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)

Factor VIII antigen (VIII:CAg) exhibits molecular weight heterogeneity in normal plasma. We have compared the relative quantities of VIII:CAg forms present in normal individuals (n = 22) with VIII:CAg forms in renal dysfunction patients (n = 19) and in patients with disseminated intravascular coagulation (DIC; n = 7). In normal plasma, the predominant VIII: CAg form, detectable by sodium dodecyl sulfate polyacrylamide gel electrophoresis, was of molecular weight 2.4 X 10(5), with minor forms ranging from 8 X 10(4) to 2.6 X 10(5) D. A high proportion of VIII:CAg in renal dysfunction patients, in contrast, was of 1 X 10(5) mol wt. The patients' high 1 X 10(5) mol wt VIII: CAg level correlated with increased concentrations of serum creatinine, F1+2 (a polypeptide released upon prothrombin activation), and with von Willebrand factor. Despite the high proportion of the 1 X 10(5) mol wt VIII:CAg form, which suggests VIII:CAg proteolysis, the ratio of Factor VIII coagulant activity to total VIII:CAg concentration was normal in renal dysfunction patients. These results could be simulated in vitro by thrombin treatment of normal plasma, which yielded similar VIII:CAg gel patterns and Factor VIII coagulant activity to antigen ratios. DIC patients with high F1+2 levels but no evidence of renal dysfunction had an VIII:CAg gel pattern distinct from renal dysfunction patients. DIC patients had elevated concentrations of both the 1 X 10(5) and 8 X 10(4) mol wt VIII:CAg forms. We conclude that an increase in a particular VIII:CAg form correlates with the severity of renal dysfunction. The antigen abnormality may be the result of VIII:CAg proteolysis by a thrombinlike enzyme and/or prolonged retention of proteolyzed VIII:CAg fragments.
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PMID:Abnormal factor VIII coagulant antigen in patients with renal dysfunction and in those with disseminated intravascular coagulation. 393 66

The biologic activity of Factor XIII was measured in four groups of patients: 20 with liver cirrhosis, ten with acute DIC, 30 with acute leukemia with DIC, and 20 with acute leukemia without DIC. In all groups, the plasma Factor XIII transamidating activity was reduced, but this deficiency was more evident in patients with DIC alone or with leukemia and DIC. The immunologic determination of the a and b subunits of Factor XIII was also performed. Both subunits were below the normal range in the groups of patients studied, except for subunit b, which was normal in patients with leukemia without coagulopathy. Acute DIC patients showed an equally reduced level of both subunits, whereas in patients with leukemia, even in the presence of a complicating coagulopathy, a lesser decrease of subunit b than subunit a was found. Both subunits were equally reduced in patients with cirrhosis, suggesting an impaired synthesis of these proteins. In conclusion, our findings do not support the use of Factor XIII subunit measurements in distinguishing between thrombin- or protease-mediated consumption coagulopathy, and they seem to suggest that the deficiency pattern of the subunits is not accounted for by a simple pathogenetic mechanism.
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PMID:A contribution to the pathology of acquired plasma factor XIII deficiency. 407 Oct 61

Effect of thrombin and endotoxin on the metabolism of I-125-labelled canine AT III was studied in mongrel dogs. Under control condition, mean total amount of intravascular AT III with standard deviation was 23.4 +/- 2.4 mg/kg, plasma half life of i.v. injected I-125-AT III was 1.7 +/- 0.2 days, and the fractional catabolic flux (j3x) was 16.3 +/- 1.6 mg/kg/day. The total amount of intra- and extra-vascular AT III was 36.0 +/- 0.34 mg/kg. Neither a 3 hour infusion of a small dose (30 units/kg/hr) of thrombin nor i.v. injection of a large amount of thrombin (5,000-15,000 units/day) with heparin significantly affected AT III metabolism except for a transient decrease in AT III concentration in the latter case, although decrease in plasma fibrinogen concentration and platelet count was observed in both cases. Two injections with 200 micrograms/kg of endotoxin resulted in an evident acceleration of AT III metabolism with significant decrease in the plasma AT III, fibrinogen concentrations and platelet count. More marked changes in AT III metabolism were induced by a single infusion with 1 mg/kg of endotoxin. Changes in hemostatic system coincided with those observed in DIC.
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PMID:Effect of thrombin and endotoxin on the in vivo metabolism of antithrombin III (AT III) in dogs. 408 11

FPA, although identified 15 years ago, is now becoming an increasingly important diagnostic tool in the evaluation of the hemostatic process. Since this peptide is generated in very small amounts, only very sensitive methods, such as RIA, are useful for its quantitation. Measurement of this peptide allows for a most precise and reliable monitor of any ongoing thrombotic event in which thrombin is generated. Commercial kits have become available for fast and simple clinical evaluations of FPA. The Mallinckrodt RIA Quanti FPA kit has proved its reliability in precision, accuracy, fast turnaround time, and applicability to a routine laboratory setting. This assay kit was evaluated in our laboratory in various aspects. The following points summarize our finding: FPA is a useful diagnostic parameter to evaluate the activation of coagulation pathways in various pathologic states. A study of 170 normal plasma samples resulted in 1.7 +/- 0.5 ng/ml. No significant difference between males and females was noted. FPA levels are evaluated in patients with hypercoagulable states, DIC, and related thrombotic states. Our studies have shown that FPA levels are also elevated in certain cancers, postsurgical states, and certain other conditions in which the coagulation process is activated. During therapeutic heparinization, FPA levels are reduced; thus this form of therapy can be monitored using FPA levels. High-risk population (thrombotic) can be easily screened using FPA measurement. We propose that a multicenter study on FPA levels be conducted to prove its clinical relevance to other diseases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Performance characteristics of a simple radioimmunoassay for fibrinopeptide A. 651 18

An assay measuring the thrombin inactivating effect of human plasma in the presence of dermatan sulfate (DS) is described. Test plasma, diluted 1/50, is incubated with human thrombin in the presence of DS. Remaining thrombin is determined with chromogenic substrate 2AcOH . H-D-CHG-Ala-Arg-pNA. Three dilutions of reference plasma suffice and the standard curve is linear. Antithrombin III (AT) exerts a small (3-8%) effect in the assay. When test plasma contains heparin above 0.05 U/ml, this unspecific effect of AT increases, but it may be abolished by antibodies against AT. In a normal material (n = 50), the SD of DS cofactor activity was greater (15%) than that of AT (8.7%). DS cofactor was normal in hereditary AT deficiency and in 15 patients with deep venous thrombosis. In liver cirrhosis and in DIC, both inhibitors were markedly depressed, to similar degrees (r = 0.84).
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PMID:Assay of dermatan sulfate cofactor (heparin cofactor II) activity in human plasma. 654 86

A computer analysis of the coagulation laboratory records at the first department of Hokkaido University Hospital over a three-year period (1979-1981) was performed on 553 patients with presumptive intravascular coagulation. It is indicated that the most important diagnostic tests for DIC were Fbg, FDP, and AT III. DIC may have developed not only in patients with reduced Fbg but also in patients with normal or elevated Fbg. It is necessary to estimate the actual situations in the patients with DIC by utilizing sequential laboratory tests. In DIC, SDS-PAGE patterns of Fbg indicated the marked reduction of LMW Fbg, and the activated fibrin formation must be caused by the high affinity of thrombin for HMW Fbg. Changes in the immunoprecipitative second peak of AT III may indicate the binding of different serine proteases to AT III in DIC. Rapid and simple diagnostic tests for DIC are clinically required. An analysis of the TEG pattern using normal plasma mixed with the patient's plasma can indicate the presence of procoagulant activity in patient plasma. Such a laboratory test using TEG is the most useful and rapid diagnostic test in DIC. An anticoagulant effect of heparin therapy is determined by APTT and heparin levels. The antithrombotic effect of heparin therapy is determined by FPA as an immediate index and by Fbg, FDP, and AT III as a slow index.
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PMID:Estimation of coagulation-fibrinolytic factors in DIC. 666 45

The effects of Russell's viper venom on blood coagulation, platelets and the fibrinolytic enzyme system were studied in rabbits after injecting repeated doses of 0.05 MLD of the venom. Thrombocytopenia was the earliest change to appear. It was followed by rise in serum fibrinogen degradation products and prolongation of prothrombin time, activated partial thromboplastin time and thrombin time indicating a progressive consumption coagulopathy and activation of fibrinolysis. Red blood cell morphology was unchanged during the first three weeks; whereas the fragmentation appeared after the fourth week and it increased in severity with further envenomations, i.e. when chronic DIC was established.
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PMID:Effects of prolonged poisoning by Russell's viper venom on blood coagulation, platelets and fibrinolysis. 673 75

In summary, this series of 48 patients with acute and chronic DIC demonstrates the reliability of laboratory tests in both aiding a diagnosis of DIC and in offering reasonable predictability of efficacy of therapy, as noted by the correction of abnormalities after delivery of antiprocoagulant therapy for this syndrome. It appears that the diagnostic tests most likely to aid in diagnosis and to reliably inform the clinician when the intravascular clotting process has been stopped are those that determine the antithrombin-III level, the presence of soluble fibrin monomer, and the finding of elevated fibrin(ogen) degradation products, thrombocytopenia and a prolonged thrombin time in the face of the appropriate type of bleeding in the appropriate clinical setting. In addition, it would appear that mini-dose heparin therapy is highly effective in controlling the intravascular clotting process in acute DIC, whereas antiplatelet therapy utilizing two agents is effective in chronic DIC. In addition, in this population, patients with acute disease demonstrated a 74 percent survival rate and those with chronic disease had a 100 percent survival rate from the disseminated intravascular clotting process.
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PMID:Disseminated intravascular coagulation: a clinical/laboratory study of 48 patients. 694 79

Coagulation profiles were performed in 30 consecutive alcoholic cirrhotic patients without known infection, malignancy, recent surgery, transfusion, or alcoholic intake. Hemorrhagic phenomena were present in 70% and included gastrointestinal bleeding, oozing from venipuncture sites, bruising, and epistaxis. All 30 patients had multiple liver function and coagulation abnormalities, the most frequent of which were increases in F VIII components and decreases in F XI and F VII. Also decreased in half or more of the 30 patients were Fletcher F, F II, F X, prothrombin time (PT), partial thromboplastin time (APTT), thrombin time (TT), reptilase time (RT), anti-thrombin III, and plasminogen. When comparing cirrhotic bleeders with nonbleeders, four parameters were significantly different in those with a bleeding tendency: F VII, anti-thrombin III, plasminogen, and albumin. The prolonged APTT was associated in four cases with a blocking inhibitor of unknown etiology. The prolonged TT and RT, in the absence of fibrin split products, fibrin monomers, DIC, or shortened euglobulin lysis time in any patient were suggestive of an abnormal fibrinogen, a dysfibrinogen. In three other patients, there was an inhibitor of the TT. Further investigation of the suspected dysfibrinogen in 21 patients by SDS-polyacrylamide gel electrophoresis revealed that the molecular weights of the Aalpha, Bbeta, and gamma polypeptide chains of fibrinogen were not different from normal. Two-dimensional immunoelectrophoresis of the suspected dysfibrinogen was similar to normal in 18 of 21 patients, with loss of the initial shoulder in three.
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PMID:Bleeding and coagulation abnormalities in alcoholic cirrhotic liver disease. 704 81

Plasma fibronectin (FN) binds fibrin in vitro by both noncovalent and covalent bonds and is decreased in DIC. In rabbits, conventionally purified 125I-FN had a complex blood clearance with a late t1/2 of 71 hr. A large portion was apparently altered, as evinced by rapid clearance and an intravascular/total body ratio (C1) of 0.28-0.51. 3H-labeled FN, made in vivo by injection of 3H amino acids, had a t1/2 of 73 hr. Crosstransfusion of 131I-FN and 3H-FN into a second set of animals gave similar t1/2s and C1s of 0.74-0.82, indicating the altered 125I-FN was biologically screened in the first animals. Other animals were given 125I-fibrinogen and "screened" 131I-FN. Intravenous thrombin (50-60 U/kg/1 hr) caused a 25%-50% decrease in both 125I-fibrinogen and 131I-FN. Ancrod injection reduced fibrinogen by greater than 90% but had no effect on 131I-FN. 131I-FN levels did not change when thrombin was given after ancrod. No cross-linked FN-fibrinogen alpha-chain was found in the plasma, nor was the thrombin-induced fall in FN affected by spermidine blockade. These experiments demonstrate that FN and fibrin bind in vivo during defibrination and are rapidly cleared from the blood. The abnormal fibrin resulting from ancrod either does not bind FN in vivo or does so reversibly.
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PMID:Fibronectin: blood turnover in normal animals and during intravascular coagulation. 710 86


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