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)

Protein C is a vitamin-K dependent plasma protein, whose activation is catalyzed by alpha-thrombin. Unlike vitamin-K dependent coagulation factors, activated Protein C is an anticoagulant enzyme. Purpose of the present study was to evaluate the pathophysiology of Protein C in patients undergoing minor and major elective surgery. A third group of patients were operated for cancer of the gastrointestinal tract. Protein C levels have significantly decreased in all patients in third postoperative day, while this decrease occurred since the first postoperative day in the case of cancer patients. This suggests that Protein C is consumed after surgery in its anticoagulant and profibrinolytic activity. The acquired Protein C deficiency may be related to postoperative hypercoagulability and increased risk of deep vein thrombosis.
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PMID:Protein C: a new plasma protein related to postoperative hypercoagulability. 654 3

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

These studies describe an assay of whole blood clot lysis as measured by release of 125I-fibrinogen degradation products. Optimal rates of lysis were obtained at 37 degrees C in 10-12 mM EDTA or 3,8% citrate and 4 u of thrombin/ml. Eighteen normal subjects and eight patients (six with recurrent deep vein thrombosis, one with thrombasthenia, and one with hepatitis and resolving portal vein thrombosis) were studied using this assay. The clots of seventeen of the eighteen normal subjects were 50% lysed at 40 hours. The clots of the patients with venous thrombosis and thrombasthenia did not lyse whereas the clots of the patient with hepatitis, resolving portal vein thrombosis and a high plasminogen activator level (0.32 CTA units) were 100% lysed at 4.5 hrs.
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PMID:Observations on optimal conditions for lysis of whole blood clots and use of this assay as a screening assay in clinical investigation. 682 Jan 94

Antithrombin 3 (AT 3) is the most potent physiologic inactivator of thrombin and other serine proteases in the blood clotting mechanism. Hereditary deficiency of this protein is associated with recurrent deep vein thrombosis that begins in late adolescence. Untreated, this disease may lead to early death from recurrent and massive pulmonary emboli. Attempts to identify groups of patients most likely to develop thromboembolic disease because of an acquired deficiency of AT 3 have been frustrated by the lack of standardization of the assays and the inability to compare results of different AT 3 assays. The functional assays and immunoelectrophoretic determinations do not measure the same component. In order to compare the ability of current AT 3 procedures to determine levels of AT 3 in various disease states, we used immunoelectrophoretic, chromogenic, and clottable assays to measure AT 3 in patients with congenital AT 3 deficiency and with possible acquired AT 3 deficiency.
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PMID:A comparison of antithrombin III procedures. 688 70

A study is reported which tries to identify those members of the general population who may be at increased risk of vascular disease. It is probable that patients who have had previous thrombotic episodes are inherently more at risk of further episodes and that a thrombus many months ago will not affect current tests. Accordingly we carried out a number of tests involving platelets on 'controls', and on patients with a past history of either myocardial infarction or deep vein thrombosis (DVT) and patients suffering from intermittent claudication who also are assumed to be at higher risk than the controls. Differences were demonstrated between controls and patient groups and these differences were utilized to develop statistical functions with the ability to discriminate between the groups. The functions were then tested using a second set of data from similar groups. Those designed to discriminate between myocardial infarction patients and controls and between patients with claudication and controls were validated. The heparin thrombin clotting time was found to be the prime predictor variable; the platelet count, platelet volume, platelet factor 3 clotting time and the bleeding time have some predictive value. The antithrombin clotting time, platelet aggregation and platelet adhesiveness tests as measured were not found to have discriminating potential. It is suggested that these appropriate risk functions could be of practical value in identifying members of the general population who may be at greater risk than average. The discriminate functions for DVT patients and controls could not be validated, suggesting differences in platelet involvement in arterial and venous thrombosis.
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PMID:Platelets in the prediction of thrombotic risk. 715 92

In a randomized double blind clinical trial, we compared indobufen, an antiplatelet drug, with acenocoumarol for the prevention of deep venous thrombosis (D.V.T.) in patients with acute myocardial infarction. Therapy was started on admission and continued for 10 days. All patients were screened daily with impedance plethysmography (I.P.G.) and 125I-fibrinogen leg scanning. Diagnosis of D.V.T. was made when either one or both tests became positive. 74 patients were randomized to treatment with indobufen (200 mg b.i.d.) and 76 patients to acenocoumarol (controlled by thrombotest). The incidence of venous thrombosis in patients with indobufen was 11% and in those treated with acenocoumarol 9%. Major bleeding was observed in 2 patients treated with acenocoumarol. In the indobufen group, no bleeding complications or other serious side-effects were observed. The majority of patients developed thrombosis after the first week of admission. For patients with and without thrombosis, there was no significant difference between the two treatment groups concerning the age, the coronary prognostic index, the maximum C.P.K. value, mobility, incidence of congestive heart failure and the site or extent of the infarct. In this study no clinical or laboratory (fibrinogen, platelet count and anti-thrombin III) parameter, either alone or in combination, was of predictive value for the development of D.V.T. It can be concluded that indobufen appears to be as good as acenocoumarol for the prevention of D.V.T. in patients with acute myocardial infarction. Because it is safe and easy to administer, indobufen seems to be preferable. Prophylaxis is required for at least 10 days.
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PMID:The incidence of deep venous thrombosis in patients with an acute myocardial infarction treated with acenocoumarol or indobufen. 717 1

Streptokinase was infused for 103 +/- 25 hrs. in 27 patients (6 with deep vein thrombosis of the leg, 7 with thrombosis of Vv. axillaris and subclavia, 9 with acute massive pulmonary embolism, 3 with chronic artery occlusion, 2 with thrombosis of the retinal vein). Blood coagulation studies were performed repeatedly. Anticoagulation (prolongation of thrombin time to 1 1/2-2 1/2 of normal) could be achieved without additional heparin by reduction of streptokinase to doses as low as 20 000 U/h. Reptilase time correlated significantly with thrombin times. Following 24 hrs. of infusion, PTT was less than 50 sec. and Quick test less than 50% of normal in most instances. No correlation was found between PTT or Quick test and factor II, V, VI, X activities during streptokinase infusion. Bleeding was observed in 18 patients. The infusion was stopped because of bleeding in 3 cases. None of the coagulation tests performed in this study correlated with the incidence of bleeding. Hemoglobin concentration decreased 2,6 +/- 1,6 gr% and this decrease could no be explained by blood lesses.
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PMID:[Control of blood coagulation and complications in long-term streptokinase therapy]. 719 87

Prolonged infusion of streptokinase at the customary dose of 100 000 u/h results in undesired plasminogen depletion in many patients. This can be avoided by adaptation of the streptokinase maintenance dose to the presumed rate of plasminogen synthesis of each individual patient. The practicability of this approach was tested in 52 patients who had streptokinase therapy of 3 to 9 days duration for deep vein thrombosis. Twice daily measurements of thrombin time and fibrinogen concentration were performed for immediate clinical surveyance and dosage adjustments. These led to a change from the original 100 000 u/h in most patients: in 65% the dose was reduced and in 10% it was increased. By this measure excessive plasminogen depletion was avoided in 88% of the patients. In them the final maintenance dose ranged from 40 000 to 150 000 u/h. Side effects were similar to those reported for the standard dosage scheme, and clinical results were good with a phlebographic success rate of 91% in recent and 65% in subacute or chronic deep vein thrombosis.
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PMID:[Deep venous thrombosis: streptokinase treatment with adaptation of the maintenance dosage]. 741 3

The present trial was designed to comparatively investigate the pharmacokinetic profile and evaluate the apparent bioavailability pattern of three already marketed low molecular mass heparins (LMMHs): dalteparin (Fragmin), nadroparin (Fraxiparin), and enoxaparin (Lovenox) given by subcutaneous route. The study was carried out in 20 healthy young volunteers given, according to a cross over design, a single subcutaneous injection of the doses recommended for the prophylaxis of deep vein thrombosis (commercial preparations, prefilled syringes): dalteparin 2,500 IU (= 2,500 IU anti-Xa), nadroparin 7,500 ICU (= 3,075 IU anti-Xa), enoxaparin 20 mg (= 2,000 IU anti-Xa) and enoxaparin 40 mg (= 4,000 IU anti-Xa). Of the markers used, activated partial thromboplastin time (APTT), thrombin clotting time (TCT), Heptest, anti-thrombin (aIIa) activity and anti-Xa (aXa) activity, the most pertinent parameter (from a biodynamic viewpoint) is plasma aXa activity. We demonstrated that dalteparin, nadroparin and enoxaparin exhibit statistically significantly different pharmacokinetic and overall disposition patterns. Normalized to the same injected dose (1,000 IU aXa), the relative actual amount of plasma anti-Xa activity generated by enoxaparin is 1.48 times greater (p < 0.001) than that of nadroparin and 2.28 times greater (p < 0.001) than that of dalteparin while the plasma amount induced by nadroparin is 1.54 times greater (p < 0.001) than that of dalteparin. The apparent total body clearance of enoxaparin doses (CL/F = 16.7 +/- 5.5 and 13.8 +/- 3.2 ml/min) is significantly smaller than those of nadroparin (CL/F = 21.4 +/- 7.0 ml/min; p < 0.01) and dalteparin (CL/F = 33.3 +/- 11.8 ml/min; p < 0.001) while dalteparin apparent clearance is about 1.5-fold greater (p < 0.001) than that of nadroparin. These LMMHs also differ by their renal excretion pattern: more fragments exhibiting an anti-Xa activity are recovered in urine following enoxaparin doses (6.4 and 8.7% of the dose, respectively) than following nadroparin (3.9%) and dalteparin (3.4%) injection. These differences in the disposition profiles explain why the apparent elimination half life t1/2 values of the LMMHs compared here are different: dalteparin: 2.8 h; nadroparin: 3.7 h; and enoxaparin: 4.1 h. Whether or not these differences may contribute to explain the different safety/efficacy balance of each of these antithrombotic medications remains to be discussed and needs further studies.
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PMID:Comparison of the pharmacokinetic profiles of three low molecular mass heparins--dalteparin, enoxaparin and nadroparin--administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism). 749 71

Activation of prothrombin and the subsequent reactions of thrombin with its substrates and its major inhibitors, antithrombin III (AT III) and heparin cofactor II (HC II), likely reflect both intravascular and extravascular coagulation. Several studies have reported increased in vivo coagulation in cancer. Whether the increased thrombin production in malignancy is accompanied by a corresponding increase in thrombin inhibition is unknown. This study quantified prothrombin fragment 1 + 2 (F1 + 2), thrombin-AT III (TAT), thrombin-AT III-vitronectin (TAT.V), and thrombin-HC II-vitronectin (THCII.V) in the plasmas of healthy volunteers (n = 37); patients with localized solid tumours before treatment was initiated (n = 39); and five patients with non-Hodgkin's lymphoma, both before and during weekly chemotherapy. Two of the five non-Hodgkin's lymphoma patients developed deep venous thrombosis (DVT) during chemotherapy. In normal plasma, where the concentrations of the four parameters likely reflect haemostasis, the sum of TAT, TAT.V and THCII.V was 61% that of F1 + 2, compared with 30% in cancer plasmas. In addition, the mean +/- SEM of F1 + 2 in the plasmas of cancer patients (1.56 +/- 0.09 nM) was significantly elevated (P < 0.001) when compared with healthy volunteers (0.89 +/- 0.06 nM). Eight weeks of chemotherapy increased the F1 + 2 and the binary TAT in plasmas of the non-Hodgkin's lymphoma patients by approximately 1.5- and 2.9-fold, respectively. Thus, increased prothrombin activation in cancer patients, without corresponding increases in concentrations of thrombin-inhibitor complexes, raise the possibility that a significant portion of the thrombin generated in vivo escapes inhibition in cancer and contributes to the high risk of DVT in malignancy.
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PMID:The hypercoagulable state in cancer patients: evidence for impaired thrombin inhibitions. 751 51


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