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Sample records for blood coagulation factor inhibitors

  1. Tissue factor pathway inhibitor-alpha inhibits prothrombinase during the initiation of blood coagulation

    OpenAIRE

    Wood, Jeremy P.; Bunce, Matthew W.; Maroney, Susan A.; Tracy, Paula B.; Camire, Rodney M.; Mast, Alan E.

    2013-01-01

    The generation of thrombin by prothrombinase, a complex composed of activated (a) factors X (FXa) and V (FVa), is a final step in blood coagulation. We demonstrate that tissue factor pathway inhibitor (TFPI) blocks thrombin generation by prothrombinase at physiologically relevant rates and concentrations, but only during the initiation of clot formation. TFPI mediates this inhibitory activity through two high-affinity interactions, one with FXa and one with FVa. This is the first description ...

  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. 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 pat...

  4. Blood Clotting and Coagulation Factors: The Work of Yale Nemerson

    OpenAIRE

    Kresge, Nicole; Simoni, Robert D.; Hill, Robert L.

    2011-01-01

    After developing a blood disorder, Yale Nemerson became interested in hematology. This led to his lifelong study of thrombogenic tissue factor and to his contributions to developing the modern theory of blood coagulation. The two Classic papers reprinted here detail some of Nemerson's studies on coagulation factors IX and VII.

  5. 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.

  6. Coagulation factors in whole blood collected from pregnant women and stored at 4°C

    OpenAIRE

    Minatoguchi, Miki; ITAKURA, ATSUO; Miki, Akinori; Kajihara, Takeshi; Sasaki, Shiho; Takase, Yumiko; Kobayashi, Kiyoko; Asada, Rumiko; IKEBUCHI, KENJI; Ishihara, Osamu

    2016-01-01

    ABSTRACT The present study aimed to measure the levels of coagulation factors in stored whole blood of pregnant women and to determine their usefulness in treating pregnant women who developed coagulopathy. A prospective study to measure coagulation factors in stored donated whole blood from pregnant and non-pregnant women was conducted. Fibrinogen, FV, FVII, FVIII, FXIII, and von Willebrand factor were measured in blood stored at 4°C for 0, 1, 3, and 5 weeks. All coagulation factors except f...

  7. Coagulation Factors Test

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Coagulation Factors Share this page: Was this page helpful? ... if a person has a sufficient amount of coagulation activity in order to control the blood clotting ...

  8. Inhibitors against the coagulation factors spontaneously acquired: Acquired B Hemophilia

    OpenAIRE

    Claudia Lucía Sossa Melo; Sara Inés Jiménez Sanguino; Pilar Rodríguez

    2003-01-01

    Spontaneously acquired inhibitors to factor IX, are extremely rare. A 70-year-old male, presented with major continuous post-orthopedic surgery bleeding. His initial APTT was 77.4 s (normal range, 25-36) and normal PT. Expanded APTT corrects, results in favor of deficit of factor IX, confirming the level of dose of IX factor: 52% (NR 70–125%) with normal factor VIII. It was realized with fresh frozen plasma, and by the fifth day of treatment, he presents a bruise in the surgery bed with radic...

  9. Localization of blood coagulation factors in the germinal centers of human Peyer's patches

    OpenAIRE

    Kudo, S.; Yamakawa, Mitsunori; Imai, Yutaka; Tsukamoto, M.

    1992-01-01

    The immunohistochemical distribution of 15 blood coagulation factors in the germinal centers (GCs) of human Peyer's patches (PPs) was studied. Although factor VIII, active alpha-thrombin, and fibrinogen were hardly evident in the GCs, the majority of coagulation factors, such as kallikrein, high-molecular-weight kininogen, factos XII, X, IX, VII, V, XIIIa and XIIIb, prothrombin, anti-thrombin 111 and inactive alpha-thrombin were found, showing a lace-like s...

  10. Targeting exosites on blood coagulation proteases

    OpenAIRE

    Monteiro, Robson Q.

    2005-01-01

    The high specificity of blood coagulation proteases has been attributed not only to residues surrounding the active site but also to other surface domains that are involved in recognizing and interacting with macromolecular substrates and inhibitors. Specific blood coagulation inhibitors obtained from exogenous sources such as blood sucking salivary glands and snake venoms have been identified. Some of these inhibitors interact with exosites on coagulation enzymes. Two examples are discussed ...

  11. PHYSIOLOGY OF BLOOD COAGULATION

    OpenAIRE

    B. Ţuţuianu

    2007-01-01

    Untill the XIXth century we knew very little about coagulation and haemostasis, most of our knowledge being based on observations. The discovery of thrombin, platelets, fibrinogen and calcium led to one of the most important theories (Paul Moravitz, 1890), which gave a scientific explanation of the haemostasis, describing the main steps of coagulation. Further on, the discovery of coagulation factors, of vitamin K, of heparin and of coagulation tests offered the ground for a new theory, namel...

  12. A high-fat meal does not activate blood coagulation factor VII in minipigs

    DEFF Research Database (Denmark)

    Olsen, A K; Larsen, L F; Bladbjerg, E-M; Hansen, A K; Jespersen, J; Marckmann, P

    2001-01-01

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

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

    International Nuclear Information System (INIS)

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

  14. Blood flow controls coagulation onset via the positive feedback of factor VII activation by factor Xa

    OpenAIRE

    Panteleev Mikhail A; Lobanova Ekaterina S; Shibeko Alexey M; Ataullakhanov Fazoil I

    2010-01-01

    Abstract Background Blood coagulation is a complex network of biochemical reactions, which is peculiar in that it is time- and space-dependent, and has to function in the presence of rapid flow. Recent experimental reports suggest that flow plays a significant role in its regulation. The objective of this study was to use systems biology techniques to investigate this regulation and to identify mechanisms creating a flow-dependent switch in the coagulation onset. Results Using a detailed mech...

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

    International Nuclear Information System (INIS)

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

  16. Novel aspects of blood coagulation factor XIII. I. Structure, distribution, activation, and function

    Energy Technology Data Exchange (ETDEWEB)

    Muszbek, L.; Adany, R. [Univ. Medical School of Debrecen (Hungary); Mikkola, H. [Univ. of Helsinki (Finland)

    1996-10-01

    Blood coagulation factor XIII (FXIII) is a protransglutaminase that becomes activated by the concerted action of thrombin and Ca{sup 2+} in the final stage of the clotting cascade. In addition to plasma, FXIII also occurs in platelets, monocytes, and monocyte-derived macrophages. While the plasma factor is a heterotetramer consisting of paired A and B subunits (A{sub 2}B{sub 2}), its cellular counterpart lacks the B subunits and is a homodimer of potentially active A subunits (A{sub 2}). The gene coding for the A and B subunits has been localized to chromosomes 6p24-25 and 1q31-32.1, respectively. The genomic as well as the primary protein structure of both subunits has been established. Plasma FXIII circulates in association with its substrate precursor, fibrinogen. Fibrin(ogen) has an important regulatory role in the activation of plasma FXIII, for instance the proteolytic removal of activation peptide by thrombin, the dissociation of subunits A and B, and the exposure of the originally buried active site on the free A subunits. The end result of this process is the formation of an active transglutaminase, which crosslinks peptide chains through {epsilon}({gamma}-glutamyl)lysyl isopeptide bonds. The protein substrates of activated FXIII include components of the clotting-fibrinolytic system, adhesive and contractile proteins. The main physiological function of plasma FXIII is to cross-link fibrin and protect it from the fibrinolytic enzyme plasmin. The latter effect is achieved mainly by covalently linking {alpha}{sub 2} antiplasmin, the most potent physiological inhibitor of plasmin, to fibrin. Plasma FXIII seems to be involved in wound healing and tissue repair, and it is essential to maintaining pregnancy. Cellular FXIII, if exposed to the surface of the cells, might support or perhaps take over the hemostatic functions of plasma FXIII; however, its intracellular role has remained mostly unexplored. 328 refs., 4 figs.

  17. A novel coagulation inhibitor from Schistosoma japonicum.

    Science.gov (United States)

    Ranasinghe, Shiwanthi L; Fischer, Katja; Gobert, Geoffrey N; McManus, Donald P

    2015-12-01

    Little is known about the molecular mechanisms whereby the human blood fluke Schistosoma japonicum is able to survive in the host venous blood system. Protease inhibitors are likely released by the parasite enabling it to avoid attack by host proteolytic enzymes and coagulation factors. Interrogation of the S. japonicum genomic sequence identified a gene, SjKI-1, homologous to that encoding a single domain Kunitz protein (Sjp_0020270) which we expressed in recombinant form in Escherichia coli and purified. SjKI-1 is highly transcribed in adult worms and eggs but its expression was very low in cercariae and schistosomula. In situ immunolocalization with anti-SjKI-1 rabbit antibodies showed the protein was present in eggs trapped in the infected mouse intestinal wall. In functional assays, SjKI-1 inhibited trypsin in the picomolar range and chymotrypsin, neutrophil elastase, FXa and plasma kallikrein in the nanomolar range. Furthermore, SjKI-1, at a concentration of 7·5 µ m, prolonged 2-fold activated partial thromboplastin time of human blood coagulation. We also demonstrate that SjKI-1 has the ability to bind Ca(++). We present, therefore, characterization of the first Kunitz protein from S. japonicum which we show has an anti-coagulant properties. In addition, its inhibition of neutrophil elastase indicates SjKI-1 have an anti-inflammatory role. Having anti-thrombotic properties, SjKI-1 may point the way towards novel treatment for hemostatic disorders. PMID:26463744

  18. Positive selection during the evolution of the blood coagulation factors in the context of their disease-causing mutations

    OpenAIRE

    Rallapalli, P. M.; Orengo, C A; Studer, R. A.; Perkins, S. J.

    2014-01-01

    Blood coagulation occurs through a cascade of enzymes and cofactors that produces a fibrin clot, while otherwise maintaining hemostasis. The 11 human coagulation factors (FG, FII–FXIII) have been identified across all vertebrates, suggesting that they emerged with the first vertebrates around 500 Ma. Human FVIII, FIX, and FXI are associated with thousands of disease-causing mutations. Here, we evaluated the strength of selective pressures on the 14 genes coding for the 11 factors during verte...

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    Ever since the coagulant activity of blood coagulation factor VII (FVII:C) was identified as a risk indicator of cardiac death, a large number of studies have measured FVII protein concentrations in plasma. FVII protein concentrations are either measured immunologically with an ELISA method (FVII......:Ag) or estimated with an amidolytic method (FVII:Am). We have investigated whether FVII:Am is a valuable alternative to FVII:Ag. FVII:Ag and FVII:Am were measured in 147 plasma samples from blood donors, patients on oral anticoagulant therapy, postmenopausal women on hormone replacement therapy, in...... after 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 < 0.01). In a linear regression analysis, the intercept (alpha=-21.50) was different from zero (p < 0.0001) and the slope (beta=1.16) was different from 1.0 (p < 0...

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

    OpenAIRE

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

    2013-01-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation f...

  1. 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; Svergun, Dmitri I; Bukrinsky, Jens Thostrup; Vestergaard, Bente

    2010-01-01

    Blood coagulation factor VIIa (FVIIa) is used in the treatment of replacement therapy resistant hemophilia patients, and FVIIa is normally activated upon complex formation with tissue factor (TF), potentially in context with structural rearrangements. The solution behavior of uncomplexed FVIIa is...

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2013-06-01

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

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

    International Nuclear Information System (INIS)

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

  5. 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...

  6. 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

  7. 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.

  8. Targeting exosites on blood coagulation proteases

    Directory of Open Access Journals (Sweden)

    Robson Q. Monteiro

    2005-06-01

    Full Text Available The high specificity of blood coagulation proteases has been attributed not only to residues surrounding the active site but also to other surface domains that are involved in recognizing and interacting with macromolecular substrates and inhibitors. Specific blood coagulation inhibitors obtained from exogenous sources such as blood sucking salivary glands and snake venoms have been identified. Some of these inhibitors interact with exosites on coagulation enzymes. Two examples are discussed in this short revision. Bothrojaracin is a snake venom-derived protein that binds to thrombin exosites 1 and 2. Complex formation impairs several exosite-dependent activities of thrombin including fibrinogen cleavage and platelet activation. Bothrojaracin also interacts with proexosite 1 on prothrombin thus decreasing the zymogen activation by the prothrombinase complex (FXa/FVa. Ixolaris is a two Kunitz tick salivary gland inhibitor, that is homologous to tissue factor pathway inhibitor. Recently it was demonstrated that ixolaris binds to heparin-binding exosite of FXa, thus impairing the recognition of prothrombin by the enzyme. In addition, ixolaris interacts with FX possibly through the heparin-binding proexosite. Differently from FX, the ixolaris-FX complex is not recognized as substrate by the intrinsic tenase complex (FIXa/FVIIIa. We conclude that these inhibitors may serve as tools for the study of coagulation exosites as well as prototypes for new anticoagulant drugs.A alta especificidade das proteases da coagulação tem sido atribuída não somente aos resíduos que cercam o sítio ativo, mas também a outros domínios de superfície que estão envolvidos no reconhecimento e interação com substratos macromoleculares e inibidores. Inibidores específicos da coagulação sanguínea obtidos de fontes exógenas como glândulas salivares de animais hematófagos e venenos de serpentes têm sido identificados. Alguns desses inibidores interagem com os

  9. 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

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

    OpenAIRE

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

    1984-01-01

    The kinetics of activation of human Factor IX by human Factor XIa was studied by measuring the release of a trichloroacetic acid-soluble tritium-labeled activation peptide from Factor IX by a modification of a method described for bovine Factor IX activation by Zur and Nemerson (Zur, M., and Y. Nemerson, 1980, J. Biol. Chem., 255:5703-5707). Initial rates of trichloroacetic acid-soluble 3H-release were linear over 10-30 min of incubation of Factor IX (88 nM) with CaCl2 (5 mM) and with pure (g...

  11. Nanoparticles and the blood coagulation system. Part II: safety concerns

    OpenAIRE

    Ilinskaya, Anna N; Dobrovolskaia, Marina A.

    2013-01-01

    Nanoparticle interactions with the blood coagulation system can be beneficial or adverse depending on the intended use of a nanomaterial. Nanoparticles can be engineered to be procoagulant or to carry coagulation-initiating factors to treat certain disorders. Likewise, they can be designed to be anticoagulant or to carry anticoagulant drugs to intervene in other pathological conditions in which coagulation is a concern. An overview of the coagulation system was given and a discussion of a des...

  12. 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)...

  13. 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

  14. 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...

  15. 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)

  16. 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.

  17. 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...

  18. 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

  19. 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...

  20. Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation

    OpenAIRE

    Kang, Yoo Goo; Martin, Douglas J.; Marquez, Jose; Lewis, Jessica H.; Bontempo, Franklin A.; Shaw, Byers W.; Starzl, Thomas E.; Winter, Peter M.

    1985-01-01

    The blood coagulation system of 66 consecutive patients undergoing consecutive liver transplantations was monitored by thrombelastograph and analytic coagulation profile. A poor preoperative coagulation state, decrease in levels of coagulation factors, progressive fibrinolysis, and whole blood clot lysis were observed during the preanhepatic and anhepatic stages of surgery. A further general decrease in coagulation factors and platelets, activation of fibrinolysis, and abrupt decrease in leve...

  1. 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...

  2. Coagulation Factor Binding Orientation and Dimerization May Influence Infectivity of Adenovirus-Coagulation Factor Complexes

    OpenAIRE

    Irons, Eric E.; Flatt, Justin W.; Doronin, Konstantin; Fox, Tara L.; Acchione, Mauro; Stewart, Phoebe L.; Shayakhmetov, Dmitry M.

    2013-01-01

    Adenoviruses (Ads) are promising vectors for therapeutic interventions in humans. When injected into the bloodstream, Ad vectors can bind several vitamin K-dependent blood coagulation factors, which contributes to virus sequestration in the liver by facilitating transduction of hepatocytes. Although both coagulation factors FVII and FX bind the hexon protein of human Ad serotype 5 (HAdv5) with a very high affinity, only FX appears to play a role in mediating Ad-hepatocyte transduction in vivo...

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

    OpenAIRE

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

    2014-01-01

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

  4. Silica Nanoparticles Effects on Blood Coagulation Proteins and Platelets

    OpenAIRE

    Volodymyr Gryshchuk; Natalya Galagan

    2016-01-01

    Interaction of nanoparticles with the blood coagulation is important prior to their using as the drug carriers or therapeutic agents. The aim of present work was studying of the primary effects of silica nanoparticles (SiNPs) on haemostasis in vitro. We studied the effect of SiNPs on blood coagulation directly estimating the activation of prothrombin and factor X and to verify any possible effect of SiNPs on human platelets. It was shown that SiNPs shortened coagulation time in APTT and PT te...

  5. 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?”.

  6. 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...

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

    International Nuclear Information System (INIS)

    To investigate the effect of continuous positive airway pressure ventilation (CPAP) on platelet-activating factor (PAF) expression and blood coagulation function in patients with obstructive sleep apnea-hypopnea syndrome (OSAS), the blood sample of 40 patients with OSAS were taken before treatment and on the day 30 after treatment respectively. PAF, thromboxane B2 (TXB2), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrin(FIB) in patients and 37 health controls were detected. The results showed that PAF, TXB2, FIB in OSAS patients before treatment were significantly higher than those of after treatment and control group (P0.05). There were abnormal expression of PAF and hypercoagulability in OSAS patients. CPAP could effectively decrease the expression of PAF, TXB2 and could also correct dysfunction of blood coagulation. It had certain effect in lightening the clinical symptoms in OSAS patients. (authors)

  8. 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...

  9. 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.

  10. Coagulation in liver toxicity and disease: Role of hepatocyte tissue factor

    OpenAIRE

    Kopec, Anna K.; Luyendyk, James P.

    2014-01-01

    The liver is the primary source of a number of circulating coagulation factors, and acute liver injury and chronic liver disease are each associated with alterations in blood coagulation. Current views of the connection between liver injury and coagulation extend beyond the impact of liver disease on synthesis of coagulation factors to include a role for coagulation factor activity in the initiation and progression of liver disease. Mechanisms of coagulation initiation in liver disease are no...

  11. Blood coagulation and its alterations in hemorrhagic and thrombotic disorders.

    OpenAIRE

    Rapaport, S I

    1993-01-01

    Clinical observations have added to the understanding of basic mechanisms of blood coagulation and its alterations in certain hemorrhagic and thrombotic states. Much clinical evidence exists for concluding that the exposure of blood to tissue factor (thromboplastin) on tissue cells represents the key event initiating fibrin clot formation after tissue injury. This then results in the formation of activated factor VII (VIIa)-tissue factor complexes, which must activate both factor X and factor...

  12. Magnetic particle imaging of blood coagulation

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-23

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

  13. Magnetic particle imaging of blood coagulation

    International Nuclear Information System (INIS)

    We investigated the feasibility of visualizing blood coagulation using a system for magnetic particle imaging (MPI). A magnetic field-free line is generated using two opposing neodymium magnets and transverse images are reconstructed from the third-harmonic signals received by a gradiometer coil, using the maximum likelihood-expectation maximization algorithm. Our MPI system was used to image the blood coagulation induced by adding CaCl2 to whole sheep blood mixed with magnetic nanoparticles (MNPs). The “MPI value” was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. MPI values were significantly smaller for coagulated blood samples than those without coagulation. We confirmed the rationale of these results by calculating the third-harmonic signals for the measured viscosities of samples, with an assumption that the magnetization and particle size distribution of MNPs obey the Langevin equation and log-normal distribution, respectively. We concluded that MPI can be useful for visualizing blood coagulation.

  14. New method for detection of blood coagulation using fiber-optic sensor

    Science.gov (United States)

    Fediay, Sergey G.; Kuznetzov, Alexsey V.

    1991-07-01

    The detection of blood coagulation is very important in therapeutics and surgery. It is necessary to determine the overall time taken for blood clotting, production rate of thrombin, presence or absence of blood coagulation factors, etc. In this paper a new method for detection of blood coagulation is presented. This method is based on the fiber-optic sensor and allows for the study of different ways of blood clotting (such as blood coagulation and platelets aggregation) separately, thus enhancing the precision of determination. The method for determining the blood coagulation presented possesses high precision in monitoring the process of coagulation. An elaborate mathematical model of the process of blood coagulation has been developed to help the computer handle obtained data.

  15. Radiation effects on blood coagulation

    International Nuclear Information System (INIS)

    Haemorrhage is an important and ominous sign in acute radiation disease. While it is overwhelmingly evident that thrombocytopenia is the major cause of the haemorrhagic diathesis, detailed observations of all of the changes in the coagulation mechanism, fibrinolytic elements and platelet function are lacking. The current knowledge is reviewed in this chapter. In general, changes should be considered in relation to the course of the disease, that is early or late, and whether the observations were made in man or animals

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

    International Nuclear Information System (INIS)

    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 (V120) despite the residual intrapulmonary clots after treatment in one examination. • The increased whole lung perfusion (V120) and a decreased low perfusion volume (V5) result in the improvement in the low perfusion rate (%V5) 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 (V120) and 1–5 HU (V5), and the relative value of V5 per V120 expressed as %V5. 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, V5 and %V5values 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 %V5 values were also significantly reduced, whereas the V5 value did not significantly decrease (p = 0.07), but V120 value significantly increased (p < 0.001) after treatment. However, in patients with IPCs the change rate in %V5 [(subsequent-initial)/initial %V5] showed a

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

    International Nuclear Information System (INIS)

    Factor XIII (plasma transglutaminase, fibrin stabilizing factor) is a glycoprotein that circulates in blood as a tetramer (a2b2) 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 ∼5 x 107 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

  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. 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; Sandstrom, B.

    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. Obj...

  1. 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

  2. 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.

  3. 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.

  4. Effects of Aerobic Fitness and Adiposity on Coagulation Biomarkers in Men vs. Women with Elevated Blood Pressure

    OpenAIRE

    Wilson, Kathleen L.; Lianne Tomfohr; Kate Edwards; Cindy Knott; Suzi Hong; Laura Redwine; Karen Calfas; Rock, Cheryl L.; Roland von Känel; Mills, Paul J.

    2012-01-01

    ABSTRACTA hypercoagulable state is a potential mechanism linking elevated blood pressure (BP), adiposity and a sedentary lifestyle to development of coronary heart disease (CHD). We examined relationships among aerobic fitness and adiposity in 76 sedentary subjects with elevated BP. Blood levels of plasminogen activator inhibitor-1 (PAI-1), D-dimer, von Willebrand factor (vWF) and thrombomodulin were assessed as biomarkers of coagulation. In individuals with elevated BP, percent body fat and ...

  5. Changes in Blood Parameters and Coagulation-Related Gene Expression in Pregnant Rats

    OpenAIRE

    Urasoko, Yoshinaka; He, Xi Jun; Ebata, Tomonori; KINOSHITA, YUICHI; Kobayashi, Junichi; Mochizuki, Masahiro; Ikeya, Masamichi

    2009-01-01

    The present study examined changes in maternal blood parameters, particularly those related to blood coagulation, as well as alterations in blood coagulation-related gene expression in the liver during gestation in rats. Fibrinogen concentration and platelet count increased as pregnancy progressed whereas prothrombin time and overall activity of vitamin-K–dependent coagulation factors decreased before delivery, suggesting a physiologic response to prevent prolonged bleeding at parturition. Co...

  6. 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.

  7. Blood viscosity during coagulation at different shear rates

    OpenAIRE

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

    2014-01-01

    Abstract During the coagulation process, blood changes from a liquid to a solid gel phase. These changes are reflected by changes in blood viscosity; however, blood viscosity at different shear rates (SR) has not been previously explored during the coagulation process. In this study, we investigated the viscosity changes of whole blood in 10 subjects with a normal coagulation profile, using a cone‐on‐plate viscosimeter. For each subject, three consecutive measurements were performed, at a SR ...

  8. Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange

    DEFF Research Database (Denmark)

    Rand, Kasper Dyrberg; Jørgensen, Thomas; Olsen, Ole H; Persson, Egon; Jensen, Ole; Stennicke, Henning R; Andersen, Mette

    2006-01-01

    Coagulation factor VIIa (FVIIa) is a serine protease that, after binding to tissue factor (TF), plays a pivotal role in the initiation of blood coagulation. We used hydrogen exchange monitored by mass spectrometry to visualize the details of FVIIa activation by comparing the exchange kinetics of ...... provide novel insights into the cofactor-induced activation of this important protease and reveal the potential for allosteric regulation in the trypsin family of proteases....

  9. 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.

  10. Systemic blood coagulation activation in acute coronary syndromes

    OpenAIRE

    Undas, Anetta; Szułdrzyński, Konstanty; Brummel-Ziedins, Kathleen E.; Tracz, Wiesława; Zmudka, Krzysztof; Mann, Kenneth G.

    2009-01-01

    We evaluated systemic alterations to the blood coagulation system that occur during a coronary thrombotic event. Peripheral blood coagulation in patients with acute coronary thrombosis was compared with that in people with stable coronary artery disease (CAD). Blood coagulation and platelet activation at the microvascular injury site were assessed using immunochemistry in 28 non-anticoagulated patients with acute myocardial infarction (AMI) versus 28 stable CAD patients matched for age, sex, ...

  11. Investigation of the possible link between exposure to air pollution and changes in blood coagulation parameters

    Energy Technology Data Exchange (ETDEWEB)

    Hazell, C.; Burr, M.; Collins, P.; Karani, G. [University of Wales, Cardiff (United Kingdom)

    1999-01-01

    The hypothesised relationship between variations in exposure to airborne pollution and changes in blood coagulation factors, as a causal factor in cardiovascular disease was investigated. The study was performed using two standard coagulation test results, compared to air pollution data, in the time period July 1996 to July 1997. Five air pollutants, PM{sub 10} NO{sub x}, SO{sub 2}, CO and O{sub 3} were correlated and compared with blood coagulation test results, to look for associations between exposure to air pollution and changes in blood coagulation factors. It was found that exposure to varying concentrations of air pollutants did not affect the blood coagulation times in the study group.

  12. 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....... Objective: We tested the hypothesis that FVII activation would be less after consumption of saturated fatty acids than after other fatty acids. Design: The effects of 6 matching dietary test fats, rich in stearic (S), palmitic (P), palmitic + myristic (M), oleic (O), trans 18:1 (T), and linoleic (L) acid......, respectively, on the postprandial lipid and hemostatic profile (after 2, 4, 6, and 8 h) were investigated in 16 young men. High-fat meals (1 g fat/kg body wt; 43% from the test fatty acid) were served in the morning on 6 separate days. Results: All fats increased FVII activation. The S fat resulted in a lower...

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples......-rich lipoproteins activate prokallikrein postprandially, which might form an important initial event in FVII activation after consumption of high-fat meals....... were collected. The high-fat test was associated with an increase in plasma triglyceride and kallikrein concentrations and postprandial FVII activation (p<0.001). Plasma kallikrein was strongly associated with triglycerides in fasting and non-fasting samples (r2=0.74-0.87, p<0.0001), suggesting that...

  14. Blood Coagulation Changes at High Altitude

    Directory of Open Access Journals (Sweden)

    I. S. Chohan

    1984-10-01

    Full Text Available The current concepts of blood coagulation changes in the pathogenesis of acute mountain sickness (AMS, high altitude pulmonary oedema (HAPO, high altitude pulmonary hypertension (HAPH and chronic mountain sickness(CMS which afflict the inductees and residents at high altitude have been reviewed. Hypercoagulable state which is more marked during the first few days of exposure is countered by enhanced fibrinolytic activity and accelerated cell mediated immunity. Magnesium levels are increased in normal residents at high altitudes and may be responsible for enhancing fibrinolytic activity and accelerating immune responses. Magnesium levels are significantly reduced in HAPO patients. Judicious use of furosemide in lower dosage is still the mainstay of treatment of HAPO and AMS.

  15. 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.

  16. Ranking reactive glutamines in the fibrinogen αC region that are targeted by blood coagulant factor XIII.

    Science.gov (United States)

    Mouapi, Kelly Njine; Bell, Jacob D; Smith, Kerrie A; Ariëns, Robert A S; Philippou, Helen; Maurer, Muriel C

    2016-05-01

    Factor XIIIa (FXIIIa) introduces covalent γ-glutamyl-ε-lysyl crosslinks into the blood clot network. These crosslinks involve both the γ and α chains of fibrin. The C-terminal portion of the fibrin α chain extends into the αC region (210-610). Crosslinks within this region help generate a stiffer clot, which is more resistant to fibrinolysis. Fibrinogen αC (233-425) contains a binding site for FXIIIa and three glutamines Q237, Q328, and Q366 that each participate in physiological crosslinking reactions. Although these glutamines were previously identified, their reactivities toward FXIIIa have not been ranked. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry and nuclear magnetic resonance (NMR) methods were thus used to directly characterize these three glutamines and probe for sources of FXIIIa substrate specificity. Glycine ethyl ester (GEE) and ammonium chloride served as replacements for lysine. Mass spectrometry and 2D heteronuclear single quantum coherence NMR revealed that Q237 is rapidly crosslinked first by FXIIIa followed by Q366 and Q328. Both (15)NH4Cl and (15)N-GEE could be crosslinked to the three glutamines in αC (233-425) with a similar order of reactivity as observed with the MALDI-TOF mass spectrometry assay. NMR studies using the single αC mutants Q237N, Q328N, and Q366N demonstrated that no glutamine is dependent on another to react first in the series. Moreover, the remaining two glutamines of each mutant were both still reactive. Further characterization of Q237, Q328, and Q366 is important because they are located in a fibrinogen region susceptible to physiological truncations and mutation. The current results suggest that these glutamines play distinct roles in fibrin crosslinking and clot architecture. PMID:26951791

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

    OpenAIRE

    van der Voort Danielle; Spronk Henri MH; ten Cate Hugo

    2004-01-01

    Abstract The principles of Virchov's triad appear to be operational in atherothrombosis or arterial thrombosis: local flow changes and particularly vacular wall damage are the main pathophysiological elements. Furthermore, alterations in arterial blood composition are also involved although the specific role and importance of blood coagulation is an ongoing matter of debate. In this review we provide support for the hypothesis that activated blood coagulation is an essential determinant of th...

  18. The use of recombinant activated coagulation factor VII for spine surgery

    OpenAIRE

    Weiskopf, Richard B.

    2004-01-01

    This article focuses on our current understanding of the role of activated coagulation factor VII (FVIIa) in coagulation, the current evidence regarding the efficacy and safety of recombinant FVIIa (rFVIIa), and thoughts regarding the use of rFVIIa in spine surgery. rFVIIa is approved in many countries (including the European Union and the USA) for patients with hemophilia and inhibitors (antibodies) to coagulation factors VIII or IX. High circulating concentrations of FVIIa, achieved by exog...

  19. Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro- 1H-pyrazolo[3,4-c]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Donald J.P.; Orwat, Michael J.; Koch, Stephanie; Rossi, Karen A.; Alexander, Richard S.; Smallwood, Angela; Wong, Pancras C.; Rendina, Alan R.; Luettgen, Joseph M.; Knabb, Robert M.; He, Kan; Xin, Baomin; Wexler, Ruth R.; Lam, Patrick Y.S. (BMS)

    2010-03-08

    Efforts to identify a suitable follow-on compound to razaxaban (compound 4) focused on modification of the carboxamido linker to eliminate potential in vivo hydrolysis to a primary aniline. Cyclization of the carboxamido linker to the novel bicyclic tetrahydropyrazolopyridinone scaffold retained the potent fXa binding activity. Exceptional potency of the series prompted an investigation of the neutral P{sub 1} moieties that resulted in the identification of the p-methoxyphenyl P{sub 1}, which retained factor Xa binding affinity and good oral bioavailability. Further optimization of the C-3 pyrazole position and replacement of the terminal P{sub 4} ring with a neutral heterocycle culminated in the discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, compound 40). Compound 40 exhibits a high degree of fXa potency, selectivity, and efficacy and has an improved pharmacokinetic profile relative to 4.

  20. 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.

  1. Using a Systems Pharmacology Model of the Blood Coagulation Network to Predict the Effects of Various Therapies on Biomarkers

    OpenAIRE

    S. Nayak; Lee, D.; Patel-Hett, S; Pittman, DD; Martin, SW; Heatherington, AC; Vicini, P.; F. Hua

    2015-01-01

    A number of therapeutics have been developed or are under development aiming to modulate the coagulation network to treat various diseases. We used a systems model to better understand the effect of modulating various components on blood coagulation. A computational model of the coagulation network was built to match in-house in vitro thrombin generation and activated Partial Thromboplastin Time (aPTT) data with various concentrations of recombinant factor VIIa (FVIIa) or factor Xa added to n...

  2. 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

  3. Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation

    OpenAIRE

    Kannemeier, Christian; Shibamiya, Aya; Nakazawa, Fumie; Trusheim, Heidi; Ruppert, Clemens; Markart, Philipp; Song, Yutong; Tzima, Eleni; Kennerknecht, Elisabeth; Niepmann, Michael; von Bruehl, Marie-Luise; Sedding, Daniel; Massberg, Steffen; Günther, Andreas; Engelmann, Bernd

    2007-01-01

    Upon vascular injury, locally controlled haemostasis prevents life-threatening blood loss and ensures wound healing. Intracellular material derived from damaged cells at these sites will become exposed to blood components and could contribute to blood coagulation and pathological thrombus formation. So far, the functional and mechanistic consequences of this concept are not understood. Here, we present in vivo and in vitro evidence that different forms of eukaryotic and prokaryotic RNA serve ...

  4. Sequential coagulation factor VIIa domain binding to tissue factor

    International Nuclear Information System (INIS)

    Vessel wall tissue factor (TF) is exposed to blood upon vascular damage which enables association with factor VIIa (FVIIa). This leads to initiation of the blood coagulation cascade through localization and allosteric induction of FVIIa procoagulant activity. To examine the docking pathway of the FVIIa-TF complex, various residues in the extracellular part of TF (sTF) that are known to interact with FVIIa were replaced with cysteines labelled with a fluorescent probe. By using stopped-flow fluorescence kinetic measurements in combination with surface plasmon resonance analysis, we studied the association of the resulting sTF variants with FVIIa. We found the docking trajectory to be a sequence of events in which the protease domain of FVIIa initiates contact with sTF. Thereafter, the two proteins are tethered via the first epidermal growth factor-like and finally the γ-carboxyglutamic acid (Gla) domain. The two labelled sTF residues interacting with the protease domain of FVIIa bind or become eventually ordered at different rates, revealing kinetic details pertinent to the allosteric activation of FVIIa by sTF. Moreover, when the Gla domain of FVIIa is removed the difference in the rate of association for the remaining domains is much more pronounced

  5. Blood coagulation using High Intensity Focused Ultrasound (HIFU)

    Science.gov (United States)

    Nguyen, Phuc V.; Oh, Junghwan; Kang, Hyun Wook

    2014-03-01

    High Intensity Focused Ultrasound (HIFU) technology provides a feasible method of achieving thermal coagulation during surgical procedures. One of the potential clinical benefits of HIFU can induce immediate hemostasis without suturing. The objective of this study was to investigate the efficiency of a HIFU system for blood coagulation on severe vascular injury. ngHIFU treatment was implemented immediately after bleeding in artery. The ultrasound probe was made of piezoelectric material, generating a central frequency of 2.0 MHz as well as an ellipsoidal focal spot of 2 mm in lateral dimension and 10 mm in axial dimension. Acoustic coagulation was employed on a perfused chicken artery model in vitro. A surgical incision (1 to 2 mm long) was made with a scapel on the arterial wall, and heparinized autologous blood was made to leak out from the incision with a syringe pump. A total of 5 femoral artery incisions was treated with the HIFU beam. The intensity of 4500 W/cm2 at the focus was applied for all treatments. Complete hemostasis was achieved in all treatments, along with the treatment times of 25 to 50 seconds. The estimated intraoperative blood loss was from 2 to 5 mL. The proposed HIFU system may provide an effective method for immediate blood coagulation for arteries and veins in clinical applications.

  6. 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.

  7. 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.

  8. Canine specific ELISA for coagulation factor VII

    DEFF Research Database (Denmark)

    Knudsen, Tom; Kjelgaard-Hansen, Mads; Tranholm, Mikael; Wiinberg, Bo; Clausen, Jes T.; Hansen, Jens Jacob; Nichols, Timothy C.; Kjalke, Marianne; Jensen, Asger Lundorff; Kristensen, Annemarie Thuri

    2011-01-01

    Canine coagulation factor VII (FVII) deficiency can be hereditary or acquired and may cause life threatening bleeding episodes if untreated. FVII procoagulant activity can be measured by FVII activity (FVII:C), but assays for measurement of canine specific FVII antigen (FVII:Ag) have not been...... available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable...... in the diagnosis of hereditary canine FVII deficiency....

  9. Acquired Factor V Inhibitor: A Case Report

    OpenAIRE

    Gaćina, Petar; Kušec, Rajko; Čaržavec, Dubravka; Raić, Biserka; Stančić, Vladimir

    2006-01-01

    A 19-year-old asymptomatic man who was admitted to our hospital for investigation of prolonged screening coagulation assays, prothrombin time and activated partial thromboplastin time is presented. Further evaluation revealed factor V deficiency and the presence of specific factor V inhibitors. The appearance of these inhibitors may be associated with administration of some antibiotics, topical bovine thrombin preparations containing bovine factor V during surgical or dental procedures, after...

  10. 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.

  11. Acquired Factor VIII Inhibitors: Three Cases

    Directory of Open Access Journals (Sweden)

    Tay Za Kyaw

    2013-03-01

    Full Text Available Acquired hemophilia A is a rare, but devastating bleeding disorder caused by spontaneous development of autoantibodies directed against coagulation factor VIII. In 40%-50% of patients it is associated with such conditions as the postpartum period, malignancy, use of medications, and autoimmune diseases; however, its cause is unknown in most cases. Acquired hemophilia A should be suspected in patients that present with a coagulation abnormality, and a negative personal and family history of bleeding. Herein we report 3 patients with acquired hemophilia A that had different underlying pathologies, clinical presentations, and therapeutic responses. Factor VIII inhibitor formation in case 1 occurred 6 months after giving birth; underlying disorders were not identified in cases 2 or 3. The bleeding phenotype in these patients’ ranged from no bleeding tendency with isolated prolongation of APTT (activated partial thromboplastin time to severe intramuscular hematoma and hemarthrosis necessitating recombinant activated factor VII infusion and blood components transfusion. Variable responses to immunosuppressive treatment were also observed.

  12. Changes in Blood Parameters and the Expression of Coagulation-Related Genes in Lactating Sprague–Dawley Rats

    OpenAIRE

    Urasoko, Yoshinaka; He, Xi Jun; Masao, Takano; KINOSHITA, YUICHI; Edamoto, Hiroshi; Hatayama, Kazuhisa; Asano, Yuzo; Tamura, Kazutoshi; Mochizuki, Masahiro

    2012-01-01

    This study measured blood parameters, particularly those related to coagulation, and alterations in the expression levels of blood-coagulation–related genes in lactating Sprague–Dawley rats. The day of delivery was designated as lactation day 0 (LD 0). On the day after delivery (LD 1), prothrombin time and overall activity of vitamin-K–dependent coagulation factors were decreased, whereas fibrinogen contents, platelet counts and antithrombin III concentrations were increased as compared with ...

  13. Coagulation factor therapy for hemophilia: relation to hepatitis B and to liver function.

    OpenAIRE

    Card, R. T.; Dusevic, M.; Lukie, B E

    1982-01-01

    Therapy with concentrated coagulation factors has greatly improved the management of hemophilia, but the consequence of repeated infusion of these blood products are unknown. Hepatic dysfunction is frequent in patients with hemophilia, and the use of these products may be responsible. The relation between liver function and both the frequency and type of therapy with coagulation factors was studied in a group of patients with hemophilia. Of the 36 patients studied, 75% were found to have anti...

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Cengiz Demir

    2010-01-01

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

  16. Phenyltriazolinones as potent factor Xa inhibitors.

    Science.gov (United States)

    Quan, Mimi L; Pinto, Donald J P; Rossi, Karen A; Sheriff, Steven; Alexander, Richard S; Amparo, Eugene; Kish, Kevin; Knabb, Robert M; Luettgen, Joseph M; Morin, Paul; Smallwood, Angela; Woerner, Francis J; Wexler, Ruth R

    2010-02-15

    We have discovered that phenyltriazolinone is a novel and potent P1 moiety for coagulation factor Xa. X-ray structures of the inhibitors with a phenyltriazolinone in the P1 position revealed that the side chain of Asp189 has reoriented resulting in a novel S1 binding pocket which is larger in size to accommodate the phenyltriazolinone P1 substrate. PMID:20100660

  17. 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

    Coagulated blood is a rich source of mRNA that allows the study of the regulation of expression of cytokine and other genes. However, while several methods are available for isolation of RNA from whole blood and tissues, protocols for purification of mRNA from clotted blood are not generally...

  18. 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

  19. Thrombin Activity Propagates in Space During Blood Coagulation as an Excitation Wave

    OpenAIRE

    Dashkevich, N.M.; Ovanesov, M.V.; Balandina, A.N.; Karamzin, S.S.; Shestakov, P.I.; Soshitova, N.P.; Tokarev, A.A.; Panteleev, M.A.; Ataullakhanov, F.I.

    2012-01-01

    Injury-induced bleeding is stopped by a hemostatic plug formation that is controlled by a complex nonlinear and spatially heterogeneous biochemical network of proteolytic enzymes called blood coagulation. We studied spatial dynamics of thrombin, the central enzyme of this network, by developing a fluorogenic substrate-based method for time- and space-resolved imaging of thrombin enzymatic activity. Clotting stimulation by immobilized tissue factor induced localized thrombin activity impulse t...

  20. The effect of administration of a single dose of T-2 toxin on blood coagulation in the rabbit.

    OpenAIRE

    Gentry, P A

    1982-01-01

    The single intravenous administration of T-2 toxin to rabbits at a dosage of 0.5 mg per kg body weight produced an alteration in several blood coagulation parameters. The activities of factors VII, VIII, IX, X and XI were decreased by approximately 40% six hours after T-2 toxin administration. Plasma fibrinogen concentration became elevated within 24 hours after T-2 toxin exposure. Circulating platelet numbers were unaffected by T-2 toxin administration. The similarity of coagulation paramete...

  1. Blood coagulation profiling in patients using optical thromboelastography (OTEG) (Conference Presentation)

    Science.gov (United States)

    Tripathi, Markandey M.; Tshikudi, Diane M.; Hajjarian, Zeinab; Van Cott, Elizabeth M.; Nadkarni, Seemantini K.

    2016-02-01

    Impaired blood coagulation is often associated with increased postoperative mortality and morbidity in cardiovascular patients. The capability for blood coagulation profiling rapidly at the bedside will enable the timely detection of coagulation defects and open the opportunity for tailoring therapy to correct specific coagulation deficits Optical Thromboelastography (OTEG), is an optical approach to quantify blood coagulation status within minutes using a few drops of whole blood. The goal of the current study is to evaluate the diagnostic accuracy of OTEG for rapid coagulation profiling in patients. In OTEG, temporal laser speckle intensity fluctuations from a drop of clotting blood are measured using a CMOS camera. To quantify coagulation status, the speckle intensity autocorrelation function is measured, the mean square displacement of scattering particles is extracted, and viscoelastic modulus (G), during coagulation is measured via the generalized Stokes-Einstein relation. By quantifying time-resolved changes in G, the coagulation parameters, reaction time (R), clot progression time (K), clot progression rate (Angle), and maximum clot strength (MA) are derived. In this study, the above coagulation parameters were measured using OTEG in 269 patients and compared with standard mechanical Thromboelastography (TEG). Our results showed a strong correlation between OTEG and TEG measurements for all parameters: R-time (R=0.80, pcoagulation status to potentially improve clinical capability for identifying impaired coagulation in cardiovascular patients at the point of care.

  2. Coagulation factors IX through XIII and the risk of future venous thrombosis: the Longitudinal Investigation of Thromboembolism Etiology

    OpenAIRE

    Cushman, Mary; O'Meara, Ellen S.; Folsom, Aaron R.; Heckbert, Susan R

    2009-01-01

    Higher levels of procoagulant factors and factor XII deficiency may be risk factors for first venous thromboembolism (VTE). We studied associations of coagulation factors IX through XIII with risk of future VTE in 2 general population samples. Using a nested case-control study combining the 21 860 participants of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study, we determined antigenic levels of these coagulation factors in primarily pre-event blood samples fr...

  3. 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

  4. 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.

  5. Inhibition of LPS-Induced Activation of Coagulation by p38 MAPK Inhibitor

    OpenAIRE

    Lutz Koch; Stefan Hofer; Weigand, Markus A.; David Frommhold; Johannes Poeschl; Peter Ruef

    2012-01-01

    During Gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like receptor (TLR) 4 and induces complex responses of immune system and coagulation. However, the underlying LPS signalling mechanism on coagulation activation remains complex. To determine the role of the intracellular signalling factors p38 mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF- κ B), and c-Jun N-terminal kinase (JNK) in the procoagulant response to LPS, coagulation process of human whole blo...

  6. Blood coagulation and fibrinolysis after long-duration treadmill exercise controlled by individual anaerobic threshold.

    Science.gov (United States)

    Hilberg, Thomas; Gläser, Doreen; Reckhart, Carsten; Prasa, Dagmar; Stürzebecher, Jörg; Gabriel, Holger H W

    2003-11-01

    For rehabilitation training it is recommended that the intensity of exercise should be clearly below the individual anaerobic threshold (IAT). We investigated blood coagulation, particularly endogenous thrombin potential (ETP) and fibrinolysis following a standardized treadmill (TR) ergometer test at 90% IAT for 60-120 min. Sixteen healthy male non-smokers underwent the TR test. Blood samples were taken after a 30-min rest, immediately after exercise, and 2 h after exercise completion. Extrinsic and intrinsic total (TTP(ex+in)) and endogenous (ETP(ex+in)) thrombin potential, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), plasmin-alpha2-antiplasmin complex (PAP), D-dimer, tissue plasminogen activator antigen and activity (tPA-AG and tPA-ACT) and plasminogen activator inhibitor type 1 antigen and activity (PAI-1-AG and PAI-1-ACT) were measured. Immediately after TR, F1+2, TAT and TTP(ex+in) were increased ( PIAT (90%) on a TR ergometer only implicates a small increase in thrombin generation markers and total (free and alpha(2)-macroglubulin-bound thrombin), but not in endogenous (free) thrombin potential alone. In contrast, fibrinolysis is distinctly increased after this type of exercise. Endurance exercise with an intensity below 90% IAT and a duration below 2 h generates a more favourable condition for fibrinolysis than for blood coagulation in healthy young subjects. Data are given as mean (SD). PMID:12883904

  7. 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.

  8. 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.

  9. 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.

  10. Effects of storage time and temperature on coagulation tests and factors in fresh plasma

    OpenAIRE

    Limin Feng; Ying Zhao; Hongcan Zhao; Zhexin Shao

    2014-01-01

    Coagulation tests and factors measurements have been widely applied in clinical practice. Pre-analytical conditions are very important in laboratory assessment.Here,we aim to determine the effects of storage time and temperature on activated partial thromboplastin time (APTT), fibrinogen (Fbg), prothrombin time (PT), the international normalized ratio (INR), thrombin time (TT), factor VIII activity (FVIII:C), and factor IX activity (FIX:C) in fresh plasma. Seventy-two blood samples were teste...

  11. 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...

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

    OpenAIRE

    Andersen, Nina Marianne; Sørensen, Mads Peter; Messoud A. Efendiev; Olsen, Ole Hvilsted; Ingwersen, Steen H.

    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 account the spatial distribution of the biochemical species. An important issue is inclusion of a dynamic boundary condition describing adhesion of activated platelets on a collagen coated top lid in...

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

    Directory of Open Access Journals (Sweden)

    A. A. Arshinov

    2005-04-01

    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.

  14. Effect of onion and garlic on blood coagulation and fibrinolysis in vitro.

    Science.gov (United States)

    Nagda, K K; Ganeriwal, S K; Nagda, K C; Diwan, A M

    1983-01-01

    The effects of aqueous extracts of onion and garlic as well as of garlic oil were studied on the process of blood coagulation and fibrinolysis in vitro. Only onion was found to exhibit anti-coagulant and fibrinolytic activity while garlic extract as well as garlic oil were inactive. PMID:6885127

  15. Effect of catheter flush fluids on blood coagulation and aggregation of platelets

    International Nuclear Information System (INIS)

    The effect upon blood coagulation and aggregation of platelets of a polysaccharide catheter flush fluid (flush fluid E) was investigated and compared with isotonic saline and Isopaque Cerebral. The result indicates that flush fluid E does not activate the coagulation system. (Auth.)

  16. Development of coagulation factor probes for the identification of procoagulant circulating tumor cells

    Directory of Open Access Journals (Sweden)

    GarthWilliamTormoen

    2012-09-01

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

  17. 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

  18. Real-Time Electrical Impedimetric Monitoring of Blood Coagulation Process under Temperature and Hematocrit Variations Conducted in a Microfluidic Chip

    OpenAIRE

    Lei, Kin Fong; Chen, Kuan-Hao; Tsui, Po-Hsiang; Tsang, Ngan-Ming

    2013-01-01

    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 sa...

  19. 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.

  20. 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...

  1. 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...

  2. 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...

  3. 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)

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

    Science.gov (United States)

    Xu, Xiangqun; Teng, Xiangshuai

    2015-05-01

    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.

  5. Perturbed blood coagulation and fibrinolysis in rabbits after irradiation to the liver

    International Nuclear Information System (INIS)

    Effects of X-ray irradiation to the liver were studied in rabbits with special reference to the free radicals induced by the irradiation at various doses of 5, 10, 20 and 40 Gy. Results were summarized as follows: (1) APTT and PT significantly prolonged immediately after irradiation and on day 1, and recovered thereafter to the control levels. (2) Levels of blood coagulation factors I, II and plasminogen, t-PA and plasma prekallikrein showed similar trends, namely, an initial rapid decrease immediately after irradiation, followed by a transient increase on day 3 and a subsequent recovery to the control level on days 7 and 10. These changes coincided with the prolongation of ATPP and PT. (3) The SOD activity and the plasma albumin level also decreased immediately after irradiation, recovered once from 3 to 7 days and decreased again on days 10. The decreased SOD activity noted immediately after irradiation indicates production of free radicals induced by the irradiation. This finding may suggest that the free radicals thus produced may have perturbed blood coagulation and fibrinolysis, at least in part, by blocking the secretion of relevant proteins from the hepatocytes. (author)

  6. Tissue regenerating functions of coagulation factor XIII

    DEFF Research Database (Denmark)

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

    2013-01-01

    The protransglutaminase factor XIII (FXIII) has recently gained interest within the field of tissue regeneration, as it has been found that FXIII significantly influences wound healing by exerting a multitude of functions. It supports haemostasis by enhancing platelet adhesion to damaged endothel......The protransglutaminase factor XIII (FXIII) has recently gained interest within the field of tissue regeneration, as it has been found that FXIII significantly influences wound healing by exerting a multitude of functions. It supports haemostasis by enhancing platelet adhesion to damaged...... endothelium, and by its cross-linking activity it stabilizes the formed fibrin clot. Furthermore, FXIII limits bacterial dissemination from the wound and incorporates macromolecules of importance for cellular infiltration supporting cell migration and survival. FXIII-mediated complex formation of the VEGF...

  7. 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

  8. 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.

  9. 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.

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

    Science.gov (United States)

    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 factor-factor VIIa. PMID:12738659

  11. 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

  12. Blood coagulation screening using a paper-based microfluidic lateral flow device.

    Science.gov (United States)

    Li, H; Han, D; Pauletti, G M; Steckl, A J

    2014-10-21

    A simple approach to the evaluation of blood coagulation using a microfluidic paper-based lateral flow assay (LFA) device for point-of-care (POC) and self-monitoring screening is reported. The device utilizes whole blood, without the need for prior separation of plasma from red blood cells (RBC). Experiments were performed using animal (rabbit) blood treated with trisodium citrate to prevent coagulation. CaCl2 solutions of varying concentrations are added to citrated blood, producing Ca(2+) ions to re-establish the coagulation cascade and mimic different blood coagulation abilities in vitro. Blood samples are dispensed into a paper-based LFA device consisting of sample pad, analytical membrane and wicking pad. The porous nature of the cellulose membrane separates the aqueous plasma component from the large blood cells. Since the viscosity of blood changes with its coagulation ability, the distance RBCs travel in the membrane in a given time can be related to the blood clotting time. The distance of the RBC front is found to decrease linearly with increasing CaCl2 concentration, with a travel rate decreasing from 3.25 mm min(-1) for no added CaCl2 to 2.2 mm min(-1) for 500 mM solution. Compared to conventional plasma clotting analyzers, the LFA device is much simpler and it provides a significantly larger linear range of measurement. Using the red colour of RBCs as a visible marker, this approach can be utilized to produce a simple and clear indicator of whether the blood condition is within the appropriate range for the patient's condition. PMID:25144164

  13. 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.

  14. Sequence-specific 1H NMR assignments, secondary structure, and location of the calcium binding site in the first epidermal growth factor like domain of blood coagulation factor IX

    International Nuclear Information System (INIS)

    Factor IX is a blood clotting protein that contains three regions, including a γ-carboxyglutamic acid (Gla) domain, two tandemly connected epidermal growth factor like (EGF-like) domains, and a serine protease region. The protein exhibits a high-affinity calcium binding site in the first EGF0like domain, in addition to calcium binding in the Gla domain. The first EGF-like domain, factor IX (45-87), has been synthesized. Sequence-specific resonance assignment of the peptide has been made by using 2D NMR techniques, and its secondary structure has been determined. The protein is found to have two antiparallel β-sheets, and preliminary distance geometry calculations indicate that the protein has two domains, separated by Trp28, with the overall structure being similar to that of EGF. An NMR investigation of the calcium-bound first EGF-like domain indicates the presence and location of a calcium binding site involving residues on both strands of one of the β-sheets as well as the N-terminal region of the peptide. These results suggest that calcium binding in the first EGF-like domain could induce long-range (possibly interdomain) conformational changes in factor IX, rather than causing structural alterations in the EGF-like domain itself

  15. 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.

  16. 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

  17. Ir-CPI, a coagulation contact phase inhibitor from the tick Ixodes ricinus, inhibits thrombus formation without impairing hemostasis

    OpenAIRE

    Decrem, Yves; Rath, Géraldine; Blasioli, Virginie; Cauchie, Philippe; Robert, Severine; Beaufays, Jerome; Frere, Jean-Marie; Feron, Olivier; Dogne, Jean-Michel; Dessy, Chantal; Vanhamme, Luc; Godfroid, Edmond

    2009-01-01

    Blood coagulation starts immediately after damage to the vascular endothelium. This system is essential for minimizing blood loss from an injured blood vessel but also contributes to vascular thrombosis. Although it has long been thought that the intrinsic coagulation pathway is not important for clotting in vivo, recent data obtained with genetically altered mice indicate that contact phase proteins seem to be essential for thrombus formation. We show that recombinant Ixodes ricinus contact ...

  18. 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; Jespersen, J

    2007-01-01

    BACKGROUND: Hormone therapy (HT) after the menopause is associated with increased risk of venous thromboembolism (VTE). Tibolone has pharmacodynamic properties different from other hormone preparations. We compared the effect of a combined HT and tibolone on the inhibition of haemostasis. METHODS......: 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...... (P = 0.002), protein S (P < 0.001) and TFPI (P < 0.001). Both preparations reduced the concentration of plasminogen activator inhibitor 1 (P < 0.05). CONCLUSIONS: Tibolone induces fewer pharmacological alterations on blood coagulability than CEE/MPA and has a potentially favourable effect on APC...

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

    International Nuclear Information System (INIS)

    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 show that coagulation factor (F)Xa drives tumor cells of epithelial origin, but not endothelial cells or monocytes, into apoptosis, whereas it even enhances fibroblast survival. FXa signals through the protease activated receptor (PAR)-1 to activate extracellular-signal regulated kinase (ERK) 1/2 and p38. This activation is associated with phosphorylation of the transcription factor CREB, and in tumor cells with up-regulation of the BH3-only pro-apoptotic protein Bim, leading to caspase-3 cleavage, the main hallmark of apoptosis. Transfection of tumor cells with dominant negative forms of CREB or siRNA for either PAR-1, Bim, ERK1 and/or p38 inhibited the pro-apoptotic effect of FXa. In fibroblasts, FXa-induced PAR-1 activation leads to down-regulation of Bim and pre-treatment with PAR-1 or Bim siRNA abolishes proliferation. We thus provide evidence that beyond its role in blood coagulation, FXa plays a key role in cellular processes in which Bim is the central player in determining cell survival

  20. EFFECT OF CONCENTRATED AMBIENT PARTICULATE MATTER ON BLOOD COAGULATION PARAMETERS IN RATS

    Science.gov (United States)

    Dr. Nadziejko and her colleagues at the New York University School of Medicine plan to evaluate the effects of exposing healthy rats to concentrated ambient particles (CAPs) and changes in blood coagulation parameters. The investigators expect to measure platelet number, bl...

  1. 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...

  2. 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...

  3. 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.

  4. 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

  5. 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...

  6. Coagulation Factor X Activates Innate Immunity to Human Species C Adenovirus

    OpenAIRE

    Doronin, Konstantin; Flatt, Justin W.; Di Paolo, Nelson C; Khare, Reeti; Kalyuzhniy, Oleksandr; Acchione, Mauro; Sumida, John P.; Ohto, Umeharu; Shimizu, Toshiyuki; Akashi-Takamura, Sachiko; Miyake, Kensuke; MacDonald, James W.; Bammler, Theo K.; Beyer, Richard P.; Farin, Frederico M

    2012-01-01

    Although coagulation factors play a role in host defense for “living fossils” such as horseshoe crabs, the role of the coagulation system in immunity in higher organisms remains unclear. We modeled the interface of human species C adenovirus (HAdv) interaction with coagulation factor X (FX) and introduced a mutation that abrogated formation of the HAdv-FX complex. In vivo genome-wide transcriptional profiling revealed that FX-binding–ablated virus failed to activate a distinct network of nucl...

  7. 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

  8. 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...

  9. [Status of blood coagulation and various background endocrine indices in patients with basal meningiomas during pre- and postoperative periods].

    Science.gov (United States)

    Burgman, G P; Snigireva, R Ia; Vial'tseva, I N; Shvorneva, V Z; Snigirev, V S

    1980-01-01

    The condition of blood coagulation activity and the indices of the endocrine background were studied in patients with tumors of prevalently basal localization which caused a direct effect on the central regulating centers. Thirty patients with basal and medially located meningiomas were examined in the pre- and postoperative periods. Before the operation most patients had clinical signs of endocrine-metabolic disorders, often in the presence of an increased content of ACTH and cortisol in the blood. Blood coagulation was disturbed in the majority of patients, mainly due to increased activity of the blood coagulation system. In the postoperative period, blood coagulation activity in 24 of 30 patients was increased or showed a tendency to increase in the presence of elevated blood ACTH content while processes of fibrinolysis were inhibited, which substantiates the necessity for anticoagulant therapy when large doses of glucocorticoids are used. PMID:6254292

  10. 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.

  11. 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 ...

  12. 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

  13. 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.

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

    Science.gov (United States)

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

    2016-04-01

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

  15. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Blood coagulation and platelet adhesion on polyaniline films

    Czech Academy of Sciences Publication Activity Database

    Humpolíček, P.; Kuceková, Z.; Kašpárková, V.; Pelková, J.; Modic, M.; Junkar, I.; Trchová, Miroslava; Bober, Patrycja; Stejskal, Jaroslav; Lehocký, M.

    2015-01-01

    Roč. 133, 1 September (2015), s. 278-285. ISSN 0927-7765 R&D Projects: GA ČR(CZ) GA13-08944S Institutional support: RVO:61389013 Keywords : polyaniline * poly(2-acrylamido-2-methyl-1-propanesulfonic acid) * hemocompatibility Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.152, year: 2014

  18. Multiple presence of prothrombotic risk factors in Croatian children with arterial ischemic stroke and transient ischemic attack

    OpenAIRE

    Leniček Krleža, Jasna; Đuranović, Vlasta; Bronić, Ana; Coen Herak, Desiree; Mejaški-Bošnjak, Vlatka; Zadro, Renata

    2013-01-01

    Aim To determine the frequency of inherited and acquired prothrombotic risk factors in children with arterial ischemic stroke (AIS) and transient ischemic attacks (TIA) in Croatia. Methods We investigated 14 prothrombotic risk factors using blood samples from 124 children with AIS or TIA and 42 healthy children. Prothrombotic risk factors were classified into five groups: natural coagulation inhibitors (antithrombin, protein C, protein S), blood coagulation factors (FV Leiden and FII 20210), ...

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

    Science.gov (United States)

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

    2016-05-01

    Coagulopathies following snakebite are triggered by pro-coagulant venom toxins, in which metalloproteases play a major role in envenomation-induced coagulation disorders by acting on coagulation cascade, platelet function and fibrinolysis. Considering this relevance, here we describe the isolation and biochemical characterization of moojenactivase (MooA), a metalloprotease from Bothrops moojeni snake venom, and investigate its involvement in hemostasis in vitro. MooA is a glycoprotein of 85,746.22 Da, member of the PIIId group of snake venom metalloproteases, composed of three linked disulfide-bonded chains: an N-glycosylated heavy chain, and two light chains. The venom protease induced human plasma clotting in vitro by activating on both blood coagulation factors II (prothrombin) and X, which in turn generated α-thrombin and factor Xa, respectively. Additionally, MooA induced expression of tissue factor (TF) on the membrane surface of peripheral blood mononuclear cells (PBMC), which led these cells to adopt pro-coagulant characteristics. MooA was also shown to be involved with production of the inflammatory mediators TNF-α, IL-8 and MCP-1, suggesting an association between MooA pro-inflammatory stimulation of PBMC and TF up-regulation. We also observed aggregation of washed platelets when in presence of MooA; however, the protease had no effect on fibrinolysis. Our findings show that MooA is a novel hemostatically active metalloprotease, which may lead to the development of coagulopathies during B. moojeni envenomation. Moreover, the metalloprotease may contribute to the development of new diagnostic tools and pharmacological approaches applied to hemostatic disorders. PMID:26026608

  20. [Evaluation of the blood coagulation system after surgeries on abdominal aortic aneurysms].

    Science.gov (United States)

    Nikul'nikov, P I; Liksunov, O V; Ratushniuk, A V; Lugovs'koĭ, E V; Kolesnikova, I M; Lytvynova, L M; Kostiuchenko, O P; Chernyshenko, T M; Hornyts'ka, O V; Platonova, T M

    2012-09-01

    Basing on data of analysis of the hemostasis system state in the patients, suffering abdominal aorta aneurysm, a tendency for raising of postoperative soluble fibrin and D-dimer content in the blood plasm and reduction of these indices on the third day was noted. The abovementioned markers content depends on the aneurysm size, the fibrin deposits presence, the terms from clinical signs beginning to the certain therapy administration and anticoagulants application. Information about correlation between content of D-dimer and soluble fibrin in the treatment dynamics is important for determination of activation degree in the patients blood coagulation system and the thrombotic complications prognosis. PMID:23285650

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

    DEFF Research Database (Denmark)

    Sun, Wei; Parry, Simon; Ubhayasekera, Wimal;

    2010-01-01

    . Furthermore, we have provided experimental evidence that PCI in both individuals is O-glycosylated on Thr20 with a core type 1 O-glycan, which is mostly NeuAcGalGalNAc. Modeling suggested that the O-glycan attachment site is located in proximity to several ligand-binding sites of the inhibitor.......Protein C inhibitor (PCI) is a 57-kDa glycoprotein that exists in many tissues and secretions in human. As a member of the serpin superfamily of proteins it displays unusually broad protease specificity. PCI is implicated in the regulation of a wide range of processes, including blood coagulation...

  2. Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III.

    Science.gov (United States)

    Cichon, Sven; Martin, Ludovic; Hennies, Hans Christian; Müller, Felicitas; Van Driessche, Karen; Karpushova, Anna; Stevens, Wim; Colombo, Roberto; Renné, Thomas; Drouet, Christian; Bork, Konrad; Nöthen, Markus M

    2006-12-01

    Hereditary angioedema (HAE) is characterized clinically by recurrent acute skin swelling, abdominal pain, and potentially life-threatening laryngeal edema. Three forms of HAE have been described. The classic forms, HAE types I and II, occur as a consequence of mutations in the C1-inhibitor gene. In contrast to HAE types I and II, HAE type III has been observed exclusively in women, where it appears to be correlated with conditions of high estrogen levels--for example, pregnancy or the use of oral contraceptives. A recent report proposed two missense mutations (c.1032C-->A and c.1032C-->G) in F12, the gene encoding human coagulation factor XII (FXII, or Hageman factor) as a possible cause of HAE type III. Here, we report the occurrence of the c.1032C-->A (p.Thr328Lys) mutation in an HAE type III-affected family of French origin. Investigation of the F12 gene in a large German family did not reveal a coding mutation. Haplotype analysis with use of microsatellite markers is compatible with locus heterogeneity in HAE type III. To shed more light on the pathogenic relevance of the HAE type III-associated p.Thr328Lys mutation, we compared FXII activity and plasma levels in patients carrying the mutation with that of healthy control individuals. Our data strongly suggest that p.Thr328Lys is a gain-of-function mutation that markedly increases FXII amidolytic activity but that does not alter FXII plasma levels. We conclude that enhanced FXII enzymatic plasma activity in female mutation carriers leads to enhanced kinin production, which results in angioedema. Transcription of F12 is positively regulated by estrogens, which may explain why only women are affected with HAE type III. The results of our study represent an important step toward an understanding of the molecular processes involved in HAE type III and provide diagnostic and possibly new therapeutic opportunities. PMID:17186468

  3. Ochratoxin A inhibits the production of tissue factor and plasminogen activator inhibitor-2 by human blood mononuclear cells: Another potential mechanism of immune-suppression

    International Nuclear Information System (INIS)

    The mycotoxin ochratoxin A (OTA), an ubiquitous contaminant of food products endowed with a wide spectrum of toxicity, affects several functions of mononuclear leukocytes. Monocytes/macrophages play a major role in fibrin accumulation associated with immune-inflammatory processes through the production of tissue factor (TF) and plasminogen activator inhibitor 2 (PAI-2). We studied the effect of OTA on TF and PAI-2 production by human blood mononuclear cells (MNC). The cells were incubated for 3 or 18 h at 37 deg. C with non toxic OTA concentrations in the absence and in the presence of lipopolysaccharide (LPS) or other inflammatory agents. TF activity was measured by a one-stage clotting test. Antigen assays were performed by specific ELISAs in cell extracts or conditioned media and specific mRNAs were assessed by RT-PCR. OTA had no direct effect on TF and PAI-2 production by MNC. However, OTA caused a dose-dependent reduction in LPS-induced TF (activity, antigen and mRNA) and PAI-2 (antigen and mRNA) production with > 85% inhibition at 1 μg/ml. Similar results were obtained when monocyte-enriched preparations were used instead of MNC. TF production was also impaired by OTA (1 μg/ml) when MNC were stimulated with phorbol myristate acetate (98% inhibition), IL-1β (83%) or TNF-α (62%). The inhibition of TF and PAI-2 induction might represent a hitherto unrecognized mechanism whereby OTA exerts immunosuppressant activity

  4. 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 ...

  5. Acquired factor V inhibitors in a polytraumatized patient

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    Tukić Ljiljana

    2005-01-01

    Full Text Available Background. Factor V (FV inhibitors are a rare disorder reported for the first time about fifty years ago, mostly with the unknown cause. The appearance of FV inhibitors is usually preceded by surgery, infections, administration of antibiotics or transfusions. Clinical manifestations of the presence of FV inhibitors vary from mild to severe and in some instances fatal hemorrhage. Case report. A healthy 51-year-old man with severe multiple injuries (traffic accident, and hemorrhage, which occurred during the orthopedic treatment, was admitted with hemoptysis, epistaxis and hematoma of the right upper leg, and with prolonged prothrombin time (PT, and activated partial thromboplastin time (aPTT. Treatment with vitamin K, fresh-frozen plasma and cryoprecipitate stopped the hemorrhage, but the results of coagulation tests were not normalized. The correction of aPTT and PT with normal plasma showed the decreased activity of FV (1% due to the presence of inhibitors (titer 17.5 IU. The abnormal results of coagulation tests remained for three weeks, but without clinically manifested hemorrhagic syndrome. At the fourth week after the appearance of FV inhibitors PT, aPTT and the activity of FV became normal and antibodies disappeared spontaneously. Conclusion. Our patient with polytrauma developed a mild hemorrhagic syndrome due to the presence of FV inhibitors five weeks after the accident. Hemorrhage was treated with substitution therapy. The cause of the development of FV inhibitors was unclear (“fibrin glue” was not used during the orthopedic treatment. Factor V inhibitors disappeared spontaneously within four weeks. The fast spontaneous disappearance of FV inhibitors in our patient, confirmed the observations of some authors that they disappeared faster in those patients who were surgically treated prior to their appearance.

  6. Changes in Dietary Fat Content Rapidly Alters the Mouse Plasma Coagulation Profile without Affecting Relative Transcript Levels of Coagulation Factors

    Science.gov (United States)

    van Diepen, Janna A.; Verhoef, Daniël; Voshol, Peter J.; Reitsma, Pieter H.; van Vlijmen, Bart J. M.

    2015-01-01

    Background Obesity is associated with a hypercoagulable state and increased risk for thrombotic cardiovascular events. Objective Establish the onset and reversibility of the hypercoagulable state during the development and regression of nutritionally-induced obesity in mice, and its relation to transcriptional changes and clearance rates of coagulation factors as well as its relation to changes in metabolic and inflammatory parameters. Methods Male C57BL/6J mice were fed a low fat (10% kcal as fat; LFD) or high fat diet (45% kcal as fat; HFD) for 2, 4, 8 or 16 weeks. To study the effects of weight loss, mice were fed the HFD for 16 weeks and switched to the LFD for 1, 2 or 4 weeks. For each time point analyses of plasma and hepatic mRNA levels of coagulation factors were performed after overnight fasting, as well as measurements of circulating metabolic and inflammatory parameters. Furthermore, in vivo clearance rates of human factor (F) VII, FVIII and FIX proteins were determined after 2 weeks of HFD-feeding. Results HFD feeding gradually increased the body and liver weight, which was accompanied by a significant increase in plasma glucose levels from 8 weeks onwards, while insulin levels were affected after 16 weeks. Besides a transient rise in cytokine levels at 2 weeks after starting the HFD, no significant effect on inflammation markers was present. Increased plasma levels of fibrinogen, FII, FVII, FVIII, FIX, FXI and FXII were observed in mice on a HFD for 2 weeks, which in general persisted throughout the 16 weeks of HFD-feeding. Interestingly, with the exception of FXI the effects on plasma coagulation levels were not paralleled by changes in relative transcript levels in the liver, nor by decreased clearance rates. Switching from HFD to LFD reversed the HFD-induced procoagulant shift in plasma, again not coinciding with transcriptional modulation. Conclusions Changes in dietary fat content rapidly alter the mouse plasma coagulation profile, thereby

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

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    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.

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

    Directory of Open Access Journals (Sweden)

    Zhi-Qiang Cui

    2015-01-01

    Full Text Available 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 ± 0.11, 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.

  9. 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

  10. 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.

  11. [State of the blood coagulation in glial tumors of the brain].

    Science.gov (United States)

    Burgman, G P; Kachkov, I A; Vial'tseva, I N; Shcherbakova, G G

    1979-01-01

    The data presented may be of definite value in the prevention of hemorrhage and thrombosis in patients with malignant glial tumors. A malignant glioma may lead to increased activity of the blood coagulation system (BCS). Preoperative staining of the tumor was not attended by marked changes in the BCS and blood viscocity, though a tendency towards an increase in BCS activity according to some of the indices may sometimes be noted. Chemotherapy with nitrosourea and methotrexate was attended by thrombocytopenia but there was practically no changes in the other BCS indices. The postoperative period is usually marked by increased BCS activity according to most of the indices. Increased blood viscocity is often encountered in patients with glial cerebral tumors in the preoperative and postoperative periods, which is evidently due to the intensive dehydration therapy to which they are subjected in marked increase of intracranial pressure. PMID:223352

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  14. 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, ac...

  15. Different Types of the Coagulation Disorders in Hamadan and A Comparison of the ABO & Rh Blood Group Distribution in the Patients and the Control Group

    Directory of Open Access Journals (Sweden)

    H. Pour-Jafari

    2003-10-01

    Full Text Available Patients with hemophilia and thalassemia are two groups of hereditary disorders that, periodically, use blood and blood substances. The aims of the present study are determination of the frequencies of different types of coagulation disorders, and a comparison of the frequencies of ABO & Rh phenotypes among affected individuals with the control group (blood donors. The subject group were all affected persons were referred to hemophilia and thalassemia centers in Hamadan. Primary information was collected from their files, then were classified and analyzed. The control group were blood donors that were registered in Hamadan blood bank. Results showed that the different types of coagulation disorders in affected individuals referred to the Hemophilia and thalassemia centers during 1998 were Hemophilia A (61.96%, Hemophilia B (20.86%, Von Willbrand (5.52%, Platelet deficiency (4.91%, Factor XIII deficiency (3.68% and Factor VII deficiency (3.07%. In general, results showed that in population with Hemophilia A, frequencies of A and O blood types were statistically different with the blood donors. The lowest rate of negative Rh, was in the population with thalassemia. The sex ratio of the affected persons was also different with control group.

  16. 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

  17. 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.

  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

    International Nuclear Information System (INIS)

    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

    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)

  1. 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.

  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. Human tissue factor pathway inhibitor (TFPI) gene: Complete genomic structure and localization on the genetic map of chromosome 2q

    Energy Technology Data Exchange (ETDEWEB)

    Enjyoji, Kei-ichi; Emi, Mitsuru; Mukai, Tsunehiro; Imada, Motohiro; Kato, Hisao (National Cardiovascular Center, Osaka (Japan)); Leppert, M.L.; Lalouel, J.M. (Howard Hughes Medical Institute, Salt Lake City, UT (United States) Univ. of Utah Medical School, Salt Lake City, UT (United States))

    1993-08-01

    Tissue factor pathway inhibitor (TFPI), a protease inhibitor that circulates in association with plasma lipoproteins (VLDL, LDL and HDL), helps to regulate the extrinsic blood coagulation cascade. The authors have cloned a 125-kb genomic region containing the entire human TFPI gene on six overlapping cosmids and prepared a restriction map of this contig to clarify gene structure. More than half (45 kb) of the 85-kb gene is occupied with 5[prime] noncoding elements: coding begins at exon 3. A HindIII RFLP identified with one cosmid was genotyped in the CEPH panel of 559 reference families. Linkage analysis using markers on human chromosome 2 located the TFPI gene on 2q, 36 cM proximal to D2S43(pYNZ15) and 13 cM distal to the crystalline [gamma]-polypeptide locus CRYGP1(p5G1). 31 refs., 3 figs., 3 tabs.

  4. Effects of radiation therapy on blood coagulation-fibrinolysis system in patients with oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    The aims of this study were to clarify the effects of radiotherapy on haemostatic activity in patients with oral squamous cell carcinoma (SCC) and to investigate the differences in the clinical findings. The subjects were 61 patients with primary oral SCC (SCC group) who had undergone preoperative radiotherapy of 34.2±7.2 Gy (mean±SD). These patients were divided into early group (stage I and II) and advanced group (stage III and IV), and the region in the oral cavity. Before and after radiotherapy, activated partial thromboplastin time (APTT), fibrinogen, prothrombin fragment 1+2 (F1+2) and plasmin-α2 plasmin inhibitor complex (PAP) were measured. In SCC group, after the radiotherapy, APTT extended and PAP increased. In the early stage group, PAP increased and in the advanced group, there was the extension of APTT. The regional division of the patients, there was the extension of APTT in oral floor and lower gingiva groups. F1+2 in lower gingiva group increased, and PAP rose in tongue and buccal mucosa groups. These results indicate that irradiation affects blood coagulation fibrinolysis system in patients with oral SCC, but the amount of the activation differs by the clinical findings. (author)

  5. 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

  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. Structural and functional influences of coagulation factor XIII subunit B heterozygous missense mutants.

    Science.gov (United States)

    Thomas, Anne; Biswas, Arijit; Ivaskevicius, Vytautas; Oldenburg, Johannes

    2015-07-01

    The coagulation factor XIII(FXIII) is a plasma circulating heterotetrameric protransglutaminase that acts at the end of the coagulation cascade by covalently cross-linking preformed fibrin clots (to themselves and to fibrinolytic inhibitors) in order to stabilize them against fibrinolysis. It circulates in the plasma as a heterotetramer composed of two homomeric catalytic Factor XIIIA2 (FXIIIA2) and two homomeric protective/carrier Factor XIIIB2 subunit (FXIIIB2). Congenital deficiency of FXIII is of two types: severe homozygous/compound heterozygous FXIII deficiency which results in severe bleeding symptoms and mild heterozygous FXIII deficiency which is associated with mild bleeding (only upon trauma) or an asymptomatic phenotype. Defects in the F13B gene (Factor XIIIB subunit) occur more frequently in mild FXIII deficiency patients than in severe FXIII deficiency. We had recently reported secretion-related defects for seven previously reported F13B missense mutations. In the present study we further analyze the underlying molecular pathological mechanisms as well as the heterozygous expression phenotype for these mutations using a combination of in vitro heterologous expression (in HEK293T cells) and confocal microscopy. In combination with the in vitro work we have also performed an in silico solvated molecular dynamic simulation study on previously reported FXIIIB subunit sushi domain homology models in order to predict the putative structure-functional impact of these mutations. We were able to categorize the mutations into the following functional groups that: (1) affect antigenic stability as well as binding to FXIIIA subunit, that is, Cys5Arg, Cys316Phe, and Pro428Ser (2) affect binding to FXIIIA subunit with little or no influence on antigenic stability, that is, Ile81Asn and Val401Gln c) influence neither aspects and are most likely causality linked polymorphisms or functional polymorphisms, that is, Leu116Phe and Val217Ile. The Cys5Arg mutation was the

  8. Short-term Effects of Air Temperature on Blood Markers of Coagulation and Inflammation in Potentially Susceptible Individuals

    Science.gov (United States)

    Objectives: Changes in air temperature are associated with an increase in cardiovascular events, but the role of pro-coagulant and pro-inflammatory blood markers is still poorly understood. We investigated the association between air temperature and fibrinogen, plasminogen act...

  9. Changes in Coagulation Profile During Planned Laparoscopic Operations

    OpenAIRE

    Gudz, I. M.; Tkachuk-Grigorchuk, O. O.; Tkachuk, O. L.

    2015-01-01

    Pneumoperitoneum may be a risk factor for venous thromboembolism. However, nowadays there is no reasonable algorithm for the prevention of thrombotic complications of laparoscopic interventions.The objective of the research was to assess the impact of laparoscopic surgery on coagulation parameters considering the number of other risk factors. The parameters of blood coagulation and thromboelastography in patients during laparoscopic cholecystectomy were investigated.Results. Blood coagulation...

  10. 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

  11. 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

  12. 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

    2015-08-01

    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

  13. 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

  14. 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

  15. 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)

  16. 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

  17. Blood transfusion during cardiac surgery is associated with inflammation and coagulation in the lung: a case control study

    OpenAIRE

    Tuinman, Pieter R; Vlaar, Alexander P; Cornet, Alexander D.; Hofstra, Jorrit J.; Levi, Marcel; Meijers, Joost CM; Beishuizen, Albertus; Schultz, Marcus J; Groeneveld, AB Johan; Juffermans, Nicole P.

    2011-01-01

    Introduction Blood transfusion is associated with increased morbidity and mortality in cardiac surgery patients, but cause-and-effect relations remain unknown. We hypothesized that blood transfusion is associated with changes in pulmonary and systemic inflammation and coagulation occurring in patients who do not meet the clinical diagnosis of transfusion-related acute lung injury (TRALI). Methods We performed a case control study in a mixed medical-surgical intensive care unit of a university...

  18. 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.

  19. Coagulation factors and recurrence of ischemic and bleeding adverse events in patients with acute coronary syndromes.

    Science.gov (United States)

    Campo, Gianluca; Pavasini, Rita; Pollina, Alberto; Tebaldi, Matteo; Ferrari, Roberto

    2013-08-01

    In the last years, management and prognosis of patients with acute coronary syndromes (ACS) are significantly improved. Nowadays antithrombotic (antiplatelet plus anticoagulant drugs) therapy represents the main treatment of ACS patients. Anticoagulant drugs are particularly helpful in the acute phase of ACS, whereas in the chronic phase are maintained only in selected cases. Many studies demonstrate that exists a significant variability in the coagulation factor levels between patients affected by ACS. This variation on coagulation factors levels is due to environmental (smoking, inflammation, sex, oral contraceptive, triglycerides, diabetes mellitus) and genetic determinants. Particularly several gene polymorphisms have been selected and clearly associated with significant variations in the coagulation factors values. The heightened levels of tissue factor, factor VII and fibrinogen are related with a "hypercoagulable status" and with a higher occurrence of ischemic complications after ACS and/or PCI. On the contrary, less data are available regarding the relationship between coagulation factors levels (or their gene polymorphisms) and bleeding complications. Recently, new anticoagulant drugs have been developed. They show less side effects and a better tolerability and, probably, their selected use in patients with a "hypercoagulable status" may improve the clinical outcome after ACS. In this review we analyze the current available data and we discuss how this finding may be useful for planning future studies to optimize the treatment of ACS patients. PMID:23827698

  20. Comparative analysis of activity of coagulation Factors V and VIII and level of fibrinogen in fresh frozen plasma and frozen plasma

    OpenAIRE

    Mitu Dogra; Meena Sidhu; Rahul Vasudev; Ashu Dogra

    2015-01-01

    Background: The aim of this study was to analyse and compare the activity of factor V, VIII and fibrinogen level in fresh frozen plasma and frozen plasma frozen after 8 hrs but within 24 hours after phlebotomy. Materials and Methods: Fresh frozen plasma separated from whole blood within 8 hours was compared with plasma separated within 24 hours after phlebotomy in terms of coagulation factors V and VIII and level of fibrinogen by standard methods using semi automated coagulometer sysmex CA50....

  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. 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...

  3. 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

  4. 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.

  5. 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.

  6. Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the coagulation system of 8 Gy gamma-irradiated Wistar rats

    International Nuclear Information System (INIS)

    Objective: To explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the coagulation parameters of Wistar rats irradiated with a single dose of 8 Gy γ-ray from cobalt-60. Methods: Clotting tests and thrombelastogram (TEG) were used to examine the effect of rhG-CSF on the coagulation parameters. A blood cell counter was applied to count the blood cells. A platelet aggregometer was adopted to observe the platelet aggregation. Results: Compared with irradiated control group, white blood cells and red blood cells of peripheral blood as well as the platelet number were increased (P<0.05), platelet aggregation was strengthened, the velocity of thrombosis was improved, and the maximum amplitude (MA) of the TEG was raised in rhG-CSF treated group (P<0.05). Conclusion: rhG-CSF can significantly promote the recovery of hemopoiesis and reverse the abnormal changes of the coagulation system in rats irradiated by the cobalt-60 with a single dose of 8 Gy. (authors)

  7. Platelet and coagulation factors in proliferative diabetic retinopathy.

    OpenAIRE

    Borsey, D. Q.; Prowse, C. V.; Gray, R S; Dawes, J.; James, K.; Elton, R A; Clarke, B F

    1984-01-01

    Plasma beta-thromboglobulin, platelet factor 4, fibrinogen, fibrinopeptide A, antithrombin III, factor VIII related antigen, alpha 2-macroglobulin, platelet count, and total glycosylated haemoglobin were measured in three well matched groups of subjects: non-diabetic controls, diabetics without retinopathy, and diabetics with proliferative retinopathy. beta-thromboglobulin and platelet factor 4 concentrations were significantly higher in the diabetics with retinopathy than in the controls and...

  8. 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

    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...... 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, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein and elastase were not or only weakly affected, The inhibition pattern with mammalian proteinases reveal a specificity of BSZx similar to that of antithrombin III. Trypsin from Fusarium was not inhibited while...

  9. Overview of the coagulation system

    OpenAIRE

    Sanjeev Palta; Richa Saroa; Anshu Palta

    2014-01-01

    Coagulation is a dynamic process and the understanding of the blood coagulation system has evolved over the recent years in anaesthetic practice. Although the traditional classification of the coagulation system into extrinsic and intrinsic pathway is still valid, the newer insights into coagulation provide more authentic description of the same. Normal coagulation pathway represents a balance between the pro coagulant pathway that is responsible for clot formation and the mechanisms that inh...

  10. 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

  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

    compared to that of wild-type FVIIa. In complex with tissue factor, activation of FIX, but not of FX, returned to normal. Deconvolution of the loop graft in order to identify important side chain substitutions resulted in the mutant Val(158{21})Asp/Leu(287{144})Thr/Ala(294{152})Ser/Glu(296{154}) Ile...

  12. 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.

  13. Experimental study and preliminary clinical application of microwave coagulation therapy for hepatic malignancies after interruption of hepatic blood flow

    International Nuclear Information System (INIS)

    Objective: To investigate the change on the extent of coagulated lesion under various interrupting methods of hepatic blood flow in vivo animal livers, and the clinical effect of combining transcatheter arterial chemoembolization (TACE) with percutaneous microwave coagulation therapy (PMCT) for primary and metastatic hepatic tumors. Methods: Using FORSEA MTC-3-500s microwave coagulator, we performed microwave tissue coagulation in vivo liver of 6 pigs at 60 W, 2 min and of 20 rabbits at 40 W, 2 min with or without the interruption of hepatic blood flow. 27 patients with primary hepatic carcinoma (30 nodules) and 8 patients with metastatic carcinoma (12 nodules) underwent the combination therapy of 1-4 sessions of TACE followed by within 3-10 days by 1-3 sessions of PMCT guided by ultrasonography and/or CT. The 42 lesions measured from 2.3 cm to 15.6 cm were taken place. Results: In vivo liver, the greatest dimension of the lesions coagulated by microwave with the interruption of hepatic arterial and portal flow were 22.5 ± 0.6 mm at 40 W , 2 min and 28.6 ± 1.2 mm at 60 W, 2 min, which were markedly larger than those without the interruption (13.3±0.3; and 15.6 ± 0.7 mm, P<0.001). In 35 cases of hepatic tumor, necrotic areas showed no enhancement. Complete necroses were observed for 29 nodules, with 24 smaller than 5 cm. On dynamic enhanced computed tomography (CT) or magnetic resonance imaging (MRI) within 2 W after combination therapy, 31 lesions were significantly shrunk. No serious complication was observed. The follow-up was carried on from 3 to 23 months (mean 11 month), 31 survival patients showed improvement in livelihood. One died of cardiac infarction (within 3 months), 2 of digestive hemorrhage, and 1 of dysfunction of liver (within 3 and 6 months). Conclusion: The microwave tissue coagulation region can enlarge markedly after interruption of hepatic blood flow. Preliminary clinical application of combination therapy of TACE and PMCT provides safe and

  14. 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

  15. 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

  16. 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 ...

  17. 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...

  18. Progress of in vitro factor VIII coagulant activity from 0 to 8 hours after reconstitution

    OpenAIRE

    Shim, Ye Jee; Lee, Kun Soo; Kim, Uk Hyun; Suh, Jin Kyung; Baik, Sae Yun; Hyun, Shin Young

    2014-01-01

    Background Continuous infusion of factor VIII (FVIII) is a more cost-effective method for treating hemophilia A than intermittent bolus injection. However, there is currently no specific data in Korea about the progress of in vitro FVIII coagulant activity (FVIII:C) after reconstitution from its lyophilized form. Methods Three commercial FVIII concentrate products (two recombinant FVIII and one plasma-derived) were used. In vitro FVIII:C was measured at 0, 2, 4, 6, and 8 hours following recon...

  19. 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...

  20. 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 ...

  1. Fractal discrimination of random fractal aggregates and its application in biomarker analysis for blood coagulation

    International Nuclear Information System (INIS)

    Highlights: ► Establishment of a potential bio-marker able to characterise bio-gels post their Gel-Point is presented. ► Spectral dimension is sensitive to fibrin internal network structure. ► Fractal simulation elucidates why spectral dimension displays this distinctive capacity. - Abstract: A recent rheological study has established that the fractal dimension, df, of an incipient clot, formed at the Gel Point (sol–gel transition) of coagulating blood is a significant new biomarker of haemostasis. In whole healthy blood, incipient clots show a clearly defined value of df = 1.7 within a narrow range, which represents a new ‘healthy index’ for normal clotting. The addition of unfractionated heparin significantly prolongs the onset of clot formation with a corresponding reduction of df as a function of heparin dose. However, as clots mature they exhibit (i) an expected increase in df and (ii) a significant increase to spread of these values, i.e. df’s in the range 2.0–2.5, limiting the use of df as a discriminant of clot microstructure. The present study, details how and why the spectral dimension, ds, can be used to accommodate this shortcoming and allow discrimination of mature forms of clot microstructure in indistinguishable in terms of their fractal dimension. To elucidate why ds permits discrimination a numerical experiment was conducted on computationally generated random fractal aggregates (RFAs) with a priori set value of df. Starting from RFAs with a df of 1.7, mature RFAs are evolved from these incipient templates by two differing growth processes achieving a final df of 2.1. Fractal and statistical analysis of the mature RFAs reveals, for the first time, that their differing internal structure is manifest in the magnitude of ds. The potential clinical significance of these findings is discussed in terms of the possibility of exploiting the incipient clot’s ability to template the internal arrangement of the mature clot to better predict

  2. 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.

  3. 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

  4. 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...

  5. 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

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

    Science.gov (United States)

    Bladbjerg, E M; Larsen, L F; Ostergaard, P; Jespersen, J

    2000-12-01

    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-TFPI antibodies increased FVIIa and FVII:C, and heparin reduced FVIIa. The heparinase Hepzyme was unable to abolish the effect of heparin. There were no in vitro effects on FVII:Ag. We conclude that, due to interference by TFPI and heparin in post-heparin plasma, it is impossible to measure the in vivo FVII activity by means of FVII clotting assays. These assays should therefore not be used to measure the coagulation status of patients in heparin therapy, unless extraordinary precautions are taken to eliminate TFPI and heparin effects ex vivo. The observed effect of heparin on FVII:Ag should be investigated further. PMID:11132652

  7. Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation

    OpenAIRE

    Takahashi, Kazue; Chang, Wei-Chuan; Takahashi, Minoru; Pavlov, Vasile; Ishida, Yumi; La Bonte, Laura; Shi, Lei; Fujita, Teizo; Stahl, Gregory L.; Van Cott, Elizabeth M.

    2010-01-01

    The first line of host defense is the innate immune system that includes coagulation factors and pattern recognition molecules, one of which is mannose-binding lectin (MBL). Previous studies have demonstrated that MBL deficiency increases susceptibility to infection. Several mechanisms are associated with increased susceptibility to infection, including reduced opsonophagocytic killing and reduced lectin complement pathway activation. In this study, we demonstrate that MBL and MBL-associated ...

  8. 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.

  9. 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

  10. The coagulation system and its function in early immune defense.

    OpenAIRE

    T. van der Poll; Herwald, Heiko

    2014-01-01

    Blood coagulation has a Janus-faced role in infectious diseases. When systemically activated, it can cause serious complications associated with high morbidity and mortality. However, coagulation is also part of the innate immune system and its local activation has been found to play an important role in the early host response to infection. Though the latter aspect has been less investigated, phylogenetic studies have shown that many factors involved in coagulation have ancestral origins whi...

  11. 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.

  12. 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

  13. 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

  14. Use of Plasma for Acquired Coagulation Factor Deficiencies in Critical Care.

    Science.gov (United States)

    Shah, Akshay; McKechnie, Stuart; Stanworth, Simon

    2016-03-01

    Coagulopathy in critically ill patients is common and often multifactorial. Fresh frozen plasma (FFP) is commonly used to correct this either prophylactically or therapeutically. FFP usage is mainly guided by laboratory tests of coagulation, which have been shown to have poor predictive values for bleeding. Viscoelastic tests are an attractive option to guide hemostatic therapy, but require rigorous evaluation. The past few years have seen a gradual reduction in national use of FFP potentially due to an increased awareness of risks such as transfusion-related acute lung injury, patient blood management strategies to reduce transfusion in general, and increased awareness of the lack of high-quality evidence available to support FFP use. Within critical care, FFP is administered before invasive procedures/surgery, to treat major traumatic and nontraumatic hemorrhage, disseminated intravascular coagulation, and for urgent warfarin reversal if first-line agents, such as prothrombin complex concentrate (PCC) are not available. Alternative agents such as fibrinogen concentrate and PCC need further evaluation through large-scale clinical trials. PMID:26716502

  15. 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...

  16. Endotoxin-induced pulmonary dysfunction is prevented by C1-esterase inhibitor.

    OpenAIRE

    R. Guerrero; Velasco, F; M. Rodriguez; Lopez, A; Rojas, R; Alvarez, M A; Villalba, R.; V. Rubio; Torres, A.; del Castillo, D

    1993-01-01

    In septic shock, hypotension, disseminated intravascular coagulation, and neutrophil activation are related to the activation of the blood coagulation contact system. This study evaluates in dogs the effect of the C1-esterase inhibitor (C1-INH), a main inhibitor of the blood coagulation contact system, on the cardiovascular and respiratory dysfunction associated with endotoxic shock. Two groups were included: controls, which received Escherichia coli endotoxin, and a C1-INH group in which C1-...

  17. Inactivation of human immunodeficiency virus by gamma radiation and its effect on plasma and coagulation factors

    International Nuclear Information System (INIS)

    The inactivation of HIV by gamma-radiation was studied in frozen and liquid plasma; a reduction of the virus titer of 5 to 6 logs was achieved at doses of 5 to 10 Mrad at -80 degrees C and 2.5 Mrad at 15 degrees C. The effect of irradiation on the biologic activity of a number of coagulation factors in plasma and in lyophilized concentrates of factor VIII (FVIII) and prothrombin complex was examined. A recovery of 85 percent of the biologic activity of therapeutic components present in frozen plasma and in lyophilized coagulation factor concentrates was reached at radiation doses as low as 1.5 and 0.5 Mrad, respectively. As derived from the first-order radiation inactivation curves, the radiosensitive target size of HIV was estimated to be 1 to 3 MDa; the target size of FVIII was estimated to be 130 to 160 kDa. Gamma radiation must be disregarded as a method for the sterilization of plasma and plasma-derived products, because of the low reduction of virus infectivity at radiation doses that still give acceptable recovery of biologic activity of plasma components

  18. Coagulation cascade in sepsis: getting from bench to bedside?

    OpenAIRE

    Brown, Glen

    2002-01-01

    The relationship between blood coagulation factors and the promotion or inhibition of the anti-inflammatory response continues to be defined through basic research. The potential key role of blood coagulation factors in the response during sepsis provides an exciting potential mechanism(s) for modification through the application of new therapies. The complexity of the potential multiple actions of the proteins, such as protein C, should allow for development of new therapies to minimize the ...

  19. 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.

  20. 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.

  1. 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

  2. Factor V deficiency

    Science.gov (United States)

    Factor V deficiency is a condition that is passed down through families, which affects the ability of the blood ... These proteins are called blood coagulation factors. Factor V deficiency is caused by a lack of Factor ...

  3. 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

    : C57BL/6J mice were subjected to CLP, and 1 hour later given intraperitoneally either SAHA dissolved in dimethyl sulfoxide (DMSO) or DMSO only. Sham-operated animals were handled in similar manner without CLP. Blood samples were collected by cardiac puncture and evaluated using the TEG 5000...... Thrombelastograph Hemostasis Analyzer System. RESULTS: Compared with the sham group, all animals in DMSO vehicle group died within 72 hours, and developed coagulopathy that manifested as prolonged initial fibrin formation and fibrin cross-linkage time, and decreased clot formation speed, platelet function, and clot...

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

    DEFF Research Database (Denmark)

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

    1999-01-01

    sVEGF was determined in nonfiltered and prestorage white cell-reduced whole blood (WB), buffy coat-depleted saline-adenine-glucose-mannitol (SAGM) blood, platelet-rich plasma (PRP), and buffy coat-derived platelet (BCP) pools obtained from volunteer, healthy blood donors. As a control, total content...... 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......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...

  5. 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...

  6. 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.

  7. 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

  8. 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

  9. Coagulation factor concentrate-based therapy for remote damage control resuscitation (RDCR): a reasonable alternative?

    Science.gov (United States)

    Maegele, Marc

    2016-04-01

    The concept of remote damage control resuscitation (RDCR) is still in its infancy and there is significant work to be done to improve outcomes for patients with life-threatening bleeding secondary to injury. The prehospital phase of resuscitation is critical and if shock and coagulopathy can be rapidly minimized before hospital admission this will very likely reduce morbidity and mortality. The optimum transfusion strategy for these patients is still highly debated and the potential implications of the recently published pragmatic, randomize, optimal platelet, and plasma ratios trial (PROPPR) for RDCR have been reviewed. Identifying the appropriate transfusion strategy is mandatory before adopting prehospital hemostatic resuscitation strategies. An alternative approach is based on the early administration of coagulation factor concentrates combined with the antifibrinolytic tranexamic acid (TXA). The three major components to this approach in the context of RDCR target the following steps to achieve hemostasis: 1) stop (hyper)fibrinolysis; 2) support clot formation; and 3) increase thrombin generation. Strong evidence exists for the use of TXA. The data from the prospective fibrinogen in trauma induced coagulopathy (FIinTIC) study will inform on the prehospital use of fibrinogen in bleeding trauma patients. Deficits in thrombin generation may be addressed by the administration of prothrombin complex concentrates. Handheld point-of-care devices may be able to support and guide the prehospital and remote use of intravenous hemostatic agents including coagulation factor concentrates along with clinical presentation, assessment, and the extent of bleeding. Combinations may even be more effective for bleeding control. More studies are urgently needed. PMID:27100752

  10. 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.

  11. 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.

  12. 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

  13. Biologic TNFα-inhibitors that cross the human blood-brain barrier

    OpenAIRE

    Pardridge, William M.

    2010-01-01

    Tumor necrosis factor (TNF)α inhibitors (TNFI) are a major class of biologic therapeutics, and include decoy receptor and monoclonal antibody (MAb) therapeutics that block TNFα action. TNFα is a pro-inflammatory cytokine in brain disease, such as stroke, brain or spinal cord injury, or Alzheimer disease. However, the biologic TNFIs cannot be developed for the brain, because these large molecules do not cross the blood-brain barrier (BBB). Brain penetrating forms of TNFα decoy receptors or ant...

  14. 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...

  15. 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...

  16. 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

  17. 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.

  18. 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

  19. Reduced Blood Coagulation on Roll-to-Roll, Shrink-Induced Superhydrophobic Plastics.

    Science.gov (United States)

    Nokes, Jolie M; Liedert, Ralph; Kim, Monica Y; Siddiqui, Ali; Chu, Michael; Lee, Eugene K; Khine, Michelle

    2016-03-01

    The unique antiwetting properties of superhydrophobic (SH) surfaces prevent the adhesion of water and bodily fluids, including blood, urine, and saliva. While typical manufacturable approaches to create SH surfaces rely on chemical and structural modifications, such approaches are expensive, require postprocessing, and are often not biocompatible. By contrast, it is demonstrated that purely structural SH features are easily formed using high throughput roll-to-roll (R2R) manufacturing by shrinking a prestressed thermoplastic with a thin, stiff layer of silver and calcium. These features are subsequently embossed into any commercially available and Food and Drug Administration (FDA)-approved plastic. The R2R SH surfaces have contact angles >150° and contact angle hysteresis 4200× reduction of blood residue area compared to the nonstructured controls of the same material. In addition, blood clotting is reduced >5× using whole blood directly from the patient. Furthermore, these surfaces can be easily configured into 3D shapes, as demonstrated with SH tubes. With the simple scale-up production and the eliminated need for anticoagulants to prevent clotting, the proposed conformable SH surfaces can be impactful for a wide range of medical tools, including catheters and microfluidic channels. PMID:26784916

  20. In vitro anti-inflammatory and anti-coagulant effects of antibiotics towards Platelet Activating Factor and thrombin

    OpenAIRE

    Demopoulos Constantinos A; Tsekes George; Lioni Athina; Tsogas Nickolaos; Chini Maria; Tsoupras Alexandros B; Lazanas Marios C

    2011-01-01

    Abstract Background Sepsis is characterized as a systemic inflammatory response that results from the inability of the immune system to limit bacterial spread during an ongoing infection. In this condition the significant mediator of inflammation Platelet Activating Factor (PAF) and the coagulant factor thrombin are implicated. In animal models, treatment with PAF-antagonists or co-administration of antibiotics with recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited promising results. I...

  1. 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.

  2. 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

  3. Mechanisms and specificity of factor XIa and trypsin inhibition by protease nexin 2 and basic pancreatic trypsin inhibitor

    OpenAIRE

    Navaneetham, Duraiswamy; Sinha, Dipali; Walsh, Peter N.

    2010-01-01

    Factor XIa (FXIa) inhibition by protease nexin-2 (PN2KPI) was compared with trypsin inhibition by basic pancreatic trypsin inhibitor (BPTI). PN2KPI was a potent inhibitor of FXIa (Ki ∼ 0.81 nM) and trypsin (Ki ∼ 0.03 nM), but not of other coagulation proteases (thrombin, FVIIa, FIXa, FXa, FXIIa, plasmin, kallikrein, Ki > 185 nM). PN2KPI was ∼775-fold more potent than BPTI in FXIa inhibition, but both exhibited similar potencies against trypsin. Studies of FXIa and trypsin inhibition by PN2KPI...

  4. ABO blood groups, rhesus factor and pemphigus

    OpenAIRE

    Valikhani Mahin; Kavand Sima; Toosi Siavash; Kavand Golnaz; Ghiasi Maryam

    2007-01-01

    Background: Pemphigus is an autoimmune blistering disease of the skin and mucous membranes with significant mortality and morbidity. Genetic factors are known to be involved in pemphigus. Several studies have reproducibly shown significant associations of ABO blood groups with various autoimmune human diseases. Aim: To study the relationship between ABO and Rhesus (D) blood groups and pemphigus in Iranian patients. Materials and Methods: Data on age, sex, ABO and Rhesus blood type and cl...

  5. 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

  6. 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。

  7. 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...

  8. 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...

  9. 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.

  10. 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

  11. Effect of the root extract of Fagara zanthoxyloides on blood coagulation.

    Science.gov (United States)

    Essien, E M; Okogun, J I

    1976-12-31

    The clot-promoting activity of the aqueous extract of Fagara-zanthoxyloides Lam plant is described for the first time. It significantly shortened the PTT (K) of normal and factor VIII deficient plasma while it manifested no such action on factor IX-deficient plasma. This activity could be demonstrated in the residue of the lyophilized aqueous extract after its successive extraction with ether, chloroform and methanol. It could not be attributed to the purified fractions: Zanthoxylol or its modified form 3, 4-dihydro-2,2-dimethyl-2H-1 benzopyran-6-butyric acid (DBA), hesperidin, Fagaramide or the ether soluble fraction of the aqueous extract. PMID:1037149

  12. 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.

  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. PMID:26886361

  14. 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

  15. 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

  16. 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

  17. 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

  18. 1H NMR assignment and secondary structure of the Ca2+-free form of the amino-terminal epidermal growth factor like domain in coagulation factor X

    International Nuclear Information System (INIS)

    Blood coagulation factor X is composed of discrete domains, two of which are homologous to the epidermal growth factor (EGF). The N-terminal EGF like domain in factor X (fX-EGFN), residues 45-86 of the intact protein contains a β-hydroxylated asparatic acid and has one Ca2+-binding site. Using 2D NMR techniques, the authors have made a full assignment of the 500-MHz 1H NMR spectrum of Ca2+-free fX-EGFN. On the basis of this assignment and complementary NOESY experiments, they have also determined the secondary structure of Ca2+-free fX-EGFN in water solution. Residues 45-49 are comparatively mobile, whereas residues 5-56 are constrained by two disulfide bonds to one side of an antiparallel β-sheet involving residues 59-64 and 67-72. Another antiparallel β-sheet involves residues 76-77 and 83-84. A small, parallel β-sheet connects residues 80-81 and 55-56 and thereby orients the two antiparallel β-sheets relative to each other. Four β-turns are identified, involving residues 50-53, 56-59, 64-67, 73-76. Residues 78-82 adopt an extended bend structure. On the basis of secondary structure and the location of the three disulfide bonds, they find that Asp 46, Asp 48, and Hya 63 are sufficiently close to each other to form a Ca2+-binding site. However, the amino terminus of the Ca2+-free form of fX-EGFN is not part of a triple-stranded β-sheet as in other EGF like peptides. Differences and similarities between fX-EGFN and murine EGF with respect to secondary structure and conformational shifts are discussed

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. ABO blood groups, rhesus factor and pemphigus

    Directory of Open Access Journals (Sweden)

    Valikhani Mahin

    2007-01-01

    Full Text Available Background: Pemphigus is an autoimmune blistering disease of the skin and mucous membranes with significant mortality and morbidity. Genetic factors are known to be involved in pemphigus. Several studies have reproducibly shown significant associations of ABO blood groups with various autoimmune human diseases. Aim: To study the relationship between ABO and Rhesus (D blood groups and pemphigus in Iranian patients. Materials and Methods: Data on age, sex, ABO and Rhesus blood type and clinicopathological diagnosis of the patients with pemphigus were collected. A total of 573 patients with pemphigus were assessed for their association with ABO or Rhesus (D blood groups and compared with the normal population in the area. Results: The distribution of ABO and Rhesus blood groups in patients with pemphigus was similar to the normal local population in Iran. No relationship was found between ABO or Rhesus blood groups and the phenotype of pemphigus. Conclusion: It appears that there is no association between ABO or Rhesus (D blood groups and the frequency of pemphigus variants in comparison with normal population in Iran.

  8. Analyzing sociodemographic factors amongst blood donors

    Directory of Open Access Journals (Sweden)

    Shenga Namgay

    2010-01-01

    Full Text Available Introduction: Blood transfusion is a fundamental and requisite part of any National Health Service for optimum management of emergency conditions like severe trauma shock and resuscitation with the optimum stock of its different components. The objective of the present study was to analyze the factors of knowledge of prospective blood donors that may influence their perception and awareness about blood donation. Materials and Methods: This population-based cross-sectional study was conducted at Gangtok in the state of Sikkim, India, on 300 subjects of the adult population selected by two-stage cluster sampling. The main outcome variables were the socioeconomic and demographic variables of knowledge of blood donation. By interview technique, using the pre-tested structured close-ended questionnaire, the principal investigator collected the data. Results: In our study population, 46% of the study population was found to have a high knowledge score. The knowledge about blood donation was found to be statistically significant with the occupational status and the education levels, both in the bivariate and in the multivariate analyses. Knowledge about blood donation was not significantly related to age, sex, marital status, religion, community status and per capita monthly family income. Conclusion: The study suggested that the perceptions toward voluntary blood donation could be influenced to a large extent by sociodemographic variables of knowledge among the general population.

  9. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-01

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

  11. 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

  12. 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 ...

  13. 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 ...

  14. Effects of Blood Flow and/or Ventilation Restriction on Radiofrequency Coagulation Size in the Lung: An Experimental Study in Swine

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate how the restriction of blood flow and/or ventilation affects the radiofrequency (RF) ablation coagulation size in lung parenchyma. Thirty-one RF ablations were done in 16 normal lungs of 8 living swine with 2-cm LeVeen needles. Eight RF ablations were performed as a control (group G1), eight with balloon occlusion of the ipsilateral mainstem bronchus (G2), eight with occlusion of the ipsilateral pulmonary artery (G3), and seven with occlusion of both the ipsilateral bronchus and pulmonary artery (G4). Coagulation diameters and volumes of each ablation zone were compared on computed tomography (CT) and gross specimen examinations. Twenty-six coagulation zones were suitable for evaluation: eight in G1, five in G2, seven in G3, and six in G4 groups. In G1, the mean coagulation diameter was 21.5 ± 3.5 mm on CT and 19.5 ± 1.78 mm on gross specimen examination. In G2, the mean diameters were 26.5 ± 5.1 mm and 23.0 ± 2.7 mm on CT and gross specimen examination, respectively. In G3, the mean diameters were 29.4 ± 2.2 mm and 27.4 ± 2.9 mm on CT and gross specimen examination, respectively, and in G4, they were 32.6 ± 3.33 mm and 28.8 ± 2.6 mm, respectively. The mean coagulation volumes were 3.39 ± l.52 cm3 on CT and 3.01 ± 0.94 cm3 on gross examinations in G1, 6.56 ± 2.47 cm3 and 5.22 ± 0.85 cm3 in G2, 10.93 ± 2.17 cm3 and 9.97 ± 2.91 cm3 in G3, and 13.81 ± 3.03 cm3 and 11.06 ± 3.27 cm3 in G4, respectively. The mean coagulation diameters on gross examination and mean coagulation volumes on CT and gross examination with G3 and G4 were significantly larger than those in G1 (p < 0.0001, p < 0.0001, p < 0.0001, respectively) or in G2 (p < 0.05, p < 0.005, p < 0.005, respectively). Pulmonary collapse occurred in one lung in G2 and pulmonary artery thrombus in two lungs of G3 and two lungs of G4. The coagulation size of RF ablation of the lung parenchyma is increased by ventilation and particularly by pulmonary artery

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

    OpenAIRE

    Hossein Zolfagharian; Mohammad Mohajeri; Mahdi Babaie

    2015-01-01

    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 ...

  16. 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.

  17. The prospects of application of natural antioxidants in correction of blood coagulation in patients with breast cancer during radiation therapy

    International Nuclear Information System (INIS)

    As an accompanying therapy of the patients with BC Bipolan produced positive effect on coagulation homeostasis. By the end of the course of treatment the indices of homeostasis normalized in the experimental group of the patients; manifestations of DIC syndrome and thromboembolic complications were controlled

  18. 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

  19. Astrocyte Mitogen Inhibitor Related to Epidermal Growth Factor Receptor

    Science.gov (United States)

    Nieto-Sampedro, Manuel

    1988-06-01

    Epidermal growth factor (EGF) is a well-characterized polypeptide hormone with diverse biological activities, including stimulation of astrocyte division. A soluble astrocyte mitogen inhibitor, immunologically related to the EGF receptor, is present in rat brain. Injury to the brain causes a time-dependent reduction in the levels of this inhibitor and the concomitant appearance of EGF receptor on the astrocyte surface. Intracerebral injection of antibody capable of binding the inhibitor caused the appearance of numerous reactive astrocytes. EGF receptor-related inhibitors may play a key role in the control of glial cell division in both normal and injured brain.

  20. 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

  1. 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.

  2. The interplay between platelets and coagulation

    OpenAIRE

    Weeterings, C.

    2009-01-01

    Platelet activation and blood coagulation are two processes often studied separately, but which cannot be seen independently from each other. Platelets play a pivotal role in coagulation, not only by providing negatively charged phospholipids, but also in localizing the coagulation process from a diffuse plasma environment to an anionic surface, most likely via specific receptors on the platelets. On the other hand, the main product of coagulation, thrombin, is a potent platelet activator, th...

  3. 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

  4. Improved Amplification of Microbial DNA from Blood Cultures by Removal of the PCR Inhibitor Sodium Polyanetholesulfonate

    OpenAIRE

    Fredricks, David N.; Relman, David A

    1998-01-01

    Molecular methods are increasingly used to identify microbes in clinical samples. A common technical problem with PCR is failed amplification due to the presence of PCR inhibitors. Initial attempts at amplification of the bacterial 16S rRNA gene from inoculated blood culture media failed for this reason. The inhibitor persisted, despite numerous attempts to purify the DNA, and was identified as sodium polyanetholesulfonate (SPS), a common additive to blood culture media. Like DNA, SPS is a hi...

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

    OpenAIRE

    Antić Ana; Stanojković Zoran; Mačukanović-Golubović Lana; Jelić Marija

    2012-01-01

    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...

  6. Pharmacodynamics and Pharmacokinetics of oral factor Xa inhibitors

    OpenAIRE

    Persson PB

    2015-01-01

    Pontus B Persson Institute of Vegetative Physiology, Berlin, GermanyApixaban and rivaroxaban are oral factor Xa inhibitors. In a recent issue of Clinical Pharmacology: Advances and Applications, Frost et al compare apixaban (2.5 mg, twice daily) to rivaroxaban (10 mg, once daily) with regard to their pharmacokinetics and pharmacodynamics.1 Both oral factor Xa inhibitors have similar half-lives. Moreover, as may seem intuitive, the twice daily regime of apixaban revealed a less pronounced peak...

  7. Effect of hormone replacement therapy on lipids and coagulation factors in postmenopausal women smokers

    Directory of Open Access Journals (Sweden)

    Tatović-Babić Danijela

    2002-01-01

    Full Text Available Postmenopause and smoking impair lipid profile, induce hypercoagulability and reduce fibrinolytic capacity [1, 2]. Postmenopause induced lipid changes can be reversed by oestrogen replacement [3]. Oestrogens also reduce fibrino-gen level [4] and have beneficial effects on endothelium [5]. Although several studies showed that hormone replacement therapy may increase the risk of thromboembolic diseases, procoagulant oestrogen activity has not clearly been demonstrated. It is well known that smoking accelerates oestrogen metabolism [6, 7], which may attenuate its beneficial effects. The present study was undertaken to determine if there is difference in beneficial effects of oestrogens between smokers and non-smokers in terms of coagulation process and lipids. The examination was a longitudinal one-year, before/after therapeutic study, which included healthy postmenopausal women (FSH levels at least 40 U/l, 30 smokers and 32 non-smokers who were under 55 years of age and postmenopausal period shorter than 5 years. Women with surgically induced menopause received unopposed oral oestrogens, while those with spontaneous menopause were treated with combined oral oestrogen/progestogen therapy. Before entering the study and in three-months intervals total LDL, HDL cholesterol, triglycérides and VLDL were determined, as well School of Medicine, Belgrade as plasma fibrinogen prothrombin time, and activated partial thromboplastin time. Neither beneficial nor adverse effects of oestrogens on lipids and coagulation were observed during one-year follow-up in smokers, although subjects with longer smoking history had higher triglycérides levels after 12 months of therapy. On the contrary, oestrogen replacement reduced total and LDL cholesterol and increased HDL cholesterol in non-smokers, with no change in triglycérides and VLDL level. A decrease in fibrinogen levels and coagulation activity, expressed by protrombin time and partial thromboplastin time, were

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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。

  15. The preliminary observation of the changes of β-actin,coagulant and inflammatory factors in mice serum induced by γ rays irradiation

    International Nuclear Information System (INIS)

    In order to learn the effect of β-actin in acute radiation injury, the changeable pattern with time of plasma β-actin, PT, APTT, FIB and IL-8 in mice spleen tissue exposed to 6 Gy γ-rays radiation was investigated.Blood and spleen were collected at immediate, 1, 2, 3, 4, 7 and 14 d after irradiation, respectively. The contents of blood β-actin were detected by magnetic bead separation enzyme-linked immunosorbent. An STAGO blood coagulation instrument was used to determine PT, APTT and FIB. DNA expression of IL-8 was detected by real time-PCR analyzer. The results show that the level of β-actin in serum of irradiated mice is higher than that of normal control group at all different post-irradiation time points although the change of β-actin in serum of irradiated mice with time schedule shows a pattern which increases within 1d and declines beyond 1d. The trend of the changes in plasma PT, APTT, FIB and in spleen IL-8 and time pattern of these changes are similar to that in plasma β-actin in irradiated mice. The difference in values and the time phase between plasma β-actin and other indexes is the reaching time of peak values and the declining levels of the values. These results are valuable for studying the role of β-actin in acute radiation sickness pathology process and can be used to explore new factors influencing and regulating pathology process. (authors)

  16. 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

  17. 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.

  18. The structure of the FnI-EGF-like tandem domain of coagulation factor XII solved using SIRAS

    International Nuclear Information System (INIS)

    The structure of the FnI-EGF-like tandem domain was solved to 1.6 Å using data sets of native and holmium chloride bound protein. Putative biological roles of this tandem domain are discussed based on the structure. Coagulation factor XII (FXII) is a key protein in the intrinsic coagulation and kallikrein–kinin pathways. It has been found that negative surfaces and amyloids, such as Aβ fibrils, can activate FXII. Additionally, it has been suggested that FXII simulates cells and that it plays an important role in thrombosis. To date, no structural data on FXII have been deposited, which makes it difficult to support any hypothesis on the mechanism of FXII function. The crystal structure of the FnI-EGF-like tandem domain of FXII presented here was solved using experimental phases. To determine the phases, a SIRAS approach was used with a native and a holmium chloride-soaked data set. The holmium cluster was coordinated by the C-terminal tails of two symmetry-related molecules. Another observation was that the FnI domain was much more ordered than the EGF-like domain owing to crystal packing. Furthermore, the structure shows the same domain orientation as the homologous FnI-EGF-like tandem domain of tPA. The plausibility of several proposed interactions of these domains of FXII is discussed. Based on this FXII FnI-EGF-like structure, it could be possible that FXII binding to amyloid and negatively charged surfaces is mediated via this part of FXII

  19. 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

  20. 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

  1. Studies on contact activation: effects of surface and inhibitors.

    Science.gov (United States)

    Cameron, C L; Fisslthaler, B; Sherman, A; Reddigari, S; Silverberg, M

    1989-01-01

    Contact activation is initiated when the plasma proteins, Hageman factor (factor XII), prekallikrein and high molecular weight kininogen interact with negatively charged materials. The activation of the intrinsic pathway of blood coagulation and the production of bradykinin are among the sequelae of contact activation. The kinetics of the activation of the contact system are modified by plasma inhibitors, C1 inhibitor being quantitatively the most important. We propose that the activation of the system requires that the stimulus provided by the surface must be greater than a threshold value to overcome the effects of the inhibitors. We show in this paper that the amount of surface required for activation is much reduced in the absence of C1 inhibitor (Hereditary Angioedema) or in the cold where the inhibitor loses much of its effectiveness. Antithrombin III inhibition of activated Hageman factor is augmented by heparin which is also an activator of Hageman factor. The rate constants for inhibition remain much lower than for C1 inhibitor, however. PMID:2530427

  2. Chapter 3. Biological properties of ethynyl-piperidol polymers. 3.1. Activating effect of quaternized linear and graft-polymers of ethynyl-piperidol on blood coagulation system

    International Nuclear Information System (INIS)

    This article is devoted to activating effect of quaternized linear and graft-polymers of ethynyl-piperidol on blood coagulation system. The indexes of blood clotting at intraperitoneal injection of polymers were considered. The anti heparin activity of methiodide of poly-isopropenyl trimethyl ethynyl piperidol was considered as well. The influence of molecular weight on styptic activity and toxicity of methiodide of poly-isopropenyl trimethyl ethynyl piperidol was studied. The styptic activity of grafted polymers of ethynyl piperidol was defined.

  3. FXIIa inhibitor rHA-Infestin-4: Safe thromboprotection in experimental venous, arterial and foreign surface-induced thrombosis.

    Science.gov (United States)

    May, Frauke; Krupka, Jennifer; Fries, Marion; Thielmann, Ina; Pragst, Ingo; Weimer, Thomas; Panousis, Con; Nieswandt, Bernhard; Stoll, Guido; Dickneite, Gerhard; Schulte, Stefan; Nolte, Marc W

    2016-06-01

    Haemostasis including blood coagulation is initiated upon vessel wall injury and indispensable to limit excessive blood loss. However, unregulated pathological coagulation may lead to vessel occlusion, causing thrombotic disorders, most notably myocardial infarction and stroke. Furthermore, blood exposure to foreign surfaces activates the intrinsic pathway of coagulation. Hence, various clinical scenarios, such as extracorporeal membrane oxygenation, require robust anticoagulation consequently leading to an increased bleeding risk. This study aimed to further assess the antithrombotic efficacy of the activated factor XII (FXIIa) inhibitor, rHA-Infestin-4, in several thrombosis models. In mice, rHA-Infestin-4 decreased occlusion rates in the mechanically-induced arterial (Folt's) and the FeCl3 -induced venous thrombosis model. rHA-Infestin-4 also protected from FeCl3 -induced arterial thrombosis and from stasis-prompted venous thrombosis in rabbits. Furthermore, rHA-Infestin-4 prevented occlusion in the arterio-venous shunt model in mice and rabbits where thrombosis was induced via a foreign surface. In contrast to heparin, the haemostatic capacity in rabbits was unaffected by rHA-Infestin-4. Using rodent and non-rodent species, our data demonstrate that the FXIIa inhibitor rHA-Infestin-4 decreased arterial, venous and foreign surface-induced thrombosis without affecting physiological haemostasis. Hence, we provide further evidence that targeting FXIIa represents a potent yet safe antithrombotic treatment approach, especially in foreign surface-triggered thrombosis. PMID:27018425

  4. Are olive oil diets antithrombotic? Diets enriched with olive, rapeseed, or sunflower oil affect postprandial factor VII differently

    DEFF Research Database (Denmark)

    Larsen, L.F.; Jespersen, J; Marckmann, P.

    1999-01-01

    compared the effects of virgin olive oil with those of rapeseed and sunflower oils on blood coagulation factor VII (FVII), a key factor in thrombogenesis. DESIGN: In a randomized and strictly controlled crossover study, 18 healthy young men consumed diets enriched with 5 g/MJ (19% of total energy) olive...... oil, sunflower oil, or rapeseed oil for periods of 3 wk. On the final day of each period, participants consumed standardized high-fat meals (42% of energy as fat). Fasting and nonfasting blood samples were collected after each period. RESULTS: Mean (+/-SEM) nonfasting peak concentrations of activated...... with respect to nonfasting factor VII coagulant activity (FVII:c), prothrombin fragment 1+2 (F1+2), and tissue factor pathway inhibitor (TFPI) concentrations, or with respect to fasting plasma values of FVII protein, FVII:c, FVIIa, F1+2, or TFPI. CONCLUSION: A background diet rich in olive oil may...

  5. 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...

  6. Congenital factor XI deficiency in a domestic shorthair cat.

    Science.gov (United States)

    Troxel, Mark T; Brooks, Marjory B; Esterline, Meredith L

    2002-01-01

    A 6-month-old, female, domestic shorthair cat was examined after onychectomy and ovariohysterectomy because of bleeding from the paws. Prolonged activated partial thromboplastin time was discovered, Coagulation factor analyses revealed deficiency of factor XI coagulant activity. Plasma mixing studies indicated factor deficiency or dysfunction rather than factor inhibition. Feline factor XI deficiency in one adult cat has been previously reported but was attributed to factor XI inhibitors. The signalment, lack of primary disease, and the finding of persistent factor XI deficiency in the absence of coagulation inhibitors were considered compatible with congenital factor XI deficiency in the cat of this report. PMID:12428887

  7. 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

  8. 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...

  9. 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.

  10. 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

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

    Directory of Open Access Journals (Sweden)

    Syed Shahid Habib

    2013-05-01

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

  12. 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

  13. Complete sequence of the human tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade

    International Nuclear Information System (INIS)

    Tissue factor (TF) is the high-affinity receptor for plasma factors VII and VIIa. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade. outside the vasculature, TF expression is highly dependent upon cell type. TF can also be induced by inflammatory mediators to appear on monocytes and vascular endothelial cells as a component of cellular immune responses. As an initial step toward elucidating the regulatory regions involved in control of TF gene expression, we have established the organization of the 12.4 kbp human TF gene and its complete DNA sequence. There are six exons separated by five introns. Within intron 5, we have mapped the single nucleotide difference which leads to the previously described MspI polymorphism; the same intron also contains an apparently polymorphic PstI site. The TF gene also contains three full-length Alu repeats and one partial Alu repeat. A single major transcription start site was identified 26 bp downstream from a TATA consensus promoter element. The putative promoter and first exon are located within a 1.2 kbp region of very high G + C content which fits the criteria of an HTF island. A cluster of predicted binding sites for a number of known transcription factors was found to coincide with this putative promoter region. These factors included AP-1 and AP-2 which can mediate the effects of phorbol esters, agonists known to induce TF expression in monocytes and vascular endothelial cells

  14. Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

    Directory of Open Access Journals (Sweden)

    Nicholas B. Abt

    2014-01-01

    Full Text Available Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable. Methods. The patient’s plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours. Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity. Conclusions. Physicians can be presented with the challenging clinical picture of an acquired factor VIII inhibitor without a detectable inhibitor by the Bethesda assay. Standard therapy for an acquired hemophilia A should be considered.

  15. CRISPR/Cas9-mediated somatic correction of a novel coagulator factor IX gene mutation ameliorates hemophilia in mouse.

    Science.gov (United States)

    Guan, Yuting; Ma, Yanlin; Li, Qi; Sun, Zhenliang; Ma, Lie; Wu, Lijuan; Wang, Liren; Zeng, Li; Shao, Yanjiao; Chen, Yuting; Ma, Ning; Lu, Wenqing; Hu, Kewen; Han, Honghui; Yu, Yanhong; Huang, Yuanhua; Liu, Mingyao; Li, Dali

    2016-01-01

    The X-linked genetic bleeding disorder caused by deficiency of coagulator factor IX, hemophilia B, is a disease ideally suited for gene therapy with genome editing technology. Here, we identify a family with hemophilia B carrying a novel mutation, Y371D, in the human F9 gene. The CRISPR/Cas9 system was used to generate distinct genetically modified mouse models and confirmed that the novel Y371D mutation resulted in a more severe hemophilia B phenotype than the previously identified Y371S mutation. To develop therapeutic strategies targeting this mutation, we subsequently compared naked DNA constructs versus adenoviral vectors to deliver Cas9 components targeting the F9 Y371D mutation in adult mice. After treatment, hemophilia B mice receiving naked DNA constructs exhibited correction of over 0.56% of F9 alleles in hepatocytes, which was sufficient to restore hemostasis. In contrast, the adenoviral delivery system resulted in a higher corrective efficiency but no therapeutic effects due to severe hepatic toxicity. Our studies suggest that CRISPR/Cas-mediated in situ genome editing could be a feasible therapeutic strategy for human hereditary diseases, although an efficient and clinically relevant delivery system is required for further clinical studies. PMID:26964564

  16. 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)

  17. Johne's disease in cattle is associated with enhanced expression of genes encoding IL-5, GATA-3, tissue inhibitors of matrix metalloproteinases 1 and 2, and factors promoting apoptosis in peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Coussens, P.M.; Pudrith, C.B.; Skovgaard, Kerstin; Ren, X.N.; Suchyta, S.P.; Stabel, J.R.; Heegaard, Peter M. H.

    transmission in utero. Once established, infections typically exist in a subclinical state for several years. Recent gene-expression profiling studies suggested the hypothesis that inherent gene-expression profiles in peripheral blood mononuclear cells (PBMCs) front M. paratuberculosis-infected cattle may be......Infection of ruminants with Mycobacterium avium. subspecies paratuberculosis (M. para tuberculosis) leads to a chronic and often fatal granulomatous enteritis known as Johne's disease. Most infections with M. paratuberculosis occur during the first 6 months of life, and there is some evidence for...... different than expression profiles in PBMCs from uninfected controls. If true, this would suggest that it is possible to identify an M. paratuberculosis infection "signature" through transcriptional profiling of peripheral immune cells. In addition, identification of groups or classes of genes showing...

  18. 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

  19. Disseminated intravascular coagulation in solid tumors

    International Nuclear Information System (INIS)

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

  20. 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...

  1. 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...

  2. [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

  3. Strength training and testosterone treatment have opposing effects on migration inhibitor factor levels in ageing men

    DEFF Research Database (Denmark)

    Glintborg, D.; Christensen, L. L.; Kvorning, T.; Larsen, Rasmus; Brixen, K.; Hougaard, D. M.; Richelsen, B.; Bruun, J. M.; Andersen, M.

    2013-01-01

    Strength Training and Testosterone Treatment Have Opposing Effects on Migration Inhibitor Factor Levels in Ageing Men......Strength Training and Testosterone Treatment Have Opposing Effects on Migration Inhibitor Factor Levels in Ageing Men...

  4. 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.

  5. 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. ...

  6. The effect of repeated freezing and thawing on levels of vitamin K-dependent coagulation factors and fibrinogen in fresh frozen plasma

    OpenAIRE

    Joseph Philip; Sarkar, R.S.; Amardeep Pathak

    2013-01-01

    Background: Fresh frozen plasma (FFP) is considered adequate for transfusion immediately after thawing or for up to 24 hours if kept at 1-6°C, and is currently used very often to replace deficient clotting factors. If factor levels in refrozen FFP are within normal limits, then this component can possibly be transfused, thus avoiding wastage of FFP. Aim: To study the fate of vitamin K-dependent coagulation factors (F II, F VII, F IX, F X) and fibrinogen activity levels in repeatedly (twice) f...

  7. 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

  8. [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

  9. 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.

  10. Spatial coagulation with bounded coagulation rate

    OpenAIRE

    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 below by a positive constant. Multiple coagulations, fragmentation and scattering are also considered.

  11. Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

    Directory of Open Access Journals (Sweden)

    Gozzo A.J.

    2003-01-01

    Full Text Available Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis. The proteolytic enzymes involved in these processes are usually controlled by specific inhibitors and may be influenced by several factors including glycosaminoglycans, as recently demonstrated by our group. The aim of the present study was to investigate the effect of glycosaminoglycans (30 to 250 µg/ml on kallikrein activity on plasminogen and factor XII and on the inhibition of kallikrein by the plasma proteins C1-inhibitor and antithrombin. Almost all available glycosaminoglycans (heparin, heparan sulfate, bovine and tuna dermatan sulfate, chondroitin 4- and 6-sulfates reduced (1.2 to 3.0 times the catalytic efficiency of kallikrein (in a nanomolar range on the hydrolysis of plasminogen (0.3 to 1.8 µM and increased (1.9 to 7.7 times the enzyme efficiency in factor XII (0.1 to 10 µM activation. On the other hand, heparin, heparan sulfate, and bovine and tuna dermatan sulfate improved (1.2 to 3.4 times kallikrein inhibition by antithrombin (1.4 µM, while chondroitin 4- and 6-sulfates reduced it (1.3 times. Heparin and heparan sulfate increased (1.4 times the enzyme inhibition by the C1-inhibitor (150 nM.

  12. A catalog for the transcripts from the venomous structures of the caterpillar Lonomia obliqua: identification of the proteins potentially involved in the coagulation disorder and hemorrhagic syndrome.

    Science.gov (United States)

    Veiga, Ana B G; Ribeiro, José M C; Guimarães, Jorge A; Francischetti, Ivo M B

    2005-08-01

    Accidents with the caterpillar Lonomia obliqua are often associated with a coagulation disorder and hemorrhagic syndrome in humans. In the present study, we have constructed cDNA libraries from two venomous structures of the caterpillar, namely the tegument and the bristle. High-throughput sequencing and bioinformatics analyses were performed in parallel. Over one thousand cDNAs were obtained and clustered to produce a database of 538 contigs and singletons (clusters) for the tegument library and 368 for the bristle library. We have thus identified dozens of full-length cDNAs coding for proteins with sequence homology to snake venom prothrombin activator, trypsin-like enzymes, blood coagulation factors and prophenoloxidase cascade activators. We also report cDNA coding for cysteine proteases, Group III phospholipase A2, C-type lectins, lipocalins, in addition to protease inhibitors including serpins, Kazal-type inhibitors, cystatins and trypsin inhibitor-like molecules. Antibacterial proteins and housekeeping genes are also described. A significant number of sequences were devoid of database matches, suggesting that their biologic function remains to be defined. We also report the N-terminus of the most abundant proteins present in the bristle, tegument, hemolymph, and "cryosecretion". Thus, we have created a catalog that contains the predicted molecular weight, isoelectric point, accession number, and putative function for each selected molecule from the venomous structures of L. obliqua. The role of these molecules in the coagulation disorder and hemorrhagic syndrome caused by envenomation with this caterpillar is discussed. All sequence information and the , including figures and tables with hyperlinks to FASTA-formatted files for each contig and the best match to the databases, are available at http://www.ncbi.nih.gov/projects/omes. PMID:16023793

  13. Molecular cloning of the b subunit of mouse coagulation factor XIII and assignment of the gene to chromosome 1: Close evolutionary relationship to complement factor H

    Energy Technology Data Exchange (ETDEWEB)

    Nonaka, Mayumi; Nonaka, Masaru; Natsuume-Sakai, Shunnosuke (Kanazawa Univ. (Japan)); Matsuda, Yoichi (National Inst. of Radiological Science, Chiba (Japan)); Shiroishi, Toshihiko; Moriwaki, Kazuo (National Inst. of Genetics, Mishima (Japan))

    1993-03-01

    The b subunit of human coagulation factor XIII (FXIII-b) is composed of 10 short consensus repeats (SCRs) characteristic of the regulatory proteins of complement activation system. A full-length cDNA clone of mouse FXIII-b was isolated and the entire sequence was determined. The predicted amino acid sequence showed 77.5% homology with human FXIII-b, although mouse FXIII-b contained seven extra amino acid residues at the carboxyl terminal. The strong reactivity of the translation product of this clone with rabbit anti-human FXIII-b antiserum confirmed that it encodes a mouse counterpart of the human FXIII-b. By in situ hybridization and mapping studies using 66 interspecific backcross mice, the mouse FXIII-b gene (designated F13b) was shown to be located on distal chromosome 1 closely linked to Cfh, extending a conserved linkage group between human and mouse chromosome 1. In addition, a significant structural similarity between FXIII-b and complement factor H is described. 29 refs., 6 figs., 1 tab.

  14. 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...

  15. 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.

  16. Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors

    Czech Academy of Sciences Publication Activity Database

    Fajtová, P.; Štefanić, S.; Hradilek, M.; Dvořák, Jan; Vondrášek, J.; Jílková, A.; Ulrychová, L.; McKerrow, J.H.; Caffrey, C.R.; Mareš, M.; Horn, M.

    2015-01-01

    Roč. 9, č. 6 (2015), e0003827. ISSN 1935-2735 Institutional support: RVO:60077344 Keywords : Schistosoma mansoni * schistosomiasis * prolyl oligopeptidase * blood fluke Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.446, year: 2014

  17. 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

  18. 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

  19. 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.

  20. Understanding selectivity of hard and soft metal cations within biological systems using the subvalence concept. I. Application to blood coagulation: direct cation-protein electronic effects vs. indirect interactions through water networks

    Science.gov (United States)

    de Courcy, B.; Pedersen, L. G.; Parisel, O.; Gresh, N.; Silvi, B.; Pilmé, J.; Piquemal, J.-P.

    2010-01-01

    Following a previous study by de Courcy et al. ((2009) Interdiscip. Sci. Comput. Life Sci. 1, 55-60), we demonstrate in this contribution, using quantum chemistry, that metal cations exhibit a specific topological signature in the electron localization of their density interacting with ligands according to its “soft” or “hard” character. Introducing the concept of metal cation subvalence, we show that a metal cation can split its outer-shell density (the so-called subvalent domains or basins) according to it capability to form a partly covalent bond involving charge transfer. Such behaviour is investigated by means of several quantum chemical interpretative methods encompasing the topological analysis of the Electron Localization Function (ELF) and Bader's Quantum Theory of Atoms in Molecules (QTAIM) and two energy decomposition analyses (EDA), namely the Restricted Variational Space (RVS) and Constrained Space Orbital Variations (CSOV) approaches. Further rationalization is performed by computing ELF and QTAIM local properties such as electrostatic distributed moments and local chemical descriptors such as condensed Fukui Functions and dual descriptors. These reactivity indexes are computed within the ELF topological analysis in addition to QTAIM offering access to non atomic reactivity local index, for example on lone pairs. We apply this “subvalence” concept to study the cation selectivity in enzymes involved in blood coagulation (GLA domains of three coagulation factors). We show that the calcium ions are clearly able to form partially covalent charge transfer networks between the subdomain of the metal ion and the carboxylate oxygen lone pairs whereas magnesium does not have such ability. Our analysis also explains the different role of two groups (high affinity and low affinity cation binding sites) present in GLA domains. If the presence of Ca(II) is mandatory in the central “high affinity” region to conserve a proper folding and a charge

  1. 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.

  2. 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

  3. Interleukin-10 inhibits lipopolysaccharide-induced upregulation of tissue factor in canine peripheral blood monocytes.

    Science.gov (United States)

    Ogasawara, Seigo; Stokol, Tracy

    2012-08-15

    The potentially fatal hemostatic disorder of disseminated intravascular coagulation (DIC) is initiated in bacterial sepsis by lipopolysaccharide (LPS)-induced tissue factor (TF) expression on monocytes. Interleukin-10 (IL-10) is a potent inhibitory cytokine that downregulates monocyte inflammatory and procoagulant responses. We hypothesized that canine recombinant IL-10 (rIL-10) would inhibit LPS-induced TF upregulation on canine monocytes in a dose-dependent manner. Canine peripheral blood mononuclear cells (PBMC), obtained by double-density gradient centrifugation, and monocytes, purified from PBMC by immunomagnetic bead separation with an anti-canine CD14 antibody (Ab), were stimulated in suspension with LPS (0.1-1000 ng/mL) for various times. Recombinant IL-10 (10-5000 pg/mL) was added with LPS or up to 2h later. Tissue factor procoagulant activity was measured by cleavage of a chromogenic substrate by activated Factor X generated by the TF-factor VII complex. We found that rIL-10, when given concurrently or 1h after LPS, strongly inhibited LPS-induced TF procoagulant activity in canine PBMC and monocytes. This inhibition was dose-dependent and blocked by an anti-canine IL-10 Ab. Our results indicate that rIL-10 effectively inhibits LPS-induced TF upregulation in canine monocytes and could potentially be useful in limiting the development of DIC in dogs with endotoxemia. PMID:22609246

  4. 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.

  5. A serine protease inhibitor from hemolymph of green mussel, Perna viridis

    Digital Repository Service at National Institute of Oceanography (India)

    Khan, M.S.; Goswami, U.; Rojatkar, S.R.; Khan, M.I.

    of qua to respectively. that and innate immune mecha- memory following the first have is constituted perform ly, natural invertebrates, serine proteases and their inhibitors are also in- volved in parallel physiological processes, for example, the blood...- sin and are novel anticoagulants isolated from the marine animals. 5 In vertebrates, serine protease inhibitors have been studied extensively and they are known to be involved in phagocytosis, coagulation, complement activation, fibrinolysis, blood...

  6. 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

  7. No Evidence to Suggest that the Use of Acetylcholinesterase Inhibitors Confounds the Results of Two Blood-Based Biomarker Studies in Alzheimer's Disease

    OpenAIRE

    Chiam, Justin Tao Wen; Lunnon, Katie; Voyle, Nicola; Proitsi, Petroula; Coppola, Giovanni; Geschwind, Daniel,; Nelson, Sally; Johnston, Caroline; Soininen, Hilkka; Kłoszewska, Iwona; Mecocci, Patrizia; Tsolakik, Magda; Vellas, Bruno; Hodges, Angela; Lovestone, Simon

    2015-01-01

    Background: There is an urgent need to discover Alzheimer's disease (AD) biomarkers that are both easily measured and reliable. Research into blood-based biomarkers for AD using transcriptomics and proteomics has been an attractive and promising area of research. However, to date researchers have not looked into the possibility of AD medication being a confounding factor in these studies. Objective: This study explored whether acetylcholinesterase inhibitors (AChEIs), the main class of AD med...

  8. 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

  9. The estimation of metaloproteinases and their inhibitors blood levels in patients with pancreatic tumors

    OpenAIRE

    Śmigielski, Jacek; Piskorz, Łukasz; -Wojnarowska, Renata Talar; Malecka-Panas, Ewa; Jabłoński, Sławomir; Brocki, Marian

    2013-01-01

    Background The aim of the study was to evaluate the concentration of proteolytic enzymes, MMP-2 and MMP-9, and their tissue inhibitors, TIMP-1 and TIMP-2, in the blood of patients with benign and malignant pancreatic tumors. Methods MMP-2, MMP-9, TIMP-1, and TIMP-2 were evaluated in the patients with benign and malignant pancreatic tumors before surgery and in the 30-day follow-up. The study covered 134 patients aged 54 to 76 years, who were divided into groups by TNM staging. Results Before ...

  10. 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...

  11. Treatment with tumor necrosis factor inhibitors in axial spondyloarthritis

    DEFF Research Database (Denmark)

    Ciurea, A.; Weber, U.; Stekhoven, D.;

    2015-01-01

    -TNF agents in private practices in comparison to academic centers, adherence to ASAS treatment recommendations for TNF inhibition was equally high, and similar response rates to TNF blockers were achieved in both clinical settings. (First Release Nov 1 2014; J Rheumatol 2015; 42:101-5; doi 10.3899/jrheum......Objective. To evaluate the initiation of and response to tumor necrosis factor (TNF) inhibitors for axial spondyloarthritis (axSpA) in private rheumatology practices versus academic centers. The Journal of Rheumatology, Methods.We compared newly initiated TNF inhibition for axSpA in 363 patients...... enrolled in private practices with 100 patients recruited in 6 university hospitals within the Swiss Clinical Quality Management (SCQM) cohort., Results. All patients had been treated with > 1 nonsteroidal antiinflammatory drug and > 70% of patients had a baseline Bath Ankylosing Spondylitis Disease...

  12. 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.

  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. 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

    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....... The significant relationship is not associated with the -33T/C polymorphism, inflammation or endothelial cell perturbation, but is most likely related to release of tissue factor pathway inhibitor from fibrin deposits....

  15. Incidence and risk factors of occupational blood exposure

    DEFF Research Database (Denmark)

    Nelsing, S; Nielsen, T L; Brønnum-Hansen, Henrik;

    1997-01-01

    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......). 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...

  16. Coagulation testing in the perioperative period

    Directory of Open Access Journals (Sweden)

    Venkatesan Thiruvenkatarajan

    2014-01-01

    Full Text Available Perioperative coagulation management is a complex task that has a significant impact on the perioperative journey of patients. Anaesthesia providers play a critical role in the decision-making on transfusion and/or haemostatic therapy in the surgical setting. Various tests are available in identifying coagulation abnormalities in the perioperative period. While the rapidly available bedside haemoglobin measurements can guide the transfusion of red blood cells, blood product administration is guided by many in vivo and in vitro tests. The introduction of newer anticoagulant medications and the implementation of the modified in vivo coagulation cascade have given a new dimension to the field of perioperative transfusion medicine. A proper understanding of the application and interpretation of the coagulation tests is vital for a good perioperative outcome.

  17. 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...

  18. 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...

  19. 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

  20. Preanalytical conditions that affect coagulation testing, including hormonal status and therapy

    OpenAIRE

    BLOMBÄCK, M; Konkle, B A; Manco-Johnson, M. J.; Bremme, K.; HELLGREN, M; Kaaja, R.

    2007-01-01

    Preanalytical conditions, be they due to the individual's physiologic state or to exogenous factors, can affect coagulation factors, in either a transient or a persistent manner, and need to be considered in laboratory testing. These conditions include physical and mental stress, diurnal variation, hormone levels and posture at the time of blood drawing. While testing of these factors has not been exhaustive and some results are conflicting, guidelines for testing conditions can be given.

  1. Internal duplication and sequence homology in factors V and VIII.

    OpenAIRE

    Fass, D.N.; Hewick, R M; Knutson, G J; Nesheim, M. E.; Mann, K.G.

    1985-01-01

    Blood coagulation factors V and VIII each serve cofactor functions with different vitamin K-dependent serine proteases of the coagulation cascade. Physical, physiologic, and kinetic data suggest analogous structures and functions for these two proteins. Proteolytically activated factor V (factor Va) is required for the efficient production of thrombin from prothrombin by factor Xa. Similarly, activated factor VIII (factor VIIIa) performs its cofactor activity with factor IXa to produce the ac...

  2. Kinetic characterization of factor Xa binding using a quenched fluorescent substrate based on the reactive site of factor Xa inhibitor from Bauhinia ungulata seeds.

    Science.gov (United States)

    Oliva, M L V; Andrade, S A; Juliano, M A; Sallai, R C; Torquato, R J; Sampaio, M U; Pott, V J; Sampaio, C A M

    2003-07-01

    The specific Kunitz Bauhinia ungulata factor Xa inhibitor (BuXI) and the Bauhinia variegata trypsin inhibitor (BvTI) blocked the activity of trypsin, chymotrypsin, plasmin, plasma kallikrein and factor XIIa, and factor Xa inhibition was achieved only by BuXI (K(i) 14 nM). BuXI and BvTI are highly homologous (70%). The major differences are the methionine residues at BuXI reactive site, which are involved in the inhibition, since the oxidized protein no longer inhibits factor Xa but maintains the trypsin inhibition. Quenched fluorescent substrates based on the reactive site sequence of the inhibitors were synthesized and the kinetic parameters of the hydrolysis were determined using factor Xa and trypsin. The catalytic efficiency k(cat)/K(m) 4.3 x 10(7) M(-1)sec(>-1) for Abz-VMIAALPRTMFIQ-EDDnp (lead peptide) hydrolysis by factor Xa was 10(4)-fold higher than that of Boc-Ile-Glu-Gly-Arg-AMC, widely used as factor Xa substrate. Lengthening of the substrate changed its susceptibility to factor Xa hydrolysis. Both methionine residues in the substrate influence the binding to factor Xa. Serine replacement of threonine (P(1)') decreases the catalytic efficiency by four orders of magnitude. Factor Xa did not hydrolyze the substrate containing the reactive site sequence of BvTI, that inhibits trypsin inhibitor but not factor Xa. Abz-VMIAALPRTMFIQ-EDDnp prolonged both the prothrombin time and the activated partial thromboplastin time, and the other modified substrates used in this experiment altered blood-clotting assays. PMID:12678803

  3. Effect of Desmopressin on Platelet Aggregation and Blood Loss in Patients Undergoing Valvular Heart Surgery

    OpenAIRE

    Lei Jin; Hong-Wen Ji

    2015-01-01

    Background: Blood loss after cardiac surgery can be caused by impaired platelet (PLT) function after cardiopulmonary bypass. Desmopressin or 1-deamino-8-D-arginine vasopressin (DDAVP) is a synthetic analog of vasopressin. DDAVP can increase the level of von Willebrand factor and coagulation factor VIII, thus it may enhance PLT function and improve coagulation. In this study, we assessed the effects of DDAVP on PLT aggregation and blood loss in patients undergoing cardiac surgery. Methods:...

  4. Examining coagulation-complement crosstalk: complement activation and thrombosis.

    Science.gov (United States)

    Foley, Jonathan H

    2016-05-01

    The coagulation and complement systems are ancestrally related enzymatic cascades of the blood. Although their primary purposes have diverged over the past few hundred million years, they remain inextricably connected. Both complement and coagulation systems limit infection by pathogens through innate immune mechanisms. Recently, it has been shown that hyperactive complement (in particular, elevated C5a/C5b-9) is involved in the pathogenesis (including thrombosis) of diseases such as paroxysmal nocturnal hemoglobinuria, atypical haemolytic uremic syndrome, antiphospholipid syndrome and bacteremia. Although these diseases together account for many thrombosis cases, there are many more where complement activation is not considered a causative factor leading to thrombosis. To better understand what role complement may play in the pathogenesis of thrombosis a better understanding of the mechanisms that cause over-active complement in thrombotic disease is required. PMID:27207425

  5. 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

  6. 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.

  7. 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.

  8. 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...

  9. Effects of Paliperidone Palmitate on Coagulation: An Experimental Study

    Science.gov (United States)

    Yılmaz, Enver Demirel; Motor, Sedat; Pınar, Neslihan; Kokacya, Hanifi; Kisa, Mustafa; Oktar, Suleyman

    2014-01-01

    Objective. The aim of the present study was to examine the effects of a new antipsychotic drug paliperidone palmitate on hemogram and coagulation parameters in rats. Materials and Methods. Experiments were performed on 22 female albino Wistar rats (8–12 weeks old). Control group was given drinking water as vehicle (0.3 mL). PAL-1 rats were given 1 mg/kg paliperidone palmitate (in 0.3 mL drinking water) by oral gavage once a day for ten days and PAL-3 rats received 3 mg/kg paliperidone palmitate (in 0.3 mL drinking water) by oral gavage for ten days. Blood samples were drawn from the heart 24 hours after the last drug dose, and hemogram and coagulation parameters were measured with automated analyzers. Results. Hemogram did not change in the paliperidone treated groups compared to the controls. Factor VIII levels decreased in the PAL-1 and PAL-3 groups; and this decrease was significantly greater in the PAL-3. Factor IX levels decreased in PAL-3 rats, but its levels also increased in PAL-1 rats compared to the control. Discussion. Paliperidone has led to changes in the serum levels of coagulation factors VIII and IX in rats. As a result, paliperidone may be causing thromboembolism or bleeding in a dose-independent manner. PMID:24764772

  10. Effects of Paliperidone Palmitate on Coagulation: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Enver Demirel Yılmaz

    2014-01-01

    Full Text Available Objective. The aim of the present study was to examine the effects of a new antipsychotic drug paliperidone palmitate on hemogram and coagulation parameters in rats. Materials and Methods. Experiments were performed on 22 female albino Wistar rats (8–12 weeks old. Control group was given drinking water as vehicle (0.3 mL. PAL-1 rats were given 1 mg/kg paliperidone palmitate (in 0.3 mL drinking water by oral gavage once a day for ten days and PAL-3 rats received 3 mg/kg paliperidone palmitate (in 0.3 mL drinking water by oral gavage for ten days. Blood samples were drawn from the heart 24 hours after the last drug dose, and hemogram and coagulation parameters were measured with automated analyzers. Results. Hemogram did not change in the paliperidone treated groups compared to the controls. Factor VIII levels decreased in the PAL-1 and PAL-3 groups; and this decrease was significantly greater in the PAL-3. Factor IX levels decreased in PAL-3 rats, but its levels also increased in PAL-1 rats compared to the control. Discussion. Paliperidone has led to changes in the serum levels of coagulation factors VIII and IX in rats. As a result, paliperidone may be causing thromboembolism or bleeding in a dose-independent manner.

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

    Czech Academy of Sciences Publication Activity Database

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

    2012-01-01

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

  12. Inactivation of factor XII active fragment in normal plasma. Predominant role of C-1-inhibitor.

    Science.gov (United States)

    de Agostini, A; Lijnen, H R; Pixley, R A; Colman, R W; Schapira, M

    1984-06-01

    To define the factors responsible for the inactivation of the active fragment derived from Factor XII (Factor XIIf ) in plasma, we studied the inactivation kinetics of Factor XIIf in various purified and plasma mixtures. We also analyzed the formation of 125I-Factor XIIf -inhibitor complexes by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). In purified systems, the bimolecular rate constants for the reactions of Factor XIIf with C-1-inhibitor, alpha 2-antiplasmin, and antithrombin III were 18.5, 0.91, and 0.32 X 10(4) M-1 min-1, respectively. Furthermore, SDS-PAGE analysis revealed that 1:1 stoichiometric complexes were formed between 125I-Factor XIIf and each of these three inhibitors. In contrast, kinetic and SDS-PAGE studies indicated that Factor XIIf did not react with alpha 1-antitrypsin or alpha 2-macroglobulin. The inactivation rate constant of Factor XIIf by prekallikrein-deficient plasma was 14.4 X 10(-2) min-1, a value that was essentially identical to the value predicted from the studies in purified systems (15.5 X 10(-2) min-1). This constant was reduced to 1.8 X 10(-2) min-1 when Factor XIIf was inactivated by prekallikrein-deficient plasma that had been immunodepleted (less than 5%) of C-1-inhibitor. In addition, after inactivation in normal plasma, 74% of the active 125I-Factor XIIf was found to form a complex with C-1-inhibitor, whereas 26% of the enzyme formed complexes with alpha 2-antiplasmin and antithrombin III. Furthermore, 42% of the labeled enzyme was still complexed with C-1-inhibitor when 125I-Factor XII was inactivated in hereditary angioedema plasma that contained 32% of functional C-1-inhibitor. This study quantitatively demonstrates the dominant role of C-1-inhibitor in the inactivation of Factor XIIf in the plasma milieu. PMID:6725552

  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. 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

  15. 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

  16. Platelet Factor 4/Heparin Antibodies in Blood Bank Donors

    OpenAIRE

    Hursting, Marcie J; Pai, Poulomi J.; McCracken, Julianna E.; Hwang, Fred; Suvarna, Shayela; Lokhnygina, Yuliya; Bandarenko, Nicholas; Arepally, Gowthami M.

    2010-01-01

    Platelet factor 4 (PF4)/heparin antibody, typically associated with heparin therapy, is reported in some heparin-naive people. Seroprevalence in the general population, however, remains unclear. We prospectively evaluated PF4/heparin antibody in approximately 4,000 blood bank donors using a commercial enzyme-linked immunosorbent assay for initial and then repeated (confirmatory) testing. Antibody was detected initially in 249 (6.6%; 95% confidence interval [CI], 5.8%-7.4%) of 3,795 donors and...

  17. 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。

  18. 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

  19. 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.

  20. 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; Bak, Steffen; Valnickova, Zuzana; Thøgersen, Ida B; Jensen, Ole N; Højrup, Peter; Enghild, Jan J

    2011-01-01

    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. These...

  1. 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

  2. 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

  3. Whole-Blood Tissue Factor Procoagulant Activity Is Elevated in Type 1 Diabetes

    OpenAIRE

    Singh, Anamika; Boden, Guenther; Homko, Carol; Gunawardana, Jay; Rao, A. Koneti

    2012-01-01

    OBJECTIVE To determine tissue factor procoagulant activity (TF-PCA) in patients with type 1 diabetes and to examine effects of hyperglycemia and hyperglycemia plus hyperinsulinemia on TF-PCA. RESEARCH DESIGN AND METHODS We have determined circulating TF-PCA and other coagulation factors under basal (hyperglycemic) conditions, after acute correction of hyperglycemia, in response to 24 h of selective hyperglycemia, and in response to 24 h of hyperglycemia plus hyperinsulinemia in nine type 1 di...

  4. 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.

  5. 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

  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. Preoperative Factors Predicting Intraoperative Blood Loss in Female Patients With Adolescent Idiopathic Scoliosis

    Science.gov (United States)

    Li, Chao; Yang, Mingyuan; Wang, Chao; Wang, Chuanfeng; Fan, Jianping; Chen, Ziqiang; Wei, Xianzhao; Zhang, Guoyou; Bai, Yushu; Zhu, Xiaodong; Xie, Yang; Li, Ming

    2015-01-01

    Abstract In this article, a retrospective analysis of 161 female patients with adolescent idiopathic scoliosis (AIS) is performed who underwent posterior correction and fusion using all-pedicle screw instrument. The aim of this article is to find out preoperative factors that influence intraoperative blood loss (IOBL) in female patients with AIS. The IOBL in posterior correction and fusion surgery for patients with idiopathic scoliosis greatly varies. The variables affecting the IOBL also greatly vary among different studies. Medical records of all female patients with AIS who underwent posterior correction and fusion operations using the all-pedicle screw system in our hospital from January 2012 to January 2014 were reviewed. Patients with irregular menstruation, who underwent osteotomy, and using coagulants were excluded. Preoperative clinical data, including patient age, height, weight, Risser sign, day after last menstruation, major curve Cobb angle, fulcrum-bending Cobb angle, curve flexibility index, sagittal thoracic Cobb angle, sagittal lumbar Cobb angle, albumin, hemoglobin, platelet, activated partial thromboplastic time (APTT), prothrombin time, thrombin time, fibrinogen, fusion level, menstrual phase, and blood type, were collected. Data were further analyzed using multiple linear regression with forward elimination. A total of 161 patients were included in this study. The mean IOBL was 933.98 ± 158.10 mL (500–2000 mL). Forward selection showed that fulcrum-bending Cobb angle, fusion level, Risser sign, APTT, fibrinogen, and menstrual phase were the preoperative factors that influenced the IOBL in female patients with AIS. Equation of IOBL was built by multiple linear regression: IOBL = −966.228 + 54.738 Risser sign + 18.910 fulcrum-bending Cobb angle + 114.737 fibrinogen + 21.386 APTT − 71.312 team 2 − 177.985 team 3 − 165.082 team 4 + 53.470 fusion level. R = 0.782. Operation for patients with AIS was featured by large IOBL

  8. Avaliação de anticoagulantes naturais e de fatores da coagulação em pacientes com distúrbios congênitos de glicosilação (DCG tipo I An evaluation of natural anticoagulants and coagulation factors in patients with congenital disorders of glycosylation type I

    Directory of Open Access Journals (Sweden)

    Anna Letícia Soares

    2010-01-01

    with neurologic symptoms that include psychomotor retardation, ataxia, hypotonia and stroke-like episodes. Many haemostatic system proteins only present biological activity after glycosylation. The aim of this study was to evaluate coagulation inhibitors (free protein S, protein C and antithrombin and coagulation factors (VIII, IX and XI in CDG type I patients. Eleven patients with CDG type I (three males and eight females with a mean age of 5.6 years old, and eight patients without CDG (four males and four females with a mean age of 4.5 years old (control group were evaluated. The diagnoses of CDG type I were confirmed by isoelectric focusing of serum transferrin. When coagulation inhibitors were evaluated, decreased activity of free protein S and protein C, and a pronounced reduction of antithrombin were observed compared to the control group. There was no significant difference for coagulation factors VIII and IX but a markedly decrease in factor XI. The present results suggest that a combined deficiency of coagulation inhibitors is responsible for the pro-thrombotic state observed in CDG patients. We recommend that a haemostatic analysis should be performed in CDG patients with clinical haemostatic manifestations before invasive procedures are performed.

  9. 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...

  10. 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

  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. 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. 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.

  14. Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors

    Czech Academy of Sciences Publication Activity Database

    Fajtová, Pavla; Štefanic, S.; Hradilek, Martin; Dvořák, Jan; Vondrášek, Jiří; Jílková, Adéla; Ulrychová, Lenka; McKerrow, J. H.; Caffrey, C. R.; Mareš, Michael; Horn, Martin

    2015-01-01

    Roč. 9, č. 6 (2015), e0003827/1-e0003827/24. ISSN 1935-2735 R&D Projects: GA ČR(CZ) GAP302/11/1481; GA MŠk LO1302 Institutional support: RVO:61388963 ; RVO:68378050 Keywords : Schistosoma mansoni * schistosomiasis * prolyl oligopeptidase * blood fluke Subject RIV: CE - Biochemistry; EB - Genetics ; Molecular Biology (UMG-J) Impact factor: 4.446, year: 2014 http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003827

  15. 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

  16. Cartilage oligomeric matrix protein is a natural inhibitor of thrombin.

    Science.gov (United States)

    Liang, Ying; Fu, Yi; Qi, Ruomei; Wang, Meili; Yang, Nan; He, Li; Yu, Fang; Zhang, Jian; Yun, Cai-Hong; Wang, Xian; Liu, Junling; Kong, Wei

    2015-08-13

    Thrombin is an effector enzyme for hemostasis and thrombosis; however, endogenous regulators of thrombin remain elusive. Cartilage oligomeric matrix protein (COMP), a matricellular protein also known as thrombospondin-5, is essential for maintaining vascular homeostasis. Here, we asked whether COMP is involved in the process of blood coagulation. COMP deficiency shortened tail-bleeding and clotting time and accelerated ferric-chloride-induced thrombosis in mice. The absence of COMP had no effect on platelet count. In contrast, COMP specifically inhibited thrombin-induced platelet aggregation, activation, and retraction and the thrombin-mediated cleavage of fibrinogen. Furthermore, surface plasmon resonance analysis revealed direct thrombin-COMP binding (KD = 1.38 ± 0.24 μM). In particular, blockage of thrombin exosites with compounds specific for exosite I (hirudin and HD1 aptamer) or exosite II (heparin and HD22 aptamer) impaired the COMP-thrombin interaction, indicating a 2-site binding mechanism. Additionally, epidermal growth factor-like repeats (amino acids 84-261) were identified as a COMP binding site for thrombin. Moreover, COMP was expressed in and secreted by platelets. Using bone marrow transplantation and platelet transfusion to create chimeric mice, platelet-derived but not vessel-wall-derived COMP was demonstrated to inhibit coagulation. Taken together, COMP is an endogenous thrombin inhibitor and negative regulator of hemostasis and thrombosis. PMID:26045608

  17. 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.

  18. 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

  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. 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

  1. 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

  2. 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

  3. 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

  4. 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

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

    OpenAIRE

    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 combi...

  6. Dust coagulation in ISM

    Science.gov (United States)

    Chokshi, Arati; Tielens, Alexander G. G. M.; Hollenbach, David

    1989-01-01

    Coagulation is an important mechanism in the growth of interstellar and interplanetary dust particles. The microphysics of the coagulation process was theoretically analyzed as a function of the physical properties of the coagulating grains, i.e., their size, relative velocities, temperature, elastic properties, and the van der Waal interaction. Numerical calculations of collisions between linear chains provide the wave energy in individual particles and the spectrum of the mechanical vibrations set up in colliding particles. Sticking probabilities are then calculated using simple estimates for elastic deformation energies and for the attenuation of the wave energy due to absorption and scattering processes.

  7. Allelic ladder characterization of the short tandem repeat polymorphism located in the 5{prime} flanking region to the human coagulation factor XIII A subunit gene

    Energy Technology Data Exchange (ETDEWEB)

    Puers, C. [Promega Corp., Madison, WI (United States)]|[Institute for Forensic Medicine, Muenster (Germany); Lins, A.M.; Sprecher, C.J. [Promega Corp., Madison, WI (United States)] [and others

    1994-09-01

    The short tandem repeat (STR) polymorphism present within the 5{prime} untranslated region of the human coagulation factor XIII A subunit gene, HUM-F13A01 [AAAG]{sub n}, was evaluated using an allelic ladder, i.e., a standard size marker consisting of amplified alleles from the locus. The allelic ladder was constructed by pooling 12 polymerase chain reaction (PCR)-amplified alleles identified by their differential migration in denaturing polyacrylamide gel electrophoresis. This standard marker was used to distinguish 14 different alleles observed at this locus. Sequence analyses indicate that 13 of the alleles contain 4 through 16 iterations of the tandemly repeated AAAG sequence, respectively. The remaining allele carries four repeats and displays a deletion of two consecutive nucleotides (GT), one base distal to the repeat region. The allelic ladder was employed to type 326 F13A01 chromosomes rapidly and reliably in representatives of a German Caucasian population. Population data were analyzed with respect to Hardy-Weinberg Equilibrium (HWE) and compared with those of a previously studied Houston, Texas, Caucasian population. 27 refs., 2 figs., 1 tab.

  8. 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

  9. 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

  10. Disseminated intravascular coagulation following administration of sunitinib

    Science.gov (United States)

    OLIVO, ANAËLLE; NOËL, NICOLAS; BESSE, BENJAMIN; TABURET, ANNE-MARIE; LAMBOTTE, OLIVIER

    2016-01-01

    Sunitinib is an increasingly used, orally administered targeted therapy, approved by the European Medicines Agency for the treatment of various types of cancer, including gastrointestinal stromal tumor unresectable or metastatic disease, following disease progression or intolerance to imatinib, and advanced or metastatic renal cell carcinoma, progressive well-differentiated pancreatic neuroendocrine tumors in patients with unresectable, locally advanced or metastatic disease. Sunitinib inhibits several tyrosine kinases, including the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor. Tyrosine kinases inhibitor therapies are generally well-tolerated; nonetheless, they are not void of side effects. The majority of patients reported are grade 1 or 2, and include common and unspecific adverse events, including fatigue, gastrointestinal disorders, skin discoloration, altered taste, cough and dyspnea. Grade 3 or 4 adverse events, including bleeding and hemorrhage, are less frequent. The present study presented the first case of disseminated intravascular coagulation associated with the administration of sunitinib, shortly following the increase of sunitinib dosage. PMID:27330781

  11. 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

  12. 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 recalcification time(P < 0.001).Petroleum ether extract of the bracts significantly prolonged the plasma recalcification time (P < 0.001).The results indicated that the n-butanol extract of bars and bract ethyl acetate extract had better procoagulant effect,and the petroleum ether extract of the bracts had good anticoagulant effect.%采用体外血浆复钙时间法,以维生素k1作为促凝血和灯盏花素作为抗凝血作用阳性对照,对玉蜀黍轴及苞叶石油醚、乙酸乙酯和正丁醇提取物及玉蜀黍苞叶甲醇总浸膏对体外血浆复钙时间的影响进行测定.结果显示玉蜀黍轴正丁醇及苞叶乙酸乙酯提取物,均可显著缩短体外血浆复钙时间(P<0.001);玉蜀黍苞叶石油醚提取物可显著延长体外血浆复钙时间(P<0.001).提示玉蜀黍轴正丁醇及苞叶乙酸乙酯提取物具有较好的促凝血活性,玉蜀黍苞叶石油醚提取物具有较好的抗凝作用.

  13. 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.

  14. 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

  15. Reduction of Risk Factor Coagulation Oxidative Apolipoprotein and Development of Atherosclerosis by Apple Cider Vinegar in Hypercholesterolemic Rabbits

    Directory of Open Access Journals (Sweden)

    Mahbubeh Setorki

    2009-01-01

    Full Text Available Introduction: Apple cider vinegar is an antioxidant compound and it has many medical uses. In this research we have investigated effects of apple cider vinegar on some risk factors of atherosclerosis and on the development of atherosclerosis in hypercholesterolemic rabbit. Methods: Thirty two male New Zealand rabbits were randomly divided into four groups: normal diet group high cholesterol diet group (%1cholesterol %1 cholesterol with 5ml apple cider vinegar group and %1 cholesterol with 10ml apple cider vinegar group .The malondialdehyde (MDA oxidized-LDL (oxLDL fibrinogen factor VII apolipoprotein A (ApoA and apolipoprotein B (ApoB were measured before the experiment and at the end period (2month. At the end of study using Chekanov method fatty streak formation in aorta artery was determined in all groups. Results: Using both doses of apple cider vinegar significantly decreased fibrinogen oxLDL MDA ApoB ApoB/ApoA VIIlevels in comparison with hypercholesterolemic diet (P0.05. Also consumption of apple cider vinegar induced significant decrease in atherosclerotic lesions in aorta artery compared to the hypercholesterolemic diet. Conclusion: This study suggests that apple cider vinegar (as an antioxidant might have some protective effects on biochemical risk factors of atherosclerosis.

  16. Alterations in coagulation following major liver resection.

    Science.gov (United States)

    Mallett, S V; Sugavanam, A; Krzanicki, D A; Patel, S; Broomhead, R H; Davidson, B R; Riddell, A; Gatt, A; Chowdary, P

    2016-06-01

    The international normalised ratio is frequently raised in patients who have undergone major liver resection, and is assumed to represent a potential bleeding risk. However, these patients have an increased risk of venous thromboembolic events, despite conventional coagulation tests indicating hypocoagulability. This prospective, observational study of patients undergoing major hepatic resection analysed the serial changes in coagulation in the early postoperative period. Thrombin generation parameters and viscoelastic tests of coagulation (thromboelastometry) remained within normal ranges throughout the study period. Levels of the procoagulant factors II, V, VII and X initially fell, but V and X returned to or exceeded normal range by postoperative day five. Levels of factor VIII and Von Willebrand factor were significantly elevated from postoperative day one (p < 0.01). Levels of the anticoagulants, protein C and antithrombin remained significantly depressed on postoperative day five (p = 0.01). Overall, the imbalance between pro- and anticoagulant factors suggested a prothrombotic environment in the early postoperative period. PMID:27030945

  17. Coagulation properties of milk

    OpenAIRE

    Hallén, Elin

    2008-01-01

    Concentrations of the different proteins in milk are important for the outcome of the coagulation processes which yield our dairy products, whereas total milk protein content is a poor indicator of coagulation properties of milk. In order to design the milk protein composition to meet dairy processing requirements, selection for genetic variants of milk proteins have been proposed. This work aimed to study genetic milk protein polymorphism and its association with the detailed milk protein co...

  18. Coagulation and Mental Disorders

    Directory of Open Access Journals (Sweden)

    Silvia Hoirisch-Clapauch

    2014-10-01

    Full Text Available The neurovascular unit is a key player in brain development, homeostasis, and pathology. Mental stress affects coagulation, while severe mental illnesses, such as recurrent depression and schizophrenia, are associated with an increased thrombotic risk and cardiovascular morbidity. Evidence indicates that the hemostatic system is involved to some extent in the pathogenesis, morbidity, and prognosis of a wide variety of psychiatric disorders. The current review focuses on emerging data linking coagulation and some psychiatric disorders.

  19. 中国市场人凝血因子Ⅷ质量分析%Assessment of human coagulation factor Ⅷ in the Chinese market

    Institute of Scientific and Technical Information of China (English)

    张学俊; 叶生亮; 杜晞; 谢亦武; 曹海军; 王宗奎; 李长清

    2012-01-01

    Objective To study these human coagulation FⅧ products in China,a preliminary analysis is made on the active ingredients as well as impurity profile. The research on these factor Ⅷ products' efficacy and safety serves to establish new standards for product quality and provide some theoretical basis for applications. Methods A S Corp' s human F Ⅶ .Cross' F Ⅷ.CSL' s Aleviate,L Corp' s F Ⅷ and Bayer' s Kogenate(R) FS are evaluated through the determination of F Ⅲ,F V,F Ⅵ,F Ⅸ,FX and F Ⅷ clotting capability, as well as preliminary evaluation of vWF activity content. Non-reducing and reducing SDS-PAGE electrophoresis is employed to assess purity,while protein content is determined by three different assays. Results The results in the clotting activity,protein concentration and purity indicate that there are qualitative differences among these factor Ⅷ products. Conclusion Preparation by different processes may lead to different product quality Qualitative evaluation of coagulation factor products may be influenced by different methods, equipment and test kits employed. Glycine affect the results of Bradford total protein content determination. The present study show one of the key quality parameters of FⅧ - specific activity in these products to be greater than the WHO requirements for a high-purity FⅧ (10IU/mg) as well as the Chinese Pharmacopoeia 2010 (1IU/mg) requirements.%目的 考察了5种、11个批次的中国市场人凝血因子Ⅷ(FⅧ)制品,分析相关制品的成份.研究对国内制品的有效性和安全性做出评估,为建立新的制品质量标准提供理论依据.方法 选用S公司人FⅦ、CSL Aleviate、+公司人FⅧ、L公司人FⅧ和Bayer Kogenate(@)FS,通过FⅧ测定进行制品活性评估,通过FⅡ、FⅤ、FⅦ、FⅨ、FⅩ分析杂质蛋白含量,用3种不同蛋白测定方法测定制品总蛋白含量;初步评价von Willebrand Factor(vWF)活性,并用非还原和还

  20. 不同年龄发绀型先心病患儿围体外循环期凝血功能的比较%Changes in blood coagulation during cardiopulmonary bypass in children of different ages with cyanotic congenital heart disease

    Institute of Scientific and Technical Information of China (English)

    陈煜; 黄延辉; 白洁

    2010-01-01

    Objective To investigate the changes in blood coagulation during cardiopulmonary bypass (CPB) in children of different ages undergoing open heart surgery for cyanotic congenital heart disease.Methods Sixty children with cyanotic congenital heart disease undergoing open heart surgery under CPB were divided into 3 age groups: Group A(age≤12 mort, n=25), Group B (12mon<age≤24 mon, n= 17) and Group C (24 mon< age<4 yr, n=18). Venous blood samples were taken immediately after induction of anesthesia(T1) and at 10 min after protamine administration (T2)for determination of activated coagulation time (SonACT), clot rate and platelet function (PF) using Sonoclot coagulation and platelet function analyzer-type DP2951 (Sieuco Co., USA).Results There was significant difference in SonACT, clot rate and PF at T1 among the 3 groups: the SonACT was significantly shorter in Groups B and C than in Group A, the clot rate was significantly higher in Group B than in Group C, and the PF was significantly lower in Group C than in Group A. At T2 , the SonACT was significantly prolonged in all 3 groups, the clot rate was significantly decreased in Groups A and B, and the PF was significantly decreased in Group A.Conclusion There are significant differences in blood coagulation and PF among the 3 different age groups of children with cyanotic congenital heart disease after induction of anesthesia and CPB has different effects on their blood coagulation and PF.

  1. Coagulation function in patients with pancreatic carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Hang-yan; XIU Dian-rong; LI Zhi-fei; WANG Gang

    2009-01-01

    Background The coagulation function in patients with pancreatic carcinoma is abnormal and the reason is not very clear. In this study, we retrospectively analyzed the coagulation function in patients with pancreatic carcinoma.Methods From June 2004 to December 2007, 132 patients received diagnosis and treatment in our hospital. The coagulative parameters including the prothrombin time, activated partial thromboplastin time, and fibrinogen levels were collected and studied retrospectively.Results The average fibrinogen levels in patients with pancreatic carcinoma, (476.21±142.05) mg/dl, were significantly higher than in patients with cholangiolithiasis, (403.28±126.41) mg/dl (P 0.05).Conclusions The level of fibrinogen in patients with pancreatic carcinoma was elevated. The elevated fibrinogen level may be associated with invasiveness and lymphatic metastasis. Using vitamin K in perioperation management did not reduce intraoperative blood loss.

  2. Von Willebrand factor-containing factor VIII concentrates and inhibitors in haemophilia A. A critical literature review.

    Science.gov (United States)

    Franchini, Massimo; Lippi, Giuseppe

    2010-11-01

    The development of inhibitors that neutralise the function of factor VIII (FVIII) is currently not only the most challenging complication associated with the treatment of haemophilia A but it also increases the disease-related morbidity as bleeding episodes do not respond to standard therapy. The main short-term goal of the treatment of inhibitor patients is to control bleeding episodes while the long-term one is to permanently eradicate the inhibitor by immune tolerance induction, particularly in the case of high-titer antibodies. Due to some in vitro studies and clinical observations, some investigators have suggested that FVIII concentrates containing von Willebrand factor (VWF) may be less immunogenic than high-purity or recombinant FVIII products. It has also been suggested that success rates for immune tolerance induction are higher when plasma-derived FVIII products are used. The currently available data from laboratory and clinical studies on the role of VWF in inhibitor development and eradication in haemophilia A is critically analysed in this review. As a result, we have not found definitive evidence supporting a role for product type on inhibitor incidence and inhibitor eradication in haemophilia A patients. PMID:20838738

  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. 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

  5. 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.

  6. Perioperative changes in coagulative and fibrinolytic function during surgical treatment of abdominal aortic aneurysm and arteriosclerosis obliterans.

    Science.gov (United States)

    Aramoto, H; Shigematsu, H; Muto, T

    1994-12-01

    To determine the factors which influence perioperative coagulative and fibrinolytic function, we studied 41 patients who underwent surgical repair of unruptured abdominal aortic aneurysm (AAA) and 30 patients who underwent arterial reconstruction for arteriosclerosis obliterans (ASO). In patients with AAA, the levels of fibrin/fibrinogen degradation products (FDP) (11.4 +/- 20.1 micrograms/ml), thrombin-antithrombin III complex (TAT) (22.0 +/- 21.8 micrograms/l), plasmin-alpha 2 plasmin inhibitor complex (PIC) (2.6 +/- 2.9 micrograms/ml) and d-dimer of cross-linked fibrin degradation products (D-D) (8.4 +/- 10.8 micrograms/ml) were elevated, particularly when the AAAs had a large mural thrombus surface area or were accompanied by aneurysm of the iliac or femoral artery. In arterial aneurysms, blood coagulability and secondary fibrinolytic activity were believed to be enhanced. In patients with ASO, the level of TAT (17.2 +/- 24.8 micrograms/l) was so elevated that they were considered to show chronic hypercoagulability. Among the ASO patients with aorto-iliac lesions, those with concomitant graft occlusion or anastomotic aneurysm had significantly elevated levels of TAT. Proximal arterial occlusion or accompanying aneurysm in the ASO patients was associated with increased levels of PIC and D-D. Postoperative fluctuations in conventional hematological variables did not differ significantly among the surgical procedures. Conventional markers showed a transient decrease due to consumption during surgery, and a subsequent recovery or an actual increase within several days after surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7737753

  7. 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

  8. SYSMEX CS 5100全自动血凝分析仪的性能评价%Evaluation on the performance of Sysmex CS 5100 automatic blood coagulation analyzer

    Institute of Scientific and Technical Information of China (English)

    王芳; 张军; 徐唯傑; 乐军; 陈晓燕; 陈晋

    2015-01-01

    目的:对Sysmex CS 5100(下简称CS 5100)全自动血凝仪进行性能评价。方法对CS 5100血凝仪的准确性、不精密度、Fg 线性(可报告范围)、参考范围、携带污染率进行评价,并与 Sysmex 公司生产的 CA 7000全自动血凝分析仪进行相关性试验,所测指标为 PT、PT(INR)、APTT、Fbg、TT、AT、D 二聚体(DD)和 FDP。结果准确性试验测定结果在质控说明书给定的范围内。批内最大变异系数(CV)与日间最大 CV 均符合符合相关行业文件要求。Fbg 线性验证试验结果显示 Fbg 线性范围为1.071~5.355,相关系数(r)值为0.9950,符合规定要求(r≥0.975)。参考范围验证试验结果显示各项检测指标 R 值均>0.9,实验室预设参考范围可适用于该仪器。CS 5100与 CA 7000的各项检测项目 r 值均>0.95,两仪器结果有很好的对比性。结论CS 5100有优异的准确性、精密度良好、Fbg 检测范围宽、抗生物干扰能力强,完全可满足临床实验室要求。%Objective To evaluate the performance of Sysmex CS 51 00 automatic blood coagulation analyzer. Methods PT,PT(INR),APTT,Fbg,TT,AT,D-dimer (DD)and FDP were measured by Sysmex CS 51 00 automatic blood coagulation analyzer.The accuracy,imprecision,Fg linearity (reportable range),reference range, carry-over rate were evaluated,and the correlation with Sysmex CA 7000 automatic blood coagulation analyzer was analyzed.Results The accuracy was in the range provided by quality control instructions.The maximum within-run and inter-day coefficients of variation met the requirements of Clia′88.Fbg linear validation test showed that the linearity of Fbg was from 1 .071 to 5.355,and the correlation coefficient (r)was 0.9950,which met the specified requirements (r≥0.975).The reference range verification tests showed that the R values of all the tests were >0.9,which proved that the laboratory preset reference range can be

  9. 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

  10. 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; Olesen, Jes

    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, and...... repeatedly. Headache responses and tenderness of pericranial muscles were scored verbally. Sildenafil caused no significant changes in rCBFmca, Vmca, or in temporal or radial artery diameter, but heart rate increased and diastolic blood pressure decreased significantly compared to placebo. Despite the lack...

  11. 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 K; Havemose-Poulsen, Anne; 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......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.......001) or JIA (P = 0.002), and PBMC TNFA transcript levels were lower in patients with JIA (P = 0.001). A negative correlation was found between IL6 expression and IL-6 plasma levels in patients with JIA versus controls, and a positive correlation/association was found between TNFRI expression and s......TNF-RI plasma levels in patients with LAgP and RA. CONCLUSIONS: The study demonstrated only a few changes in the PBMC expression of various cytokine and cytokine inhibitor genes in aggressive periodontitis and chronic arthritis compared to controls. There were a few similarities among disease groups, and no...

  12. Variation of Sensitive Blood Coagulation Indexes in Infants with Hemorrhagic Disease of the Newborn Treated with Vitamin K%维生素 K治疗新生儿出血症凝血指标的变化

    Institute of Scientific and Technical Information of China (English)

    明静

    2014-01-01

    目的:评价维生素K治疗新生儿出血症( HDN)对凝血指标的影响。方法在维生素K治疗前后分别检测37例HDN患儿凝血酶原前体蛋白( PIVKA-Ⅱ)、凝血酶原时间( PT)、部分活化凝血活酶时间( APTT)、凝血酶原活动度( PTA)、凝血酶时间( TT)及纤维蛋白原( FIB)。结果维生素K治疗后凝血指标PIVKA-Ⅱ、PT明显降低(P<0.05),PTA、APTT明显升高(P<0.05),维生素K治疗后凝血指标PIVKA-Ⅱ、PTA、PT、APTT异常率较治疗前明显降低( P<0.05)。而TT、FIB异常率未出现明显变化( P>0.05)。结论 HDN患儿在使用维生素K治疗后,PIVKA-Ⅱ、PTA、PT、APTT变化明显,反应敏感,能较好地反映HDN的凝血水平,可作为HDN的诊断依据及转归指标。%Objective To evaluate the effect of Vitamin K on blood coagulation indexes in infants with hemorrhagic disease of the newborn(HDN).Methods Thirty-seven cases of HDN were meausred for protein induced by Vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ),prothrombin time(PT),activated partial thromboplastin time (APTT),prothrombin time activity(PTA),thrombin time(TT),human fibrinogen(FIB) before and after treatment of Vitamin K.Results PIVKA-Ⅱ, PT decreased significantly after treatment of Vitamin K (P0.05).Conclusion PIVKA-Ⅱ, PT,APTT,and PTA have improved significantly after the treatment of Vitamin K in infants with HDN ,which can reflect the blood coagulation level .They can be applied to the diagnosis and prognosis of HDN .

  13. The impact of statins for the network between blood coagulation and inflammation in sepsis%他汀类调脂药物对脓毒症凝血-炎症网络的影响

    Institute of Scientific and Technical Information of China (English)

    黎永琳; 周红

    2014-01-01

    Sepsis is a systemic inflammatory response syndrome by infection , which can develop into severe sepsis or sepsis shock.The case fatality rate is still 30%~70%, although with the evolutive anti-inflective therapy and multi-organ support therapy.It was found that lipid metabolism was chaotic in sepsis in some recent studies. Stains are known for reducing blood lipid and improving the atherosclerosis, but they are also noted by improving inflammation, coagulation,endothelial function and so on in sepsis.This paper will introduce the impact of statins for the network between blood coagulation and inflammation in sepsis.%目的脓毒症是由于感染引起的全身系统性炎症反应,可发展为严重脓毒症和感染性休克。尽管抗感染治疗和器官功能支持技术取得了长足的进步,脓毒症的病死率仍高达30%~70%。近年来的研究表明,脓毒症发生时,脂质代谢同样发生紊乱。他汀类药物因为其能有效地降低血脂,改善动脉粥样硬化情况而被大家所认识。随着对该药物的进一步研究发现,他汀类药物降脂以外的作用越来越受到重视,如改善内皮功能、抑制血管炎症、改善凝血功能、减少血栓形成和改善总体血管功能等。本文就目前他汀类药物治疗脓毒症时抗炎、抗凝影响的研究做一简述。

  14. Influence of coagulation factor x on in vitro and in vivo gene delivery by adenovirus (Ad) 5, Ad35, and chimeric Ad5/Ad35 vectors.

    Science.gov (United States)

    Greig, Jenny A; Buckley, Suzanne Mk; Waddington, Simon N; Parker, Alan L; Bhella, David; Pink, Rebecca; Rahim, Ahad A; Morita, Takashi; Nicklin, Stuart A; McVey, John H; Baker, Andrew H

    2009-10-01

    The binding of coagulation factor X (FX) to the hexon of adenovirus (Ad) 5 is pivotal for hepatocyte transduction. However, vectors based on Ad35, a subspecies B Ad, are in development for cancer gene therapy, as Ad35 utilizes CD46 (which is upregulated in many cancers) for transduction. We investigated whether interaction of Ad35 with FX influenced vector tropism using Ad5, Ad35, and Ad5/Ad35 chimeras: Ad5/fiber(f)35, Ad5/penton(p)35/f35, and Ad35/f5. Surface plasmon resonance (SPR) revealed that Ad35 and Ad35/f5 bound FX with approximately tenfold lower affinities than Ad5 hexon-containing viruses, and electron cryomicroscopy (cryo-EM) demonstrated a direct Ad35 hexon:FX interaction. The presence of physiological levels of FX significantly inhibited transduction of vectors containing Ad35 fibers (Ad5/f35, Ad5/p35/f35, and Ad35) in CD46-positive cells. Vectors were intravenously administered to CD46 transgenic mice in the presence and absence of FX-binding protein (X-bp), resulting in reduced liver accumulation for all vectors. Moreover, Ad5/f35 and Ad5/p35/f35 efficiently accumulated in the lung, whereas Ad5 demonstrated poor lung targeting. Additionally, X-bp significantly reduced lung genome accumulation for Ad5/f35 and Ad5/p35/f35, whereas Ad35 was significantly enhanced. In summary, vectors based on the full Ad35 serotype will be useful vectors for selective gene transfer via CD46 due to a weaker FX interaction compared to Ad5. PMID:19603000

  15. Dermatological side effects of epidermal growth factor receptor inhibitors: ′Pride′ complex

    Directory of Open Access Journals (Sweden)

    Bhushan Madke

    2014-01-01

    Full Text Available Epidermal growth factor receptor (EGFR inhibitor therapy has become the standard treatment for non-small cell lung cancer and head neck malignancy. This class of drug comprises EGFR inhibitors (erlotinib and gefitinib and monoclonal antibody (cetuximab. Use of this class of drugs has been associated frequently with dermatological side effects termed as PRIDE complex-Papulopustules and/ or paronychia, Regulatory abnormalities of hair growth, Itching, Dryness due to EGFR inhibitors. We hereby report the cutaneous side effects of EGFR inhibitor therapy in 15 patients of lung and head/neck cancer. The major clinical findings being acneiform eruption and severe xerosis of skin. Management of these dermatological adverse effects rarely requires discontinuation of targeted therapy and can be managed symptomatically.

  16. “ STUDY OF COAGULATION PROFILE IN CLINICALLY DIAGNOSED CASES OF ACUTE DISSEMINATED INTRAVASCULAR COAGULATION USING ISTH CRITERIA

    Directory of Open Access Journals (Sweden)

    Chopade

    2013-10-01

    Full Text Available Disseminated Intravascular Coagulation (DIC is a pathological activation of coagulation (blood clotting mechanisms that happens in response to a variety of diseases. It involves the generation of intravascular fibrin (small blood c lots and the consumption of pro - coagulants and platelets. It results in the disruption of normal coagulation mechanism and abnormal bleeding occurs from the skin, the gastrointestinal tract, the respiratory tract and surgical wounds. It was the prospecti ve study of 60 patients of acute DIC, in which coagulation profile were studied from December 2010 to October 2012 . 40 controls were studied. Control group include healthy voluntary blood donors. The coagulation profile was studied and DIC scoring was p erformed using the International Society on Thrombosis and Haemostasis [ISTH] criteria. Among the coagulation profile, the sensitivity and specificity of the parameters to diagnose and to assess the severity of DIC, in the decreasing order of frequency wer e of platelet count, D - dimer, PT and APTT. Fibrinogen level was not depleted below the significant level (<1 gm/l in majority cases of DIC. According to the ISTH criteria, DIC scores among cases was ≥ 5.

  17. Gene therapy for hemophilia B mediated by recombinant adeno-associated viral vector with hFIXR338A, a high catalytic activity mutation of human coagulation factor IX

    Institute of Scientific and Technical Information of China (English)

    LU; Huazhong; (

    2001-01-01

    [1]Chang, J., Jin, J., Lollar, P. et al., Changing residue 338 in human factor IX from arginine to alanine causes an increase in catalytic activity, J. Bio. Chem., 1998, 273 (20): 12089-12094.[2]Lai, L., Chen, L., Zhou, H. et al., Clinical phenotype and genetic stability of factor IX gene knock out mice, J. Fudan Uni., 1999, 38 (4): 435-438.[3]Wu, Z. J., Wu, X. B., Hou, Y. D., Generation of a recombinant herps simplex virus which can provide packaging function for recombinant adeno-associated virus, Chinese Sci. Bull., 1999, 44 (8): 715-719.[4]Snyder, R. O., Miao, C. H., Patijn, G. A. et al., Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer of recombinant AAV vectors, Nat. Genet., 1997, 16 (3): 270-276.[5]Lai, L. H., Chen, L., Wang, J. M. et al., Skeletal muscle-specific expression of human blood coagulation factor IX rescues factor IX deficiency mouse by AAV-mediated gene transfer, Science in China, Ser. C, 1999, 42 (6): 628-634.[6]Snyder, R. O., Miao, C., Meuse, L. et al., Correction of hemophilia B in canine and murine models using recombinant adeno-associated viral vectors, Nat. Med., 1999, 5 (1): 64-70.[7]Kung, S. H., Hagstrom, J. N., Cass, D. et al., Human factor IX corrects the bleeding diathesis of mice with hemophilia B, Blood, 1998, 91(3): 784-790.[8]Hirt, B., Selective extraction of polyoma DNA from infected mouse cell culture, J. Mol. Biol., 1967, 26: 365-369.[9]Sambrook, J., Fritsch, E., Maniatis, T., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Laboratory Press, 1989, 6, 20-21.[10]Chao, H., Samulski, R. J., Bellinger, D. A. et al., Persistent expression of canine factor IX in hemophilia B canines, Gene Ther., 1999, 6: 1695-1704.[11]Kaufman, R. J., Advances toward gene therapy for hemophilia at the millennium, Hum. Gene Ther., 1999, 10 (13): 2091-2107.[12]Lu, D. R., Zhou, J. M., Zheng, B. et al., Stage I clinical trial of gene

  18. 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.

  19. Microbes Bind Complement Inhibitor Factor H via a Common Site

    OpenAIRE

    Meri, T.; Amdahl, H.; Lehtinen, M. J.; Hyvärinen, S.; McDowell, J.V.; Bhattacharjee, A.; Meri, S.; Marconi, R.; Goldman, A; Jokiranta, T. S.

    2013-01-01

    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 ...

  20. Risk Factors and Screening for Trypanosoma cruzi Infection of Dutch Blood Donors

    OpenAIRE

    Slot, Ed; Hogema, Boris M; Molier, Michel; BART, Aldert; Hans L Zaaijer

    2016-01-01

    Background Blood donors unaware of Trypanosoma cruzi infection may donate infectious blood. Risk factors and the presence of T. cruzi antibodies in at-risk Dutch blood donors were studied to assess whether specific blood safety measures are warranted in the Netherlands. Methodology Birth in a country endemic for Chagas disease (CEC), having a mother born in a CEC, or having resided for at least six continuous months in a CEC were considered risk factors for T. cruzi infection. From March thro...

  1. IMPROVEMENT OF COAGULATION PROCESS FOR THE PRUT RIVER WATER TREATMENT USING ALUMINUM SULPHATE

    Directory of Open Access Journals (Sweden)

    Larisa Postolachi

    2015-06-01

    Full Text Available The aim of presented research was to optimize the treatment process of the Prut River water. In order to realize the proposed goal, there were studied the following factors which can improve the process of coagulation: (i the influence of stirring speed during coagulation and (ii the influence of the concentration of the coagulant solution added in the process of coagulation. The optimal conditions of coagulation were established using the Jar-test method. Application of the recommended procedure contribute to the reduction of the coagulant dose, the contact time, the aluminum concentration in water and the expenses for water treatment.

  2. 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

  3. Recombinant Factor VIIa Reduces Bleeding after Blunt Liver Injury in a Pig Model of Dilutional Coagulopathy under Severe Hypothermia.

    Directory of Open Access Journals (Sweden)

    Henri M H Spronk

    Full Text Available Recombinant factor VIIa (rFVIIa is registered for use in haemophilia with inhibitors and other rare bleeding disorders, but has also been used in various other clinical conditions to terminate life-threatening bleeding. Underlying conditions (e.g. coagulopathy and dosing may affect treatment efficacy. The objective of the present study was to evaluate the impact of increasing doses of rFVIIa on blood loss and coagulation assays in haemodiluted and hypothermic pigs undergoing blunt liver injury.A grade III blunt liver injury was induced in 28 pigs after 70% haemodilution and cooling to 32.6-33.4°C. Ten minutes after trauma, animals randomly received placebo or 90, 180 or 360 μg/kg rFVIIa. Global coagulation parameters, thromboelastometry (TEM and plasma thrombin generation (TG were determined at different time points during the observation period of 120 minutes.Total blood loss was significantly lower following 90 μg/kg rFVIIa (1206 [1138-1470] mL relative to placebo (2677 [2337-3068] mL; p<0.05, with no increased effect with higher dose levels of rFVIIa. Following trauma and haemodilution, coagulation was impaired relative to baseline in both TEM and TG analysis. At 60 and 120 minutes after trauma, TEM variables improved in the rFVIIa-treated animals compared with the placebo group. Similarly, rFVIIa improved coagulation kinetics in TG. As was observed with blood loss, no significant effect between different rFVIIa dose levels was found in TEM or TG. Macro- and microscopic post-mortem examination did not reveal any signs of thromboembolic events.Early administration of 90 μg/kg rFVIIa reduced blood loss in pigs undergoing blunt liver injury even after severe haemodilution and hypothermia, with no further effect of higher dose levels. Coagulation assays showed impaired coagulation in coagulopathic animals, with a dose-independent improvement in animals treated with rFVIIa.

  4. Performance Verification of Precil C2000-A Automatic Blood Coagulation Instrument%普利生C2000-A全自动血凝仪的性能验证

    Institute of Scientific and Technical Information of China (English)

    张伟坚; 刘光明; 梁凤琼

    2014-01-01

    目的:对全自动血凝仪普利生C2000-A进行性能验证,以确定其是否符合临床检测要求。方法参照美国临床实验室标准化委员会(NCCLS)标准,应用定值质控血浆或(和)定标血浆,选择凝血常规项目[D-二聚体(D-D)、血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶原时间测定(TT)、纤维蛋白原(FIB)]对仪器分析系统的精密度、正确度、携带污染率、线性范围、抗干扰能力(干扰物为血红蛋白、直接胆红素和三酰甘油)以及通道一致性等性能进行验证和初步评价。结果所有凝血检测项目中,批内精密度均小于3%,批间精密度均小于5%;定值质控品或者定值校准品的结果与各自靶值相比其偏差均少于8%;线性验证标本按一定比例稀释后将所得理论值与实测值进行回归分析,a值均介于0.97~1.03范围内,r均大于0.975,符合线性相关要求;携带污染率均小于3%;干扰试验的偏离值均小于3%;在4个通道上各项目的测定结果差异均无统计学意义(P>0.05),说明其通道一致性良好。结论国产血凝仪普利生C2000-A全自动血凝仪具有良好的分析性能,其准确度、精密度、线性范围、携带污染率等指标均符合质量管理要求,特别是其对溶血、黄疸以及脂浊标本具有较强的抗干扰能力,可完全满足临床检测要求。%Objective To verify the performance of the full automatic blood coagulation analy-zer precil C2000-A,and to determine whether it meets the requirements of clinical detection. Methods According to American Committee for Clinical Laboratory Standards,the precision,ac-curacy,carryover,linear range,anti-interference capability (interfering agents included hemoglo-bin,direct bilirubin and triacylglycerol)and channel consistency were verified and evaluated.Re-sults Of the all blood coagulation detection

  5. 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.

  6. Coagulation And Hemagglutination Properties Of The Crude Extract Derived From The Leaves Of Euphorbia Hirta L. Tridax Procumbens L. And Vernonia Cinerea L Less

    Directory of Open Access Journals (Sweden)

    Romeo C. Ongpoy

    2015-08-01

    Full Text Available This study aims to investigate the potential of selected wild grasses from the Philippines as coagulant and typing sera. To do this Euphorbia hirta L. Tridax procumbens L. and Vernonia cinerea L Less aqueous infusions were each subjected to blood components from healthy individuals. The plasma part of the blood was used to test for coagulation where Plasma Clotting Time PCT and Factor VIII screening test were the procedures used to test the different leaf extracts. On the other hand the Packed Red Blood Cell part of the blood was used to test for hemagglutination where microscopic and macroscopic evaluations were the procedures used to test the different leaf extracts against the blood groups from the ABO system. About this study it was found out that all the wild grasses did not give a comparable coagulation to the commercially available positive control which is Calcium Chloride while Euphorbia hirta L. gave a positive hemagglutination to Type A and Type B cells Tridax procumbens L. gave a positive hemagglutination to Type A cell and Vernonia cinerea L Less gave a positive hemagglutination to Type B cells both in macroscopic and microscopic evaluations. The results show that all the wild grasses tested may not be used as a coagulant but all of them may have a potential as a typing sera.

  7. Estado actual del mecanismo de la coagulación sanguínea Present state of the blood coagulation mechanism

    OpenAIRE

    Alina Díaz Concepción; Delfina Almagro Vázquez

    2001-01-01

    Actualmente se acepta de forma categórica que el evento iniciador principal de la coagulación sanguínea es la exposición del factor tisular (FT), lo cual da lugar a la formación del complejo factor VIIa/FT que activa a los factores IX y X en la superficie de las células que expresan el FT, y se forman las primeras cantidades de trombina. Esta trombina ejerce múltiples funciones en el mecanismo hemostático, pero es insuficiente para lograr una hemostasia eficaz, lo cual solo se logra con el en...

  8. Identification of inflammatory factor TNFα inhibitor from medicinal herbs.

    Science.gov (United States)

    Ye, Hong; Wang, Yali; Bennett Jenson, A; 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

  9. Microbes bind complement inhibitor factor H via a common site.

    Science.gov (United States)

    Meri, T; Amdahl, H; Lehtinen, M J; Hyvärinen, S; McDowell, J V; Bhattacharjee, A; Meri, S; Marconi, R; Goldman, A; Jokiranta, T S

    2013-01-01

    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." PMID:23637600

  10. Effect of hemocoagulase actutus for injection on blood coagulation function in rabbits%注射用尖吻蝮蛇凝血酶对兔凝血功能的影响

    Institute of Scientific and Technical Information of China (English)

    樊华; 张鹏; 康强; 王秀英

    2013-01-01

    OBJECTIVE To investigate the effect of hemocoagulase actutus for injection (Hem) on the blood coagulation system in rabbits. METHODS The rabbits were divided into four groups. Three groups were given 0.25, 0.5 and 1.0 U·kg-1 of Hem separately by ear intravenous injection, and one group was given hemocoagulase atrox for injection (HAI) 1.0 Klobusitzky unit (KU)·kg-1 as positive control group. Before administration and 10 min, 30 min, 2 h and 12 h after administration, the coagulation time (CT) and platelet ( PLT) were determined with Lee-White tube method and globulimeter, respectively. The prothrombin time (PT), thrombin time (TT), fibrinogen( FIB) and activated partial thromboplatin (APTT) were measured by C2000-4 high performance blood coagulation analyzer. RESULTS No index at different times in normal control group had obvious change. CT was shorted 10 min-12 h after Hem0.25, 0.5 and 1.0 U·kg-1 and HAI 1.0 KU·kg-1were given (P<0.05). PLT was increased 10-30 min after Hem 1.0 U· kg-1 ( P < 0. 05) was adminstered. APTT was declined 10 min-2 h after Hem 1.0 U·kg-1 was given and 30 min-12 h after HAI 1.0 KU·kg-1 (P<0.05) was given. PT was shorted 10 min after Hem 0.25 U·kg-1,10 min -2 h after Hem 0.5 U·kg-1,10 -30 min after Hem 1.0 U·kg-1 and 10-30 min after HAI 1.0 KU·kg-1 (P<0.05). TT was decreased 10 min-12 h after Hem 1.0 U·kg-1 and 30 min after HAI 1. 0 KU ·kg-1 (P <0. 05). FIB was increased 30 min after Hem 0.25 U·kg-1,10-30 min after Hem0.5 U·kg-1, 10 min-2 h after Hem 1.0 U·kg-1 and 10-30 min after HAl 1.0 KU · kg-1 (P < 0.05). CONCLUSION Hem 1.0 U · kg-1 remarkably promotes blood coagulation 10 min after administration, and the decrease of TT lasts for 12 h.%目的 研究注射用尖吻蝮蛇凝血酶(Hem)对兔凝血功能的影响,为临床应用提供实验依据.方法 于日本大耳白兔耳静脉分别一次性iv给予Hem 0.25,0.5和1.0 U·kg-1和阳性对照药注射用血凝酶(HAI)1.0克氏单位(KU)·kg-1,于给药前(0 min

  11. The Soluble Epoxide Hydrolase Inhibitor AR9281 Decreases Blood Pressure, Ameliorates Renal Injury and Improves Vascular Function in Hypertension

    Directory of Open Access Journals (Sweden)

    Sean Shaw

    2009-12-01

    Full Text Available Soluble epoxide hydrolase inhibitors (sEHIs are demonstrating promise as potential pharmaceutical agents for the treatment of cardiovascular disease, diabetes, inflammation, and kidney disease. The present study determined the ability of a first-inclass sEHI, AR9281, to decrease blood pressure, improve vascular function, and decrease renal inflammation and injury in angiotensin hypertension. Rats were infused with angiotensin and AR9281 was given orally during the 14-day infusion period. Systolic blood pressure averaged 180 ± 5 mmHg in vehicle treated and AR9281 treatment significantly lowered blood pressure to 142 ± 7 mmHg in angiotensin hypertension. Histological analysis demonstrated decreased injury to the juxtamedullary glomeruli. Renal expression of inflammatory genes was increased in angiotensin hypertension and two weeks of AR9281 treatment decreased this index of renal inflammation. Vascular function in angiotensin hypertension was also improved by AR9281 treatment. Decreased afferent arteriolar and mesenteric resistance endothelial dependent dilator responses were ameliorated by AR9281 treatment of angiotensin hypertensive rats. These data demonstrate that the first-in-class sEHI, AR9281, lowers blood pressure, improves vascular function and reduces renal damage in angiotensin hypertension.

  12. Epidermal Growth Factor Receptor Inhibitors: A Review of Cutaneous Adverse Events and Management

    OpenAIRE

    Chanprapaph, K.; Vachiramon, V.; Rattanakaemakorn, P.

    2014-01-01

    Epidermal growth factor inhibitors (EGFRI), the first targeted cancer therapy, are currently an essential treatment for many advance-stage epithelial cancers. These agents have the superior ability to target cancers cells and better safety profile compared to conventional chemotherapies. However, cutaneous adverse events are common due to the interference of epidermal growth factor receptor (EGFR) signaling in the skin. Cutaneous toxicities lead to poor compliance, drug cessation, and psychos...

  13. 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 ...

  14. Slaughterhouse Wastewater Treatment by Combined Chemical Coagulation and Electrocoagulation Process

    OpenAIRE

    Edris Bazrafshan; Ferdos Kord Mostafapour; Mehdi Farzadkia; Kamal Aldin Ownagh; Amir Hossein Mahvi

    2012-01-01

    Slaughterhouse wastewater contains various and high amounts of organic matter (e.g., proteins, blood, fat and lard). In order to produce an effluent suitable for stream discharge, chemical coagulation and electrocoagulation techniques have been particularly explored at the laboratory pilot scale for organic compounds removal from slaughterhouse effluent. The purpose of this work was to investigate the feasibility of treating cattle-slaughterhouse wastewater by combined chemical coagulation an...

  15. Blood plasma fractionaing and the safety against viruses; Kessho bunkaku to uirusu anzensei

    Energy Technology Data Exchange (ETDEWEB)

    Tomono, T.

    1997-05-05

    This paper describes the outline of a typical method of fractionating blood plasma for blood plasma fractional products, and introduces various kinds of operation contributing to the study of measures against viruses. The main fractional products include human blood serum albumin (Alb), human immunoglobulin (IgG) and a blood coagulation factor products. Although blood plasma can be used for the first two product, fresh freezed blood plasma is needed for the coagulation factor products. The blood plasma fractionating methods include methods utilizing the solubility difference of protein, methods, such as chromatography in which the interaction between blood plasma and protein is utilized, and methods utilizing a physical field. The virus inactivation methods include heat treatment methods, treatment methods using an organic solvent and a surfactant, and photochemical inactivation methods, by ultraviolet ray irradiation. The virus removing methods include the Cone fractionating method, methods of removing viruses by chromatography, and membrane filtration removing methods. 12 refs., 5 figs., 3 tabs.

  16. Childhood Blood Pressure Trends and Risk Factors for High Blood Pressure: The NHANES experience 1988–2008

    OpenAIRE

    Rosner, Bernard; Cook, Nancy R.; Daniels, Stephen; Falkner, Bonita

    2013-01-01

    The obesity epidemic in children makes it plausible that prevalence rates of elevated blood pressure are increasing over time. Yet, previous literature is inconsistent due to small sample sizes. Also, it is unclear whether adjusting for risk factors can explain longitudinal trends in prevalence of elevated blood pressure. Thus, we analyzed a population-based sample of 3,248 children in National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and 8,388 children in continuous N...

  17. 人凝血因子Ⅸ乳腺特异表达载体的构建及细胞转染%Construction of Human CoaguLation Factor Ⅸ Mammary Expression Vector and Transfection

    Institute of Scientific and Technical Information of China (English)

    韩雪洁; 萨日娜; 梁浩; 李雪玲; 李荣凤

    2014-01-01

    [Objective]Human coagulation factor Ⅸ (hFIX) plays a key role in blood coagulation and is important for clinical treatment of hemophilia. The objective of this study is to construct human coagulation factor Ⅸ (hFIX) mammary expression vector and test the expression of hFIX in porcine mammary epithelial, and obtain hFIX-transgenic porcine mammary epithelial and female porcine fetal fibroblast cells to prepare to produce hFIX mammary specific expression transgenic pigs .[Method]Total RNA was extracted from human fetal liver tissues and human coagulation factor Ⅸ (hFIX) cDNA was amplified by RT-PCR followed the instructions of RNAiso Reagent and Prime Script RT-PCR Kit from TAKARA. PCR was performed to amplify bovine growth hormone (BGH) polyA fragment. Both hFIX cDNA and BGH polyA fragments were cloned to pbCSN2-RC plasmid, located after the bovine beta-Casein (CSN2) promoter, to achieve mammary specific expression vector pbCSN2-hFIX-pA-RC with neomycin-resistance and red fluorescence genes. Porcine mammary epithelial cells were obtained by culturing 1mm3 mammary tissue cubes from the breast tissue of lactation pigs that slaughtered in the local slaughterhouse and purifying with time-controlled trypsinization. The chromosome analysis was performed on the derived cells, and the cells with normal number of chromosomes were transfected with pbCSN2-hFIX-pA-RC by lipofection technology. The transfected porcine mammary epithelial cells were screened by neomycin-resistance and red fluorescent expression. The expression of hFIX was further confirmed by real-time PCR. To only transfect the female fibroblasts, the SRY PCR was performed on the porcine fibroblasts cultured in the lab to determine the sex of the cells. Finally, the confirmed vector was transferred to porcine fetal fibroblast cells by lipofection technology. [Result] The results of PCR and restricted endonucleases digestion analysis showed that the hFIX cDNA and BGH PolyA were cloned into pbCSN2-RC, and the

  18. Blood component therapy: Which, when and how much

    Directory of Open Access Journals (Sweden)

    Rajesh Chand Arya

    2011-01-01

    Full Text Available Blood transfusion refers to the perioperative administration of blood and blood components. Adherence to proper indications for blood component therapy is essential because of its potential adverse effects and costs of transfusion. Over the years, the significance of blood components in treating certain diseases or conditions has been recognized. In this article, the most commonly used blood components along with the new developments in component therapy have been discussed. Recommendations by different academic and clinical trials and studies have been presented for quick reference. The individual coagulation factors are discussed in brief.

  19. Disseminated Mycobacterium chelonae Infection in a Patient Receiving an Epidermal Growth Factor Receptor Inhibitor for Advanced Head and Neck Cancer

    OpenAIRE

    Bark, Charles M.; Traboulsi, Rana S.; Honda, Kord; Starnes, Autumn M.; Jacobs, Michael R.; Rodriguez, Benigno

    2012-01-01

    We report a case of disseminated cutaneous Mycobacterium chelonae infection in a patient with head and neck cancer on salvage chemotherapy, including the epidermal growth factor receptor inhibitor cetuximab. Mycobacterium chelonae should be considered in the differential diagnosis of cutaneous infections in cancer patients receiving epidermal growth factor receptor inhibitors.

  20. Recent Advances in Developing Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylases and Their Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    So Yeon Kim

    2015-11-01

    Full Text Available Hypoxia-inducible factor (HIF prolyl hydroxylases (PHDs are members of the 2-oxoglutarate dependent non-heme iron dioxygenases. Due to their physiological roles in regulation of HIF-1α stability, many efforts have been focused on searching for selective PHD inhibitors to control HIF-1α levels for therapeutic applications. In this review, we first describe the structure of PHD2 as a molecular basis for structure-based drug design (SBDD and various experimental methods developed for measuring PHD activity. We further discuss the current status of the development of PHD inhibitors enabled by combining SBDD approaches with high-throughput screening. Finally, we highlight the clinical implications of small molecule PHD inhibitors.

  1. THE PROBLEMS OF THE SAFETY OF THERAPY WITH TUMOR NECROSIS FACTORINHIBITORS

    Directory of Open Access Journals (Sweden)

    Dmitry Evgenyevich Karateyev

    2009-09-01

    Full Text Available Due to the fact that tumor necrosis factor-а (TNF-а inhibitors are in wide use, the problem of the safety of therapy with drugs of this group is pressing. The review discusses the data of randomized and observational clinical trials of three drugs of this group (adalimumab, infliximab, and etanercept whether they can cause serious adverse reactions (SAR. The analysis leads to the conclusion that 10 years' experience in using TNF-а inhibitors generally suggests their satisfactory safety profile. Anti-TNF-а therapy is unassociated with the increased risk of fatal outcomes, at the same time one should be alert to tuberculosis, serious bacterial infections, and lymphoma although the frequency of SAR is generally low; the risk for the development of SAR becomes higher as the dose of TNF-а inhibitors is increased and it does not with longer survival. The currently available preventive methods and physicians' alertness to SAR help prevent their development.

  2. Modulation of C1-Inhibitor and Plasma Kallikrein Activities by Type IV Collagen

    OpenAIRE

    Sriram Ravindran; Marc Schapira; Patston, Philip A.

    2012-01-01

    The contact system of coagulation can be activated when in contact with biomaterials. As collagen is being tested in novel biomaterials in this study, we have investigated how type IV collagen affects plasma kallikrein and C1-inhibitor. Firstly, we showed C1-inhibitor binds to type IV collagen with a Kd of 0.86 μM. The effects of type IV collagen on plasma kallikrein, factor XIIa, and β-factor XIIa activity and on C1-inhibitor function were determined. Factor XIIa rapidly lost activity in the...

  3. Fatores associados à incoagulabilidade sangüínea no envenenamento por serpentes do gênero Bothrops Risk factors associated with coagulation abnormalities in Bothrops envenoming

    Directory of Open Access Journals (Sweden)

    Ricardo Borges de Oliveira

    2003-12-01

    Full Text Available Com o objetivo de conhecer fatores associados à incoagulabilidade sangüínea no envenenamento botrópico, foram obtidas informações de 2.991 prontuários médicos de pacientes atendidos no Instituto Butantan de 1981 a 1990. Associaram-se positivamente à incoagulabilidade sangüínea (p0,05: horário do acidente; presença de presa recém-deglutida no tubo digestivo da serpente; sexo e idade do paciente; ocorrência de bolha, necrose, abscesso e incisão local, amputação, insuficiência renal e óbito. Pode-se concluir que, embora a incoagulabilidade sangüínea apresente associação com manifestações precoces do envenenamento, não tem boa associação com a evolução clínica do paciente.This study aimed at assessing, in the envenoming by Bothrops, factors that are associated with blood incoagulability. Information was obtained from the charts of 2,991 patients admitted to Instituto Butantan, from 1981 to 1990. Factors positively associated with blood incoagulability (p0.05 were: time of the bite; presence of recently swallowed prey in the snake gut; gender and age of the patient; blister, necrosis, and abscess at the bite site; occurrence of amputation, renal failure and death; presence of an incision at the bite site. We conclude that although blood incoagulability is associated with early manifestations of Bothrops envenoming, it is not associated with the clinical outcome.

  4. Pharmacophore Selection and Redesign of Non-nucleotide Inhibitors of Anthrax Edema Factor

    Directory of Open Access Journals (Sweden)

    Maria Estrella Jimenez

    2012-11-01

    Full Text Available Antibiotic treatment may fail to protect individuals, if not started early enough, after infection with Bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. Stable and easily stored inhibitors of the edema factor toxin (EF, an adenylyl cyclase, could save lives in the event of an outbreak, due to natural causes or a bioweapon attack. The toxin’s basic activity is to convert ATP to cAMP, and it is thus in principle a simple phosphatase, which means that many mammalian enzymes, including intracellular adenylcyclases, may have a similar activity. While nucleotide based inhibitors, similar to its natural substrate, ATP, were identified early, these compounds had low activity and specificity for EF. We used a combined structural and computational approach to choose small organic molecules in large, web-based compound libraries that would, based on docking scores, bind to residues within the substrate binding pocket of EF. A family of fluorenone-based inhibitors was identified that inhibited the release of cAMP from cells treated with EF. The lead inhibitor was also shown to inhibit the diarrhea caused by enterotoxigenic E. coli (ETEC in a murine model, perhaps by serving as a quorum sensor. These inhibitors are now being tested for their ability to inhibit Anthrax infection in animal models and may have use against other pathogens that produce toxins similar to EF, such as Bordetella pertussis or Vibrio cholera.

  5. Which Factors Influence Radiographic Progression During Treatment with Tumor Necrosis Factor Inhibitors in Clinical Practice?

    DEFF Research Database (Denmark)

    Ornbjerg, Lykke Midtbøll; Ostergaard, Mikkel; Bøyesen, Pernille; Krogh, Niels Steen; Thormann, Anja; Tarp, Ulrik; Poulsen, Uta Engling; Espesen, Jakob; Schlemmer, Annette; Graudal, Niels; Kollerup, Gina; Jensen, Dorte Vendelbo; Madsen, Ole Rintek; Glintborg, Bente; Christensen, Torben; Lindegaard, Hanne; Bøhme, Wolfgang; Hansen, Annette; Andersen, Anne Rødgaard; Hetland, Merete Lund

    2014-01-01

    -59), DAS28-CRP 5.0 (1.4-7.8), TSS median 15 [3-45 interquartile range (IQR)] and mean 31 (SD 40). Patients started treatment with infliximab (59%), etanercept (18%), or adalimumab (23%). At followup (median 526 days, IQR 392-735), 61% were treated with the initial anti-TNF, 29% had switched TNF inhibitor...

  6. Risk Factors for Hepatitis C Virus Infection among Blood Donors in Georgia

    International Nuclear Information System (INIS)

    Background: Growing awareness about the importance of blood safety for controlling the transmission of hepatitis C virus (HCV) has helped to decrease the spread of this virus in many settings. This study was conducted in order to evaluate potential risk factors for HCV infection among blood donors in Georgia. Methods: The study population consisted of 553 blood donors in three major Georgian cities; Tbilisi, the capital city and Batumi and Poti, naval port cities. Risk factors were examined using a behavior questionnaire. All blood samples were initially tested using 3rd generation anti-HCV enzyme-linked immunosorbent assays and confirmed using recombinant immunoblot assays and nucleic acid testing. Results: Forty-three blood donors, 7.8%, were confirmed HCV positive. Significant risk factors included: drug injection ever (OR: 42; 95% CI: 3.2-550.7); history of hepatitis (OR: 25.9; 95% CI: 4.6-145.5); history of a previous surgical procedure (OR: 148.4; 95% CI: 26.9-817.4); blood transfusion (OR: 25.9; 95% CI: 3.2-210.9). Conclusions: This study found a very high prevalence of HCV among blood donors in Georgia. The main risk factor for HCV infection in this population of blood donors was previous contact with contaminated blood or blood products. Reliable screening of donors and their blood is critical for controlling the further spread of HCV in Georgia

  7. Is there an effect of folic acid supplementation on the coagulation factors and C-reactive protein concentrations in subjects with atherosclerosis risk factors

    Directory of Open Access Journals (Sweden)

    Artur Mierzecki

    2012-10-01

    Full Text Available Introduction:Folic acid (FA may delay the formation of atherosclerotic lesions. Increased plasma levels of von Willebrand factor (VWF are observed in cardiovascular disease, which leads to higher risk of thrombosis. Fibrinogen (Fb is a well-documented risk factor of cardiovascular disease. The aim of this study was to analyze the effect of FA supplementation on the Fb, VWF and C-reactive protein (CRP plasma concentrations in subjects with atherosclerosis risk factors.Material/Methods:The study enrolled 124 Caucasian individuals (60 M, 64 F with atherosclerosis risk factors – family history of premature ischaemic stroke, arterial hypertension, dyslipidaemia, overweight and obesity, cigarette smoking and low physical activity. The participants were asked to take FA in the low dose of 0.4 mg/24 h for three months.Results:After FA supplementation a significant reduction of the VWF concentrations in females (76.6 vs 72.3�20p=0.028 and in males (75.5 vs 66.9�20p=0.001 was observed. Among women and men with dyslipidaemia concentrations of VWF decreased after FA supplementation (76.8�0vs 69.6�20p=0.003 and 76.7�0vs 67.8�20p=0.001 respectively. Among females and males with BMI ≥25 kg/m2 concentrations of VWF decreased only in men (77.6�0vs 66.5�20p=0.001. In female and male smokers supplementation of FA decreased VWF concentrations (82.5�0vs 74.4�20p=0.012 and 76.6�0vs 69.5�20p=0.036 respectively.Discussion:The results of our study suggest that there is an effect of FA supplementation on VWF concentrations in subjects with atherosclerosis risk factors

  8. [Blood viscosity and blood factors in non-embolic cerebral infarction].

    Science.gov (United States)

    Fong, C S; Chia, L G

    1990-11-01

    We compared blood viscosity at a high and a low shear rate, hematocrit, as well as levels of fibrinogen, cholesterol, triglyceride and high density lipoprotein-cholesterol between 42 patients with nonembolic cerebral infarction and 39 normal subjects. Blood viscosity, levels of fibrinogen, cholesterol and triglyceride were significantly higher, and high density lipoprotein-cholesterol levels were significantly lower, in patients than in normal persons. Blood viscosity had a positive correlation with hematocrit and fibrinogen, and a negative correlation with high density lipoprotein-cholesterol, but no correlation with cholesterol and triglyceride. PMID:1982124

  9. Vascular endothelial growth factor inhibitors: investigational therapies for the treatment of psoriasis

    Directory of Open Access Journals (Sweden)

    Weidemann AK

    2013-09-01

    Full Text Available Anja K Weidemann,1 Ania A Crawshaw,2 Emily Byrne,3 Helen S Young1 1The Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester, UK; 2Royal Sussex County Hospital, Brighton, UK; 3University Hospital of South Manchester, Manchester, UK Abstract: Psoriasis is a common inflammatory autoimmune condition in which environmental factors and genetic predisposition contribute to the development of disease in susceptible individuals. Angiogenesis is known to be a key pathogenic feature of psoriasis. Local and systemic elevation of vascular endothelial growth factor (VEGF-A has been demonstrated in the skin and plasma of patients with psoriasis and is known to correlate with improvement following some traditional psoriasis treatments. A number of VEGF inhibitors are licensed for the treatment of malignancies and eye disease and isolated case reports suggest that some individuals with psoriasis may improve when exposed to these agents. The small number of cases and lack of unified reporting measures makes it difficult to draw generalizations and underline the heterogeneity of psoriasis as a disease entity. Though not yet licensed for the treatment of psoriasis in humans, experimental data supports the potential of VEGF inhibitors to influence relevant aspects of human cell biology (such as endothelial cell differentiation and to improve animal models of skin disease. Given the multi-factorial nature of psoriasis it is unlikely that VEGF inhibitors will be effective in all patients, however they have the potential to be a valuable addition to the therapeutic arsenal in selected cases. Current VEGF inhibitors in clinical use are associated with a number of potentially serious side effects including hypertension, left ventricular dysfunction, and gastrointestinal perforation. Such risks require careful consideration in psoriasis populations particularly in light of growing concerns linking psoriasis to increased

  10. 42 CFR 410.63 - Hepatitis B vaccine and blood clotting factors: Conditions.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Hepatitis B vaccine and blood clotting factors... Other Health Services § 410.63 Hepatitis B vaccine and blood clotting factors: Conditions... under § 410.10, subject to the specified conditions: (a) Hepatitis B vaccine: Conditions....

  11. EFFECTS OF ACUPUNCTURE ON THE HIGH HEMAGGLUTINATION STATE, BLOOD-SUGAR-RAISING HORMONE AND IMMUNOCYTE FACTOR LEVELS IN TYPE-Ⅱ DIABETES PATIENTS

    Institute of Scientific and Technical Information of China (English)

    Chen Jianfei; Ma Yalin; Cai Shaohua; Liang Haorong; Shen Jing

    2001-01-01

    Objective: To investigate the effect of acupuncture on high hemagglutination state, blood-sugar-raising hormone and immunocyte facto r levels In type-Ⅱ diabetes patients. Methods: A total of 120 inpatients and outpatients were randomly divided into acupuncture plus medication group (n = 52) and medication group (n= 50). In addition, 18 type-Ⅱ diabetes patients formed acupuncture group for comparing their therapeutic effects. Main acupoints used were Pishu (BL 20), Geshu (BL 17), Yishu, Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), etc.. combined with other acupoints according to different sydroms. These acupoints were stimulated by manipulaing the filiform needles with uniform reinforcing and reducing method for 15 min and then stimulated electrically for 15 min with an electroacupuncture therapeutic apparatus. Western medicines used were Glipizide, Dimethyldiguanide Hydrochloride,etc.. The treatment was given once daily, with 10 sessions being a therapeutic course, 2~3 courses altogether. Indexes of external thrombosis length (ETL), platelet agglutination rate (PAgR), fibrinogen (FG), activated partial thromboplastin time (APTT), fasting blood glucose (FBG), prothrombin time (PT), adrenocoticortropic hormone (ACTH), cortisol (CS), growth hormone (GH), glucagon (GL), tumor necrosis factor alpha (TNF-α), interleukin-6(IL-6), insulin (INS) and C-peptide (C-P) were determined using radioimmunoassay. Results: After 2~ 3 courses of treatment, both acupuncture group and medication plus acupuncture group could significantly improve high hemagglutination state, lower blood-sugar-raising hormone level, regulate immunocyte factor level and raise the sensitivity of insulin, which were apparently superior to those of medication group (P<0.05~0.01 ). Conclusion: Acupuncture therapy can effectively regulate plasma blood-sugar-raising hormone, immunocyte factor levels, increase the sensitivity of insulin to target cells, resist blood coagulation and improve

  12. Estrogens, selective estrogen receptor modulators, and a selective estrogen receptor down-regulator inhibit endothelial production of tissue factor pathway inhibitor 1

    Directory of Open Access Journals (Sweden)

    Ree Anne

    2006-10-01

    Full Text Available Abstract Background Hormone therapy, oral contraceptives, and tamoxifen increase the risk of thrombotic disease. These compounds also reduce plasma content of tissue factor pathway inhibitor-1 (TFPI, which is the physiological inhibitor of the tissue factor pathway of coagulation. The current aim was to study if estrogens and estrogen receptor (ER modulators may inhibit TFPI production in cultured endothelial cells and, if so, identify possible mechanisms involved. Methods Human endothelial cell cultures were treated with 17β-estradiol (E2, 17α-ethinylestradiol (EE2, tamoxifen, raloxifene, or fulvestrant. Protein levels of TFPI in cell media and cell lysates were measured by an enzyme-linked immunosorbent assay, and TFPI mRNA levels were assessed by quantitative PCR. Expression of ERα was analysed by immunostaining. Results All compounds (each in a concentration of 10 nM reduced TFPI in cell medium, by 34% (E2, 21% (EE2, 16% (tamoxifen, and 28% (raloxifene, respectively, with identical inhibitory effects on cellular TFPI levels. Expression of TFPI mRNA was principally unchanged. Treatment with fulvestrant, which was also associated with down-regulation of secreted TFPI (9% with 10 nM and 26% with 1000 nM, abolished the TFPI-inhibiting effect of raloxifene, but not of the other compounds. Notably, the combination of 1000 nM fulvestrant and 10 nM raloxifene increased TFPI secretion, and, conversely, 10 nM of either tamoxifen or raloxifene seemed to partly (tamoxifen or fully (raloxifene counteract the inhibitory effect of 1000 nM fulvestrant. The cells did not express the regular nuclear 66 kDa ERα, but instead a 45 kDa ERα, which was not regulated by estrogens or ER modulators. Conclusion E2, EE2, tamoxifen, raloxifene, and fulvestrant inhibited endothelial production of TFPI by a mechanism apparently independent of TFPI transcription.

  13. How real is the long-lasting effect of tumor necrosis factor α inhibitors? Focus on immunogenicity

    Directory of Open Access Journals (Sweden)

    D.E. Karateev

    2014-05-01

    Full Text Available Tumor necrosis factor (TNF α inhibitors are the most commonly used agents to treat rheumatoid arthritis (RA and other inflammatory arthropathies. Five drugs belonging to the family of TNFα inhibitors have been certified in Russia for treating RA: infliximab (INF, adali- mumab (ADA, golimumab, certolizumab pegol, and etanercept (ETN. These drugs have different compositions. ETN does not belong to the family of monoclonal antibodies (mAbs and has a different mechanism of action. It is a dimeric molecule of synthetic fusion protein contain- ing TNF receptor and bound to the Fc-fragment of human Ig1. ETN can inhibit both TNFα and lymphotoxin α. ETN contains only the pro- tein identical to human protein. All TNFα inhibitors exhibit a virtually identical anti-inflammatory activity. The data from the registries show that the risk of discontinuation of therapy with TNFα during the first 2–3 years is appreciably high; there is a trend toward increased frequency of therapy discontinuation because of loss of effectiveness. It was found that the risk of therapy discontinuation because of insufficient effectiveness and adverse events (AEs is minimal for ETN and maximal for INF. The structure of biological drugs (which also affects their immunogenicity has the key neg- ative effect on maintaining the response to therapy and frequency of AEs. However, since ETN is a fusion molecule and contains less poten- tially immunogenic epitopes compared to mAbs, the frequency of detecting anti-drug antibodies (ADAbs is appreciably lower. The fact that ETN has a lower immunogenicity can be used to explain the significantly lower probability of discontinuing therapy using this drug as compared to INF and ADA. The risk that the need to increase the dose because of gradual loss of effectiveness of therapy with ADA and INF, was 4.9- and 28-fold higher, respectively, as compared to ETN. Therapeutic algorithms make it possible to control therapy with TGFα inhibitors

  14. How real is the long-lasting effect of tumor necrosis factor α inhibitors? Focus on immunogenicity

    Directory of Open Access Journals (Sweden)

    D.E. Karateev

    2014-01-01

    Full Text Available Tumor necrosis factor (TNF α inhibitors are the most commonly used agents to treat rheumatoid arthritis (RA and other inflammatory arthropathies. Five drugs belonging to the family of TNFα inhibitors have been certified in Russia for treating RA: infliximab (INF, adali- mumab (ADA, golimumab, certolizumab pegol, and etanercept (ETN. These drugs have different compositions. ETN does not belong to the family of monoclonal antibodies (mAbs and has a different mechanism of action. It is a dimeric molecule of synthetic fusion protein contain- ing TNF receptor and bound to the Fc-fragment of human Ig1. ETN can inhibit both TNFα and lymphotoxin α. ETN contains only the pro- tein identical to human protein. All TNFα inhibitors exhibit a virtually identical anti-inflammatory activity. The data from the registries show that the risk of discontinuation of therapy with TNFα during the first 2–3 years is appreciably high; there is a trend toward increased frequency of therapy discontinuation because of loss of effectiveness. It was found that the risk of therapy discontinuation because of insufficient effectiveness and adverse events (AEs is minimal for ETN and maximal for INF. The structure of biological drugs (which also affects their immunogenicity has the key neg- ative effect on maintaining the response to therapy and frequency of AEs. However, since ETN is a fusion molecule and contains less poten- tially immunogenic epitopes compared to mAbs, the frequency of detecting anti-drug antibodies (ADAbs is appreciably lower. The fact that ETN has a lower immunogenicity can be used to explain the significantly lower probability of discontinuing therapy using this drug as compared to INF and ADA. The risk that the need to increase the dose because of gradual loss of effectiveness of therapy with ADA and INF, was 4.9- and 28-fold higher, respectively, as compared to ETN. Therapeutic algorithms make it possible to control therapy with TGFα inhibitors

  15. MEK inhibitors, novel anti-adhesive molecules, reduce sickle red blood cell adhesion in vitro and in vivo, and vasoocclusion in vivo.

    Directory of Open Access Journals (Sweden)

    Rahima Zennadi

    Full Text Available In sickle cell disease, sickle erythrocyte (SSRBC interacts with endothelial cells, leukocytes, and platelets, and activates coagulation and inflammation, promoting vessel obstruction, which leads to serious life-threatening complications, including acute painful crises and irreversible damage to multiple organs. The mitogen-activated protein kinase, ERK1/2, is abnormally activated in SSRBCs. However, the therapeutic potential of SSRBC ERK1/2 inactivation has never been investigated. I tested four different inhibitors of MEK1/2 (MEK, the kinase that activates ERK1/2, in a model of human SSRBC adhesion to TNFα-activated endothelial cells (ECs. SSRBC MEK inhibition abrogated adhesion to non-activated and TNFα-activated ECs to levels below baseline SSRBC adhesion to non-activated ECs in vitro. SSRBC MEK inhibition also prevented SSRBCs from activating naïve neutrophils to adhere to endothelium. To determine the effect of MEK inhibitors on SSRBC adherence in vivo, sham-treated or MEK inhibitor-treated SSRBCs were infused to nude mice previously treated with TNFα. Sham-treated SSRBCs displayed marked adhesion and occlusion of enflamed vessels, both small and large. However, SSRBC treatment with MEK inhibitors ex vivo showed poor SSRBC adhesion to enflamed vessels with no visible vasoocclusion in vivo. In addition, MEK inhibitor treatment of SSRBCs reduced SSRBC organ trapping and increased the number of SSRBCs circulating in bloodstream. Thus, these data suggest that SSRBC ERK1/2 plays potentially a critical role in sickle pathogenesis, and that MEK inhibitors may represent a valuable intervention for acute sickle cell crises.

  16. Recombinant Factor VIIa (Eptacog Alfa): A Pharmacoeconomic Review of its Use in Haemophilia in Patients with Inhibitors to Clotting Factors VIII or IX

    OpenAIRE

    Katherine A. Lyseng-Williamson; Plosker, Greg L.

    2007-01-01

    Recombinant factor VIIa (NovoSeven(R); also known as recombinant activated factor VII or eptacog alfa) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In noncomparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of succe...

  17. Coagulation with limited aggregations

    CERN Document Server

    Bertoin, Jean

    2012-01-01

    Smoluchowski's coagulation equations can be used as elementary mathematical models for the formation of polymers. We review here some recent contributions on a variation of this model in which the number of aggregations for each atom is a priori limited. Macroscopic results in the deterministic setting can be explained at the microscopic level by considering a version of stochastic coalescence with limited aggregations, which can be related to the so-called random configuration model of random graph theory.

  18. Argon plasma coagulation

    Directory of Open Access Journals (Sweden)

    Zenker, Matthias

    2008-03-01

    Full Text Available Argon Plasma Coagulation (APC is an application of gas discharges in argon in electrosurgery, which is increasingly used especially in endoscopy. The major application fields are haemostasis, tissue devitalization and tissue reduction.This review describes the physics and technology of electrosurgery and APC. Some characteristics of the argon discharge are shown and discussed, and thermal effects in biological tissue are described. Subsequently, examples of medical applications are given.

  19. Coagulation and Mental Disorders

    OpenAIRE

    Silvia Hoirisch-Clapauch; Antonio Egidio Nardi; Jean-Christophe Gris; Benjamin Brenner

    2014-01-01

    The neurovascular unit is a key player in brain development, homeostasis, and pathology. Mental stress affects coagulation, while severe mental illnesses, such as recurrent depression and schizophrenia, are associated with an increased thrombotic risk and cardiovascular morbidity. Evidence indicates that the hemostatic system is involved to some extent in the pathogenesis, morbidity, and prognosis of a wide variety of psychiatric disorders. The current review focuses on emerging data linking ...

  20. Desenvolvimento de inibidores do fator VIII na hemofilia A Development of factor VIII inhibitors in hemophilia A

    Directory of Open Access Journals (Sweden)

    Daniel G. Chaves

    2009-01-01

    Full Text Available A hemofilia A é uma coagulopatia genética com herança recessiva ligada ao cromossomo X que afeta 1-2 a cada 10 mil indivíduos do sexo masculino nascidos vivos. Estes indivíduos têm baixas concentrações ou ausência do fator VIII (FVIII da coagulação no plasma e apresentam quadros hemorrágicos leves, moderados e graves, dependendo da atividade de FVIII circulante. Estes pacientes necessitam de constante reposição proteica e aproximadamente 30% deles desenvolvem aloanticorpos contra a proteína exógena. A síntese dos anticorpos anti-FVIII é iniciada quando o FVIII exógeno é endocitado por células apresentadoras de antígeno, degradado e apresentado às células T CD4+ na forma de peptídeos ligados a moléculas do complexo maior de histocompatibilidade (MHC de classe II. Alguns fatores de risco (paciente/tratamento podem ser relacionados ao desenvolvimento desta resposta imune. Neste contexto, as mutações no gene do FVIII e polimorfismos em genes envolvidos na resposta imune são candidatos moleculares como determinantes imunogenéticos na predisposição para o desenvolvimento de inibidores. Por não ser completamente entendido e controlado, o desenvolvimento desta resposta imune contra o FVIII constitui o maior problema decorrente do tratamento de indivíduos portadores de hemofilia A e faz-se necessária busca de opções que visem minimizar suas ações deletérias. Algumas alternativas de tratamento têm se mostrado eficazes no tratamento (anti-CD20, plasmaférese, concentrado de complexo protrombínico (PCCs, concentrado de complexo protrombínico ativado (APCCs, fator VII humano ativado, mas a retirada ou neutralização específica dos inibidores de FVIII ainda não foram alcançadas.Hemophilia A, which affects 1-2:10,000 live-born male neonates, is a genetic coagulopathy with recessive inheritance linked to the X chromosome. These individuals have low concentrations or no coagulation factor VIII (FVIII in the plasma