Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite more than 2 decades of research, the explanation of the long-known hemostatic failure consequent to the use of some natural and synthetic macromolecular agents as plasma substitutes remains obscure. Conventional clotting parameters are not significantly affected in vivo or in vitro. Dextran, hydroxyethyl starch, and many other colloid macromolecules precipitate Factors I and VIII, fibrin monomer, and perhaps v. W. (von Willebrand) factor(s) from plasma, rendering at least the first three insoluble, in relation to the molecule size and concentration of the colloid, and for dextran, its intrinsic viscosity. The precipitate, rich in Factors VIII and I, redissolves on warming, and reprecipitates on cooling, behaving as a cryo-Factor I. In composition it closely resembles the cryoprecipitate obtained by slow-thawing of plasma. Both clot faster with thrombin than the parent plasma. The amount precipitated from plasma by dextran or hydroxyethyl starch varies very widely from individual to individual. Cryo- of dextran-precipitable material can be obtained by interacting purified Factor I with a miniscule amount of thrombin. Dextran, hydroxyethyl starch, polyvinyl pyrrolidone, some forms of gelatin, and several polyamino acids accelerate thrombin clotting of normal plasma, several dysfibrinogenemic plasmas, or Factor I. Albumin, hemoglobin, some modified gelatins do not. Poor platelet thromboplastic function appears some hours after dextran infusion, associated with morphologic capillary abnormalities that strikingly resemble those in v. W. disease. We postulate that the hemostatic defect associated with the use of plasma substitutes is a form of induced v. W. disease or disseminated intravascular clotting, ensuing from precipitation and removal of v. W. factor(s), Factors VIII and I, microcirculatory abnormality, and platelet malfunction. The latter two supervene some time after administration of dextran. It reported antithrombotic activity is perhaps referable to the same action.
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PMID:Coagulation, hemostasis, and plasma expanders:a quarter century enigma. 4 13

An 'artificial' plasma for one-stage factor-VIII assays is made by incubating human plasma with EDTA, to destroy factor VIII, and afterwards removing the anticoagulant by dialysis. Bovine factor V is then added to a given level. In the assay, contact activation is controlled by adding contact product. It was confirmed that factor-VIII activity was destroyed and that the EDTA was freely dialysable. The fibrinogen in the treated plasma clotted normally with thrombin. Likely variation in the factor-V activity was found not to be critical. The concentration of fibrinogen and other factors was adequate. Variation between batches was small. The artificial plasma yielded assay results closely comparable to haemophilic plasma in samples with factor-VIII activities in the range 0.01--20.0 iu/ml; the mean results in the artificial system were estimated to be 0.997 x those in haemophilic plasma, with a 95% confidence interval of 0.901--1.103. Biological variability in individual assays was smaller in the artificial system than when haemophilic plasma was used. Instability at the bench was more often detected in the artificial system than in haemophilic plasma assays, but the effect was eliminated from the results by obtaining duplicated readings in a balanced order.
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PMID:An artificial 'haemophilic' plasma for one-stage factor-VIII assay. 10 60

The adequacy of anticoagulation during 2 hours of cardiopulmonary bypass at 30 degrees C in 9 rhesus monkeys was determined by measuring the whole-blood activated clotting time (ACT) and by noting the appearance of thrombin-altered fibrin (fibrin monomer) and the relative consumption of clotting factors. Factor V and VIII, the heparin cofactor, antithrombin III, prothrombin time, partial thromboplastin time, ACT, platelets, hematocrit, fibrinogen, and fibrin monomer were determined prior to heparinization and after protamine. In 6 of 9 experiments, fibrin monomer became positive in the plasma during cardiopulmonary bypass (CPB), indicating that active coagulation was occurring. In 5 of the 6 animals, initial ACT was less than 400 seconds, and fibrin monomer appeared within the first 30 minutes of bypass. In 1 animal with an initial ACT of 439 seconds, fibrin monomer appeared after 60 minutes of bypass, at which time the ACT was less than 400 seconds. An abnormal level of fibrin monomer was not detected in 5 pediatric patients with an ACT greater than 450 seconds during CPB. Our experimental study and clinical data suggest that the lower limit, as measured by the ACT, for anticoagulant effect to provide coagulation-free CPB is at least 400 seconds.
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PMID:Adequate anticoagulation during cardiopulmonary bypass determined by activated clotting time and the appearance of fibrin monomer. 11 Feb 73

The relationship between factor VIII (AHF) procoagulant activity and factor VIII-related antigen were examined in patients with disseminated intravascular coagulation (DIC), pulmonary embolism (PE), and coronary artery disease with or without myocardial infarction (MI). It was found that 13 of 13 patients with DIC, 17 of 17 patients with PE, and 10 of 12 patients with MI possessed a significantly elevated factor VIII-related antigen to factor VIII activity ratio (VIII-ratio). The VIII-ratio returned to normal in each of 2 patients with DIC and 1 paitent with PE after treatment with heparin, heparin and alpha-amino-caproic acid, and heparin and coumadin respectively. In contrast, the VIII-ratio was slightly elevated only in 1 of 15 patients with coronary artery insufficiency without MI. In in vitro studies, after treatment of plasma with thrombin or plasmin, factor VIII activity was lost, whereas the amount of factor VIII-related antigen remained the same or was even increased when measured by agarose quantitative immunoelectrophoresis. These observations have led us to conclude that an elevated VIII-ratio is a very sensitive indicator of intravascular coagulation.
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PMID:In vivo and in vitro effects of thrombin and plasmin on human factor VIII (AHF). 13 71

Cyanate reacts with unchanged amino groups of various proteins in a specific irreversible carbamylation reaction. The effect of this molecule on the clotting process and the effects of carbamylation on the clotting proteins and platelet functions were investigated in vitro. An immediate effect on the clotting proteins, not related to pH, was seen in the screening tests prothrombin time, partial thromboplastin time and thrombin time at the highest concentration (100 mM), to a lesser degree at the lower concentration (10 mM). These changes reflected decreases of 19 and 36% respectively in Factor V and X activity, an inhibition of 63-75% of Factors VII, IX, X and XI activity, and 80% inhibition of thrombin activity. The inhibitory changes of carbamylation increased with time. No changes were seen in the activity of Factors I and VIII. Platelet function studies revealed no inhibition of Factor III release; aggregation was abnormal only at high concentrations with epinephrine and collagen induction and partially reversible by resuspension in normal plasma.
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PMID:The effect of cyanate on the clotting proteins and platelet function. 23 14

The aggregation of platelets by the antibiotic, ristocetin, requires a plasma cofactor (VIII:vWF) and one or more specific binding sites on the platelet membrane. The interaction between VII:vWF and the platelet was examined using VIII:vWF labelled with 125I. In the presence of ristocetin (1.5 mg/ml), from 70 to 90% of the 125I-VIII:vWF became platelet-bound. By contrast, only 21% was bound with thrombin (2.5 microgram/ml), and 2.2% with buffer alone. Fractionation of the platelets revealed that peak radioactivity was present in the membrane fraction. Treatment of ristocetin-reacted platelets with either chymotrypsin, 100 microgram/ml, or trypsin, 75 microgram/ml, resulted in the partial release of the membrane-bound radioactivity. It is concluded that VIII:vWF binds to the platelet membrane in the presence of ristocetin.
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PMID:Platelet-binding of the von Willebrand factor. 30 91

A prospective study of hemostatic abnormalities in 108 cancer patients was undertken at an oncology clinic in a university teaching hospital. Tests included Quick prothrombin time, activated partial thromboplastin time, thrombin time, platelet count, modified Ivy bleeding time, fibrinogen, fibrin degradation products (FDP), euglobulin lysis time, protamine sulfate test, and factor V, VII, VIII and X assays. Ninety-eight per cent of the patients had one or more abnormal coagulation tests. The commonest abnormalities were elevated fibrin degradation products and prolonged thrombin time. Thrombocytosis occurred in 57% of patients, hyperfibrinogenemia in 46%, thrombocytopenia in 11%, and non had hypofibrinogenmia. It is suggested that platelet count, fibrinogen concentration, and serum FDP assay are the most useful tests in assessing the hemostatic abnormalities in cancer patients, although thrombin time, factor V assay, and bleeding time may also be helpful. The peripheral blood smears of 53 patients were reviewed, and only one showed microangiopathic hemolytic anemia. The data illustrate that subclinical coagulopathy is relatively frequent in patients with malignancy.
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PMID:Hemostatic abnormalities in malignancy, a prospective study of one hundred eight patients. Part I. Coagulation studies. 42 Jan 61

Human factor VIII has been dissociated into fragment VIII-C and fragment VIII-AG in the presence of calcium chloride (0.25 M). After removing the calcium, recombination of the molecule is obtained. Fragment VIII-C can be activated by thrombin in a similar manner to the coagulant activity of whole factor VIII. This activation is calcium-dependent. In rabbits immunized against purified F VIII, VIII-C and VIII-AG specific antisera against these three entities were obtained.
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PMID:[Dissociation of human factor VIII and recombination of the fragments VIII-C and VIII-AG]. 46 70

A comparative study on the coagulant activity of snake venoms was carried out in 26 Bothrops species, using specific clotting systems for the thrombin-like and the factor X-activator activities. With only two exceptions (B. erythromelas and B. castelnaudi) all venoms showed thrombin-like activity, since they were able to clot fibrinogen directly. The absence of thrombin-like action of B. erythromelas venom is due to a fibrinogenolytic effect. Five venoms (B. atrox asper, B. bilineatus bilineatus, B. cotiara, B. fonsecai and B. itapetiningae) were unable to produce a prothrombin activator when preincubated with serum, factor V, and phospholipid. None of the venoms seems to require factors VII, VIII, IX, XII and XIII for their complete coagulant action. Direct prothrombin activation was observed in most of the Bothrops venoms, alone or combined with thrombin-like and factor X-activator activities. An anticoagulant activity was exhibited by B. castelnaudi venom, probably due to an anti-Xa action. This study points out that the coagulant activity of snake venoms varies within the same genus and must be characterized for each species. Thus, in Bothrops venoms the thrombin-like and factor X-activator components are not always associated, the coagulant effect may be related only to one of the components.
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PMID:Thrombin-like and factor X-activator components of Bothrops snake venoms. 47 15

Evidence of developmental evolution of coagulation can be seen when the studies of 10 thriving extremely premature (EPT) infants are compared to normal full-term (FT) infants. The prothrombin time, partial thromboplastin time, and thrombin time all became shorter with increasing gestational age. Fibrinogen levels and platelet counts appear to be comparable to term infant and adult levels. Fibrin degradation products (FDP) of 10 micrograms/ml or less were found in the thriving EPT infants. When compared to healthy full-term infants, there is a definite gestational dependency of anti-thrombin III levels. Factors II and VII appear to be related to intrauterine maturation after the age of viability (24 wk), but factor VII-X complex does not. The contact factors XI, XII, high molecular weight kininogen (Fitzgerald factor), and prekallikrein (Fletcher factor) are all markedly decreased in thriving EPT infants. The mean factor V level is lower than that found in FT infants. This study confirms a gestational age dependency of factor VIII activity. The ratio of factor VIII antigen to factor VIII clotting activity is increased (2.8 vs 1.01 in FT and adults). Thriving small for gestational age (SGA) infants had coagulation studies which were not statistically different from those of thriving EPT infants. The coagulation changes which occurred in severely ill EPT were mainly in the factors which decrease during intravascular coagulation (factors I, V, and VIII). The present study suggests that because of the high antigen to activity ratio seen in thriving EPT infants, a dysfunctional or fetal factor VIII may have been produced. However, the further elevation of this ratio in the severely ill EPT infants is in keeping with a pathologic proteolysis or increased endothelial release of factor VIII antigen.
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PMID:Coagulation studies in extremely premature infants. 52 93


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