang, Jing; Zhou, Hong; Yu, Xiaoyan; Hu, Lichao; Meng, Fanlu; Jiang, Shuanghong

    2014-12-01

    Tissue factor (TF)/VIIa/protease‑activated receptor 2 (PAR2) has been shown to trigger the ERK1/2 signaling pathway. This was shown to be closely associated with the proliferation and migration of SW620 colon cancer cells; however, the detailed mechanisms remain unclear. The aim of the present study was to elucidate the effects of calcium signaling on the proliferation and migration of SW620 cells induced by coagulation factor VIIa. The results demonstrated that VIIa and PAR2 agonist PAR2‑AP increased [Ca2+]i in SW620 cells. In addition, VIIa‑and PAR2‑AP‑induced ERK1/2 activation was inhibited by thapsigargin (TG)‑induced depletion of intracellular Ca2+ stores and EGTA‑mediated removal of extracellular Ca2+. It was also identified that VIIa and PAR2‑AP‑induced proliferation and migration of SW620 cells was modulated by EGTA and TG. Taken together, the present results indicate that VIIa triggers calcium signaling in SW620 cells, in a TF‑dependent manner, which is critical for VIIa‑induced ERK1/2 activation in SW620 cells. These results suggested that calcium signaling had a vital role in the proliferation and migration of SW620 cells.

  8. The effects of danaparoid, dalteparin and heparin on tissue factor-induced experimental disseminated intravascular coagulation and bleeding time in the rat.

    Science.gov (United States)

    Miyake, Y; Yokota, K; Fujishima, Y; Sukamoto, T

    2001-07-01

    Danaparoid and heparin, on the basis of anti-activated factor X (anti-FXa) activity, were equipotent in accelerating the rate of interaction of FXa and antithrombin III. In rat tissue factor-induced disseminated intravascular coagulation (DIC) models, an intravenous administration of danaparoid inhibited the decrease in plasma fibrinogen and platelet counts and the increase in serum fibrinogen degradation products. Expressed on the basis of anti-FXa activity, these effects were comparable with those of dalteparin and heparin. In rat mesenteric small artery and vein, less bleeding was observed after intravenous administration of danaparoid than after dalteparin or heparin. Danaparoid did not affect adenosine diphosphate- or collagen-induced platelet aggregation, and showed weaker inhibitory effects on aggregation induced by thrombin, or collagen + thrombin, than did dalteparin or heparin. These findings suggest that danaparoid may be useful for the prevention of DIC and has less tendency to cause bleeding than dalteparin or heparin, probably as a result of its weaker ability to inhibit platelet aggregation. PMID:11505077

  9. In vitro secretion deficits are common among human coagulation factor XIII subunit B missense mutants: correlations with patient phenotypes and molecular models.

    Science.gov (United States)

    Biswas, Arijit; Thomas, Anne; Bevans, Carville G; Ivaskevicius, Vytautas; Oldenburg, Johannes

    2013-11-01

    Coagulation factor XIII (FXIII) proenzyme circulates in plasma as a heterotetramer composed of two each of A and B subunits. Upon activation, the B subunits dissociate from the A subunit dimer, which gains transglutaminase activity to cross-link preformed fibrin clots increasing mechanical strength and resistance to degradation. The B subunits are thought to possess a carrier/protective function before FXIII activation. Mutations in either A or B subunits are associated with pathological patient phenotypes characterized by mild to severe bleeding. In vitro expression of FXIII B subunit (FXIIIB) missense variants in HEK293T cells revealed impaired secretion for all seven variants studied. To investigate the likely molecular environments of the missense residues, we created molecular models of individual FXIIIB Sushi domains using phylogenetically similar complement factor H Sushi domain structural templates. Assessment of the local molecular environments for the models suggested surface or buried positions for each mutant residue and possible pathological mechanisms. The in vitro expression system and in silico analytical methods and models we developed can be used to further investigate the molecular basis of FXIIIB mutation pathologies. PMID:23913518

  10. Synergistic and multidimensional regulation of plasminogen activator inhibitor type 1 expression by transforming growth factor type β and epidermal growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xiaoling; Thalacker, F.W.; Nilsen-Hamilton, Marit

    2012-04-06

    The major physiological inhibitor of plasminogen activator, type I plasminogen activator inhibitor (PAI-1), controls blood clotting and tissue remodeling events that involve cell migration. Transforming growth factor type β (TGFβ) and epidermal growth factor (EGF) interact synergistically to increase PAI-1 mRNA and protein levels in human HepG2 and mink Mv1Lu cells. Other growth factors that activate tyrosine kinase receptors can substitute for EGF. EGF and TGFβ regulate PAI-1 by synergistically activating transcription, which is further amplified by a decrease in the rate of mRNA degradation, the latter being regulated only by EGF. The combined effect of transcriptional activation and mRNA stabilization results in a rapid 2-order of magnitude increase in the level of PAI-1. TGFβ also increases the sensitivity of the cells to EGF, thereby recruiting the cooperation of EGF at lower than normally effective concentrations. The contribution of EGF to the regulation of PAI-1 involves the MAPK pathway, and the synergistic interface with the TGFβ pathway is downstream of MEK1/2 and involves phosphorylation of neither ERK1/2 nor Smad2/3. Synergism requires the presence of both Smad and AP-1 recognition sites in the promoter. This work demonstrates the existence of a multidimensional cellular mechanism by which EGF and TGFβ are able to promote large and rapid changes in PAI-1 expression.

  11. Development of Blood-Brain Barrier Permeable Nitrocatechol-Based Catechol O-Methyltransferase Inhibitors with Reduced Potential for Hepatotoxicity.

    Science.gov (United States)

    Silva, Tiago; Mohamed, Tarek; Shakeri, Arash; Rao, Praveen P N; Martínez-González, Loreto; Pérez, Daniel I; Martínez, Ana; Valente, Maria João; Garrido, Jorge; Uriarte, Eugenio; Serrão, Paula; Soares-da-Silva, Patrício; Remião, Fernando; Borges, Fernanda

    2016-08-25

    Recent efforts have been focused on the development of centrally active COMT inhibitors, which can be valuable assets for neurological disorders such as Parkinson's disease, due to the severe hepatotoxicity risk associated with tolcapone. New nitrocatechol COMT inhibitors based on naturally occurring caffeic acid and caffeic acid phenethyl ester were developed. All nitrocatechol derivatives displayed potent inhibition of peripheral and cerebral COMT within the nanomolar range. Druglike derivatives 13, 15, and 16 were predicted to cross the blood-brain barrier in vitro and were significantly less toxic than tolcapone and entacapone when incubated at 50 μM with rat primary hepatocytes. Moreover, their unique acidity and electrochemical properties decreased the chances of formation of reactive quinone-imines and, as such, the potential for hepatotoxicity. The binding mode of 16 confirmed that the major interactions with COMT were established via the nitrocatechol ring, allowing derivatization of the side chain for future lead optimization efforts.

  12. Gene Therapy for Coagulation Disorders.

    Science.gov (United States)

    Swystun, Laura L; Lillicrap, David

    2016-04-29

    Molecular genetic details of the human coagulation system were among the first successes of the genetic revolution in the 1980s. This information led to new molecular diagnostic strategies for inherited disorders of hemostasis and the development of recombinant clotting factors for the treatment of the common inherited bleeding disorders. A longer term goal of this knowledge has been the establishment of gene transfer to provide continuing access to missing or defective hemostatic proteins. Because of the relative infrequency of inherited coagulation factor disorders and the availability of safe and effective alternative means of management, the application of gene therapy for these conditions has been slow to realize clinical application. Nevertheless, the tools for effective and safe gene transfer are now much improved, and we have started to see examples of clinical gene therapy successes. Leading the way has been the use of adeno-associated virus-based strategies for factor IX gene transfer in hemophilia B. Several small phase 1/2 clinical studies using this approach have shown prolonged expression of therapeutically beneficial levels of factor IX. Nevertheless, before the application of gene therapy for coagulation disorders becomes widespread, several obstacles need to be overcome. Immunologic responses to the vector and transgenic protein need to be mitigated, and production strategies for clinical grade vectors require enhancements. There is little doubt that with the development of more efficient and facile strategies for genome editing and the application of other nucleic acid-based approaches to influence the coagulation system, the future of genetic therapies for hemostasis is bright. PMID:27126652

  13. From Enzyme to Whole Blood: Sequential Screening Procedure for Identification and Evaluation of p38 MAPK Inhibitors.

    Science.gov (United States)

    Bauer, Silke M; Kubiak, Jakub M; Rothbauer, Ulrich; Laufer, Stefan

    2016-01-01

    p38 mitogen-activated protein kinase (MAPK) is a pivotal enzyme in the biosynthesis of pro-inflammatory cytokines like IL-1 and TNF. Therefore, the success of anti-cytokine therapy for treatment of inflammatory processes qualified p38-MAPK as a solid target in drug research concerning chronic inflammatory diseases including infectious vascular, neurobiological, and autoimmune disorders. However, the discovery of new kinase inhibitors is limited by the need for a high biological activity combined with restricted activity to the target enzyme or pathway interaction. As a consequence, no p38 MAPK inhibitor has been introduced to the market so far, although several p38 inhibitors have proceeded into clinical trials. The development of novel inhibitor types and optimization of already known structural classes of MAPK inhibitors require appropriate testing systems reaching across these crucial parameters. As a new approach, we describe the sequential arrangement of three testing systems custom-tailored to the requirements of drug discovery programs with focus on p38 inhibition. Integrated analysis of the obtained results enables a concerted step-by-step selection of tested molecules in order to screen a compound library for the most suitable inhibitor. First, evaluation of the inhibitor's activity on the isolated p38 MAPK enzyme via an ELISA assay gives a first idea about the inhibitory potency of the molecule. Moreover, structure-activity relationships can be elucidated when comparing molecules within inhibitor series. Second, screening in living cells via a p38 substrate-specific MK2-EGFP translocation assay supplies further information about efficacy, but provides also a first notion concerning selectivity and toxicity. Third, efficacy is evaluated more specifically in vivo in LPS-stimulated human whole blood with regard to in vivo parameters, e.g., pharmacokinetic characteristics like plasma protein binding and cellular permeability. These three testing systems

  14. The role of platelets in coagulation dysfunction in xenotransplantation, and therapeutic options.

    Science.gov (United States)

    Iwase, Hayato; Ezzelarab, Mohamed B; Ekser, Burcin; Cooper, David K C

    2014-01-01

    Xenotransplantation could resolve the increasing discrepancy between the availability of deceased human donor organs and the demand for transplantation. Most advances in this field have resulted from the introduction of genetically engineered pigs, e.g., α1,3-galactosyltransferase gene-knockout (GTKO) pigs transgenic for one or more human complement-regulatory proteins (e.g., CD55, CD46, CD59). Failure of these grafts has not been associated with the classical features of acute humoral xenograft rejection, but with the development of thrombotic microangiopathy in the graft and/or consumptive coagulopathy in the recipient. Although the precise mechanisms of coagulation dysregulation remain unclear, molecular incompatibilities between primate coagulation factors and pig natural anticoagulants exacerbate the thrombotic state within the xenograft vasculature. Platelets play a crucial role in thrombosis and contribute to the coagulation disorder in xenotransplantation. They are therefore important targets if this barrier is to be overcome. Further genetic manipulation of the organ-source pigs, such as pigs that express one or more coagulation-regulatory genes (e.g., thrombomodulin, endothelial protein C receptor, tissue factor pathway inhibitor, CD39), is anticipated to inhibit platelet activation and the generation of thrombus. In addition, adjunctive pharmacologic anti-platelet therapy may be required. The genetic manipulations that are currently being tested are reviewed, as are the potential pharmacologic agents that may prove beneficial.

  15. 基于锥板磁珠法的全自动凝血分析仪应用评价%Based on the Cone Board Magnetic Beads Method of the Full-Automatic Blood Coagulation Analyzer Application Evaluation

    Institute of Scientific and Technical Information of China (English)

    王海; 邸平; 乐家新; 李健

    2012-01-01

    目的 评价Destiny Max全自动凝血分析仪的性能.方法 结合全自动凝血分析仪国家行业标准检测Destiny Max全自动凝血分析仪的精密度、线性范围、携带污染率、可比性、抗干扰能力以及Fbg检出限值.结果 批内精密度PT、INR、aPTF、Fbg、TT、D二聚体正常质控CV值分别为:1.61、1.98、1.91、1.48、1.15、12.76;异常质控CV值分别为:0.90、1.20、0.44、3.70、0.31、5.41;批间精密度正常质控CV值分别为:1.54、1.98、1.77、0.89、1.15、15.90;批间精密度异常质控CV值分别为:0.52、0.80、0.40、2.75、0.53、5.25.Fbg试剂携带污染率为1.08%;PT、INR、aPTT、Fbg、TT测定结果在与法国STA-R凝血分析仪器上密切相关,r值分别为:0.995、0.995、0.947、0.962、0.984,D二聚体与法国STA-R的D二聚体相比阳性符合率96.9%;在抗干扰能力上不受黄疸、乳糜、溶血、混浊等光学干扰物对检测的干扰;线性范围较宽.结论 Destiny Max全自动凝血分析仪各项性能精确,机器结构严谨,设计合理,测试速度较快,操作简便.可以对临床血液分析做出快速准确的报告.%Objective To evaluate the Destiny Max full-automatic blood coagulation analyzer performance. Methods Combination of full-automatic blood coagulation analyzer national industry standards for detecting the Destiny Max full- automatic blood coagulation analyzer precision, linear range, carry contamination rate,comparability and anti-interference ability,as well as FIB detection limit value. Results Intra-assay precision of PT,INR,aPTT,Fbg,TT,D- dimer of normal quality control CV values are; 1. 61,1. 98,1.91,1.48, 1.15,12.76;The abnormal quality control CV values are:0. 90,1. 20,0. 44,3. 70,0. 31,5. 41. Inter-assay precision of PT, INR, aPTT, Fbg ,TT, D- dimer of normal quality control CV values are: 1. 54,1. 98,1. 77, 0.89,1.15,15.90;The abnormal quality control CV values are:0. 52,0. 80,0.40,2.75,0.53,5.25 ;The carry contamination

  16. Risk factors for hepatitis B carrier status among blood donors of the National Blood Center, Thai Red Cross Society.

    Science.gov (United States)

    Nuchprayoon, T; Chumnijarakij, T

    1992-06-01

    A study of risk factors for hepatitis B carriers among voluntary blood donors of the National Blood Center, Thai Red Cross Society was carried out in a case-control study design during January 1989 to June 1990. Cases were 876 blood donors whose blood identified HBsAg at time of recruitment and continued positive for more than 6 months. Controls were 1,750 blood donors whose blood was free from HBsAg who came for blood donation at the same period as the cases. The ratio of cases:controls = 1:2. Self-administered questionnaires were constructed and pretested before using both cases and controls. The study revealed that the risk factors for hepatitis B among voluntary blood donors were age of less than 30 years old; low socioeconomic status (family income of less than 8,000 Baht/month); single status, especially males; male occupations of students, monks, nongovernment workers compared with government officials; female occupations of laborers, students, nongovernment workers and government officials compared with housewives. Sharing of nail clippers, used blades and tooth brushes among family members are proved to be risk factors, especially among males. In addition, sharing of used blades in barber shops proved to be a risk among males while sharing of nail clippers in beauty salons, history of ear-piercing at department stores or history of caesarean section among females could not be shown to be risk factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1439976

  17. The Interface between Inflammation and Coagulation in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Gabriele Demetz

    2012-01-01

    Full Text Available The intimate connection between coagulation and inflammation in the pathogenesis of vascular disease has moved more and more into focus of clinical research. This paper focuses on the essential components of this interplay in the settings of cardiovascular disease and acute coronary syndrome. Tissue factor, the main initiator of the extrinsic coagulation pathway, plays a central role via causing a proinflammatory response through activation of coagulation factors and thereby initiating coagulation and downstream cellular signalling pathways. Regarding activated clotting factors II, X, and VII, protease-activated receptors provide the molecular link between coagulation and inflammation. Hereby, PAR-1 displays deleterious as well as beneficial properties. Unravelling these interrelations may help developing new strategies to ameliorate the detrimental reciprocal aggravation of inflammation and coagulation.

  18. Beneficial effect of treatment with a monoclonal anti-tumor necrosis factor-alpha antibody on markers of coagulation and fibrinolysis in patients with active Crohn's disease

    NARCIS (Netherlands)

    Hommes, DW; van Dullemen, HM; Levi, M; Van der Ende, A; Woody, J; Tytgat, GNJ; van Deventer, SJH

    1997-01-01

    Crohn's disease has frequently been associated with coagulation abnormalities, causing intravascular deposition of fibrin and local infarction which can subsequently compromise the gut mucosa. Also, arterial and venous thromboembolic complications of larger vessels appear to be associated with Crohn

  19. Identification of inflammatory factor TNFα inhibitor from medicinal herbs.

    Science.gov (United States)

    Ye, Hong; Wang, Yali; Jenson, A Bennett; Yan, Jun

    2016-04-01

    The inflammatory response is one of the first defenses our body has to fight against potential endangerments. It plays a critical role in host defense, clearing and slowing the infection in the case of microbial invasion. During an inflammatory response, a variety of cytokines are produced by cells and trigger or enhance the specific inflammation response. TNFα, one of these factors, plays a crucial role in many immune and inflammatory processes, such as proliferation, apoptosis, necrosis, and cell survival. It acts in orchestrating the cytokine cascade and the major regulator of inflammatory cytokine production. Abnormality of TNFα signaling leads to many diseases, including rheumatoid arthritis, psoriasis, Crohn's disease, atherosclerosis, and cancer. Due to the importance of TNFα, regulating TNFα activity is a key to treat the related diseases. There is a long history of using medicinal herbs to treat diseases related to inflammation. We searched for an ingredient that has the ability to inhibit TNFα, we examined AO herbal extract, containing 10 individual herbs and most of these herbs have anti-inflammatory activity within humans. We have tested the anti-inflammatory ability of AO herbal extract on mice. Furthermore, we used macrophage cell from young mice and found that AO extract has the ability to reduce the inflammation by inhibiting TNFα level. PMID:26778692

  20. Dabigatran and its reversal with recombinant factor VIIa and prothrombin complex concentrate

    DEFF Research Database (Denmark)

    Sølbeck, Sacha; Nilsson, Caroline U; Engström, Martin;

    2014-01-01

    OBJECTIVE: Dabigatran is a new oral direct thrombin inhibitor. No specific antidote exists in the event of hemorrhage, but prothrombin complex concentrate (PCC) and recombinant activated factor VII (rFVIIa) are suggested therapies. Sonoclot is a bedside viscoelastic instrument for monitoring...... the coagulation process in whole blood. The aim of this study was to investigate the effect of dabigatran and reversal with PCC and rFVIIa, as monitored by the Sonoclot. METHODS: Citrated whole blood was drawn and mixed in vitro with dabigatran, dabigatran + PCC or dabigatran + rFVIIa and analyzed with three...... different Sonoclot cuvettes: Glassbead, kaolin and tissue factor (diluted) activated. RESULTS: The Sonoclot detected in vitro-induced anticoagulation due to dabigatran with the glassbead- and kaolin-activated cuvettes. There was no reversing effect of PCC, probably due to the presence of heparin in the PCC...

  1. Accentuating and Opposing Factors Leading to Development of Thoracic Aortic Aneurysms Not Due to Genetic or Inherited Conditions.

    Science.gov (United States)

    Rabkin, Simon W

    2015-01-01

    Understanding and unraveling the pathophysiology of thoracic aortic aneurysm (TAA), a vascular disease with a potentially high-mortality rate, is one of the next frontiers in vascular biology. The processes leading to the formation of TAA, of unknown cause, so-called degenerative TAA, are complex. This review advances the concept of promoters and inhibitors of the development of degenerative TAA. Promoters of TAA development include age, blood pressure elevation, increased pulse pressure, neurohumeral factors increasing blood pressure, inflammation specifically IFN-γ, IL-1 β, IL-6, TNF-α, and S100 A12; the coagulation system specifically plasmin, platelets, and thrombin as well as matrix metalloproteinases (MMPs). SMAD-2 signaling and specific microRNAs modulate TAA development. The major inhibitors or factors opposing TAA development are the constituents of the aortic wall (elastic lamellae, collagen, fibulins, fibronectin, proteoglycans, and vascular smooth muscle cells), which maintain normal aortic dimensions in the face of aortic wall stress, specific tissue MMP inhibitors, plasminogen activator inhibitor-1, protease nexin-1, and Syndecans. Increases in promoters and reductions in inhibitors expand the thoracic aorta leading to TAA formation. PMID:26664893

  2. Microbes bind complement inhibitor factor H via a common site.

    Directory of Open Access Journals (Sweden)

    T Meri

    Full Text Available To cause infections microbes need to evade host defense systems, one of these being the evolutionarily old and important arm of innate immunity, the alternative pathway of complement. It can attack all kinds of targets and is tightly controlled in plasma and on host cells by plasma complement regulator factor H (FH. FH binds simultaneously to host cell surface structures such as heparin or glycosaminoglycans via domain 20 and to the main complement opsonin C3b via domain 19. Many pathogenic microbes protect themselves from complement by recruiting host FH. We analyzed how and why different microbes bind FH via domains 19-20 (FH19-20. We used a selection of FH19-20 point mutants to reveal the binding sites of several microbial proteins and whole microbes (Haemophilus influenzae, Bordetella pertussis, Pseudomonas aeruginosa, Streptococcus pneumonia, Candida albicans, Borrelia burgdorferi, and Borrelia hermsii. We show that all studied microbes use the same binding region located on one side of domain 20. Binding of FH to the microbial proteins was inhibited with heparin showing that the common microbial binding site overlaps with the heparin site needed for efficient binding of FH to host cells. Surprisingly, the microbial proteins enhanced binding of FH19-20 to C3b and down-regulation of complement activation. We show that this is caused by formation of a tripartite complex between the microbial protein, FH, and C3b. In this study we reveal that seven microbes representing different phyla utilize a common binding site on the domain 20 of FH for complement evasion. Binding via this site not only mimics the glycosaminoglycans of the host cells, but also enhances function of FH on the microbial surfaces via the novel mechanism of tripartite complex formation. This is a unique example of convergent evolution resulting in enhanced immune evasion of important pathogens via utilization of a "superevasion site."

  3. 弥散性血管内凝血的治疗%Therapy for disseminated intravascular coagulation

    Institute of Scientific and Technical Information of China (English)

    飞球; 麦惠容

    2015-01-01

    Disseminated intravascular coagulation ( DIC ) is a exceedingly complicated pathophysiological process,both pro and anti coagulation factors are activated and consumed,it is difficult to determine acute stage of the syndrome for physicians based on clinical presentations and laboratory tests,management strategy of DIC is not same due to different etiology,the dose and regimen of drug administration are uncertain. At present pediatricians usually treat children patients with DIC according to researches and guidelines for adults. The key strategies to DIC management is to treat underlying diseases aggressively so as to clear risk factors triggering extensive coagulation and resuscitate with ap-propriate blood products. No clinical trials have proved that heparin can improve clinical outcome,efficacies of activated protein C,antithrombin, tissue factor pathway inhibitor and thrombomodulin are needed to be verified by more high qua-lity clinical trials in DIC treatment.%弥散性血管内凝血( DIC)是一个非常复杂的病理生理过程,促凝和抗凝因子及血小板均有消耗,根据临床表现和实验室检查很难准确判断疾病的真实临床进程,处理上常常需要结合所在医院习惯和专家的经验。不同类型DIC的处理、用药的剂量与方案存在诸多的不确定性。有关DIC的治疗,儿科目前主要参考成人的指南。DIC最重要的处理措施是对潜在疾患进行强有力的治疗,消除触发凝血病变危险因素,同时采用恰当的血液制品进行复苏。尚无临床随机试验证实应用肝素在DIC患者能改善临床相关结果,活化蛋白C、抗凝血酶、组织因子通路抑制物和血栓调节素等抗凝因子在DIC治疗中的意义还有待于更多高质量的临床研究深入探讨。

  4. Effects of the non-selective phosphodiesterase inhibitor pentoxifylline on regional cerebral blood flow and large arteries in healthy subjects

    DEFF Research Database (Denmark)

    Kruuse, Christina; Jacobsen, T B; Thomsen, Lars Lykke;

    2000-01-01

    The vasodilating properties of the non-selective phosphodiesterase (PDE) inhibitor pentoxifylline were evaluated. Pentoxifylline has been reported to increase cerebral blood flow (CBF) and improve recovery rate of stroke patients. Whether these results are due to a dilating effect on arteries...... or to other mechanisms is not clear. In the present double-blind crossover study, 10 healthy subjects received pentoxifylline 300 mg or placebo intravenously on separate days. Blood flow velocity in the middle cerebral artery (V(mca)) was recorded by transcranial Doppler and rCBF was measured using (133)Xenon...... dilatation of the large arteries. However, this change was not significantly different from placebo. In conclusion, pentoxifylline 300 mg had no effect on rCBF. A possible minor dilatation of the middle cerebral artery and the temporal artery cannot be excluded. Any potential clinical effect...

  5. Teleworking in United Arab Emirates (UAE): An empirical study of influencing factors, facilitators, and inhibitors

    OpenAIRE

    Elamin, A.M.; Aboelmaged, M.G.

    2009-01-01

    This research constitutes an empirical study of influencing factors, facilitators, and inhibitors to the choice of teleworking mode in the UAE context. The research reveals that gender, marital status, nationality, residence location, and work profession are relevant, whereas educational level, Internet use, number of children, age, and years of experience are irrelevant influencing factors for the choice of teleworking mode. Furthermore, the research identifies six distinct facilitators and ...

  6. Use of snake venom fractions in the coagulation laboratory.

    Science.gov (United States)

    Marsh, N A

    1998-07-01

    Snake venom toxins are now regularly used in the coagulation laboratory for assaying haemostatic parameters and as coagulation reagents. Snake venom thrombin-like enzymes (SVTLE) are used for fibrinogen and fibrinogen breakdown product assay as well as detecting dysfibrinogenaemias. Significantly, because SVTLE are not inhibited by heparin, they can be used for defibrinating samples that contain the anticoagulant before assay of haemostatic variables. Prothrombin activators are found in many snake venoms and are used in prothrombin assays, for studying dysprothrombinaemias and preparing meizothrombin and non-enzymic prothrombin. Russell's viper (Daboia russelli) venom (RVV) contains a number of compounds useful in the assay of factors V, VII, X, platelet factor 3 and lupus anticoagulants. Activators from the taipan, Australian brown snake and saw-scaled viper have been used to assay lupus anticoagulants. Protein C and activated protein C resistance can be measured by means of RVV and Protac, a fast acting inhibitor from Southern copperhead snake venom and von Willebrand factor can be studied with Botrocetin from Bothrops jararaca venom. Finally, phospholipase A2 enzymes and the disintegrins, a family of Arg-Gly-Asp (RGD)-containing proteins found in snake venoms, show great potential for the study of haemostasis including, notably, platelet glycoprotein receptors GPIIb/IIIa and Ib. PMID:9712287

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

    Energy Technology Data Exchange (ETDEWEB)

    Maliaritsi, E. [Laboratory of Physical Metallurgy, School of Mining and Metallurgy Engineering, National Technical University of Athens, Zografou Campus, Athens 15780 (Greece); Zoumpoulakis, L. [Laboratory of Materials Science and Technology, Inter-disciplinary Postgraduate Programme of NTUA, School of Chemical Engineering, National Technical University of Athens, Zografou Campus, 157 73 Athens (Greece); Simitzis, J. [Laboratory of Materials Science and Technology, Inter-disciplinary Postgraduate Programme of NTUA, School of Chemical Engineering, National Technical University of Athens, Zografou Campus, 157 73 Athens (Greece); Vassiliou, P. [Iaso General Hospital, Athens (Greece); Hristoforou, E. [Laboratory of Physical Metallurgy, School of Mining and Metallurgy Engineering, National Technical University of Athens, Zografou Campus, Athens 15780 (Greece)]. E-mail: eh@metal.ntua.gr

    2006-04-15

    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.

  8. Kinetics of CLL cells in tissues and blood during therapy with the BTK inhibitor ibrutinib

    OpenAIRE

    Wodarz, Dominik; Garg, Naveen; Komarova, Natalia L.; Benjamini, Ohad; Keating, Michael J.; Wierda, William G.; Kantarjian, Hagop; James, Danelle; O’Brien, Susan; Burger, Jan A.

    2014-01-01

    During ibrutinib therapy, 1.7% of blood and 2.7% of tissue CLL cells die per day which is 3 and 5 times higher than without treatment.The fraction of CLL cells that redistribute into the blood during ibrutinib treatment represents 23.3% ± 17% of the tissue disease burden.

  9. Effects of the Bracts and Bars of Zea mays L.on Blood Coagulation%玉蜀黍轴及苞叶对凝血作用的影响

    Institute of Scientific and Technical Information of China (English)

    顾海鹏; 周大鹏; 顾雪竹; 康文艺

    2013-01-01

    The effect of extracts of the bracts and bars of Zea mays L.on blood coagulation was investigated using Vitamin K1 as coagulant control and breviscapine as anti-coagulant control.Petroleum ether,ethyl acetate and n-butanol extracts of Z.mays bracts and bars and the total methanol extract of bracts were assayed using plasma recalcification time method in vitro.n-Butanol extract of bars and ethyl acetate extract of bract significantly reduced the plasma recalcificatio