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

This study reports the correlation of the thrombin generation test and the plasma clot impedance test with clinical evidence of hypercoagulability. Thrombin generation is increased and the rate of change of plasma from a liquid to a gel (clot impedance) is increased in situations where the risk of thrombosis is increased. These situations include increasing clinical signs and/or symptoms of thromboembolism, positive lung scans, postoperative total hip replacement, patients over 40 years old, low serum antithrombin III, thrombocytosis, transient cerebral ischemia, and positive isotope venogram for thrombosis. The two tests failed to indicate a significant effect of antiplatelet drugs on the hypercoagulable state. This study shows that the thrombin generation and plasma clot impedance tests are practical, rapid and useful tests for the detection and monitoring of the hypercoagulable state.
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PMID:Evaluation of the in vitro detection of the hypercoagulable state using the thrombin generation test and plasma clot impedance test. 50 79

A two-dimensional immunoelectrophoretic method has been used to obtain information on the binding of heparin to purified antithrombin III and the antithrombin III--thrombin complex. The difference in mobility of the components in a gel containing heparin enables distinction between free and complexed forms of antithrombin III. The results obtained with purified preparations show that heparin is bound more strongly to antithrombin III than to the antithrombin III--thrombin complex. In plasma heparin is bound to several components, only a fraction being bound to antithrombin III. Several components containing antithrombin III are detectable in serum.
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PMID:Crossed immunoelectrophoresis as applied to studies on complex formation. The binding of heparin to antithrombin III and the antithrombin III--thrombin complex. 55 71

Studies were conducted to determine the effect of modifying specific functional groups of heparin on its antithrombin III-enhancing activity. The derivatives employed were heparin methyl ester, heparinylglycine and N-desulfated heparin. The carboxyl-modified derivatives increase the rate of inhibition of thrombin by antithrombin III, although not to the same extent as heparin. N-Desulfated heparin is devoid of any activity. Heparin methyl ester is more potent than heparinylglycine in activating antithrombin III, as exhibited by its immediate effect on the thrombin-fibrinogen reaction. However, heparinylglycine is the more effective of the two, in increasing the rate of thrombin deactivation by antithrombin III. The results indicate that although free carboxyl groups of heparin are not crucial for its binding to antithrombin III, they are important for the combination of the latter with thromobin. In contrast, N-sulfates are critical for the interaction of heparin with antithrombin III.
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PMID:Effect of heparin modification on its activity in enhancing the inhibition of thrombin by antithrombin III. 56 Feb 16

Inhibition of the esterase and amidase activities of bovine alpha- and beta-thrombin in the presence of antithrombin III and heparin has been studied. It was found that both the esterase and amidase activities of alpha-thrombin were inhibited by antithrombin III and the reactions were accelerated by heparin. The inhibition of amidase and esterase activities of beta-thrombin by antithrombin III has also been demonstrated. Heparin however did not increase the rate of inactivation of the enzyme.
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PMID:Inhibition of esterase and amidase activities of alpha- and beta-thrombin in the presence of antithrombin III and heparin. 57 Apr 23

The inhibitory capacity of antithrombin III (AT III) was measured by a quantitative method independent of the velocity of inhibition. When AT III was in excess of thrombin in plasma or in purified system the capacity of inhibitor decreased quantitatively in proportion to the amount of thrombin neutralized. Heparin present in reaction together with thrombin invariably induced a more extensive utilization of inhibitor than thrombin alone. The extent of this additional loss of inhibitory capacity was to a limited degree related to the concentration of heparin. Heparin itself was neutralized in thrombin-AT III reaction losing its anticoagulant property in proportion to the amount of thrombin bound by inhibitor. This quantitative neutralization of heparin occurred not only when the anticoagulant participated in thrombin-AT III binding but also when heparin was added to a medium containing a preformed thrombin-AT III complex. These results suggest that acceleration of binding and increased utilization of binding capacity are the two regular effects of heparin on thrombin-involving reactions of AT III. Both of these effects may be abolished by quantitative binding of heparin to thrombin-AT III complex.
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PMID:Antithrombin III and heparin inactivation in thrombin involving reactions. 57 90

Plasma from 14 patients with severe and diffuse coronary atherosclerosis has been compared with that obtained from a normal control group. While a decreased heparin-thrombin clotting time was demonstrated in the patient group, suggesting an increased level of circulating platelet factor 4, there was no significant alteration in plasma antithrombin III level. These results do not support a recent suggestion of a mild chronic intravascular coagulation in atherosclerosis.
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PMID:Heparin neutralizing activity (HNA) and antithrombin III in coronary artery disease. 57 15

In 12 vascular and 17 trauma cases the changes in the coagulation system due to intraoperative autotransfusion (IAT) were examined immediately after the IAT as well as 24, 48, 72 h and one week later. The following parameters were monitored: 1. Platelet count. --2. Prothrombin-time, partial-thromboplastin-time, factors II, V, VII, X and thrombin-clotting-time. --3. Fibrinogen, alpha-1-antitrypsin, alpha-2-macroglobulin, antithrombin III and plasminogen in 5 trauma cases. --4. Euglobulin-Lysis-Time. --After the IAT a loss of platelets, factors I, II, V, X, plasminogen and antithrombin III was found. Alpha-1-antitrypsin and alpha-2-macroglobulin remained unchanged or showed a slight increase. 24 h after treatment with Ugurol and heparin, fresh frozen plasma, fibrinogen and Cohn I-fraction in selected cases, an increasing normalisation of most parameters was seen, except for the plasma proteins active in coagulation. They showed a combination of "consumption coagulophathy" and "hyperfibrinolysis" up to the 7th day. Under treatment outlines above even marked laboratory changes remained without any clinical significance. Thus our results confirm that IAT does not cause any additional irreversible damage to the coagulation system. Therefore IAT can be considered as method of choice for the emergency treatment of massive bleeding.
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PMID:[Intraoperative autotransfusion and its influence on the blood-clotting-system (author's transl)]. 59 9

The anticoagulant effect of heparin in test systems composed of purified factors [antithrombin III (AT-III), fibrinogen and thrombin] was studied. As expected, the sensitivity to heparin depended on the concentrations of AT-III and thrombin, whereas the fibrinogen level was less decisive. In addition, qualitative differences proved important. Thus, the sensitivity to heparin was greater with crude bovine thrombin than with highly purified thrombin from the same species. Further, the sensitivity to heparin increased following removal of cold-insoluble material from the fibrinogen preparation. Finally, during storage of purified AT-III at +4 degrees C for more than 4 weeks, the sensitivity to heparin decreased more rapidly than expected from the amidolytic AT-III assays. Smaller amounts of heparin were required to give a prolonged thrombin clotting time than in whole plasma, indicating that components of normal platelet-poor plasma (besides AT-III and fibrinogen) interfere with the anticoagulant effect of heparin. The present test systems may prove suitable for the detection and evaluation of factors of importance for the so-called heparin tolerance.
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PMID:The anticoagulant effect of heparin + antithrombin III using purified fibrinogen as substrate. 61 Oct 46

The effect on the heparin thrombin clotting time (HTCT) of a so-called acute phase protein, alpha1-acid glycoprotein, was studied in test systems consisting of purified fibrinogen, antithrombin III, heparin and thrombin, and compared to the effect of platelet material (crude platelet factor 4). In these test systems a physiological concentration of alpha1-acid glycoprotein (1 g/l) inhibited heparin more effectively than did soluble platelet material from 200 X 10(9) platelets/l. The present observations suggest that alpha1-acid glycoprotein is of great significance for the so-called heparin tolerance, whereas platelet material proved less important.
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PMID:The antiheparin effect of alpha1-acid glycoprotein and platelet material, evaluated by the heparin thrombin clotting time. 61 Oct 47

Human antithrombin III was found to contain covalently linked N-acetylglucosamine, mannose, galactose, and sialic acid in a molar ratio of approximately 1:1:0.6:1. Sialic acid was released upon treatment with neuraminidase. The modified glycoprotein retained the capability to inhibit thrombin and to bind with heparin. Antithrombin III isolated by different procedures was also found to contain glucose in an approximately equimolar ratio with N-acetylglucosamine. Th" glucose-containing component was extractable with lipid solvents and shown to be beta-glucosylceramide. This glycolipid is tightly complexed with antithrombin III and could not be separated by fractional precipitations or ion exchange gels. Although it remains to be established whether the inhibitory actions of antithrombin III are affected by glucosylceramide, the relative amounts which are bound suggest that antithrombin III may be a significant carrier of the glycolipid.
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PMID:Human antithrombin III. Carbohydrate components and associated glycolipid. 61 63


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