Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Venous thrombo-embolism is a common complication in patients with acute ischaemic stroke. Without prophylaxis, deep vein thrombosis occurs in 60-75% of patients with dense hemiplegia, usually in the paralyzed limb, and 1-2% suffer fatal pulmonary embolism. Orgaran (Org 10172, low-molecular-weight heparinoid) has been evaluated for the prevention of deep vein thrombosis in patients with acute ischaemic stroke in two studies. In a double-blind study, 75 patients were randomized to receive Orgaran (50 patients) in a loading dose of 1,000 anti-Xa units intravenously followed by 750 anti-Xa units subcutaneously 12-hourly or placebo (25 patients). Deep vein thrombosis occurred in 2 of 50 (4%) in the Orgaran group and 7 of 25 (28%) in the placebo group (p = 0.005). The corresponding rates for proximal deep vein thrombosis were 0 and 16%, respectively (p = 0.01). There was one major haemorrhage in the treated group and one minor haemorrhage in the placebo group. In the second study, the safety and efficacy of Orgaran was compared with unfractionated heparin in the prevention of deep vein thrombosis in a double-blind randomized trial. Eighty-seven patients with marked lower limb paralysis secondary to stroke were randomized to receive Orgaran (45 patients) in a dose of 750 anti-factor Xa units subcutaneously 12-hourly or unfractionated heparin (42 patients) in a dose of 5,000 units subcutaneously 12-hourly. Venous thrombosis occurred in 4 of 45 (8.9%) of the Orgaran group and 13 of 42 (31%) in the unfractionated heparin group (2p = 0.014). The corresponding rates for proximal vein thrombosis were 4.4 and 11.9%, respectively (2p = 0.255).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Orgaran in the prevention of deep vein thrombosis in stroke patients. 137 69

Heparin clearance and pharmacodynamic response were examined in 12 patients being treated for deep venous thrombosis (DVT, 6 patients) or pulmonary embolism (PE, 6 patients). A loading dose of 70 units/kg was administered to DVT patients and 100 units/kg to PE patients followed by an initial infusion rate of 15 or 25 units/kg/h for DVT or PE patients, respectively. Heparin clearance was determined at 4, 12, and 24 h after initiating heparin therapy. The mean heparin clearance in the DVT group was 2,164 +/- 1,024 ml/h at 4 h, 2,591 +/- 1,239 ml/h at 12 h, and 2,795 +/- 1,863 m/h at 24 h. The PE patients had clearances of 1,775 +/- 494, 2,004 +/- 321, and 2,843 +/- 1,000 ml/h at 4, 12, and 24 h, respectively. The difference between the two groups was not statistically significant (p greater than 0.50). The activated partial thromboplastin time (aPTT) was used as a measure of heparin effect. The maximum effect (EMAX) and concentration required to attain 50% of the maximum effect (EC50) were determined for each group using the Lineweaver-Burke linearization method. The mean EMAX and EC50 for the DVT patients were 130 +/- 40.99 s and 1.01 +/- 0.70 units/ml, respectively. For the PE patients, the mean EMAX was 418 +/- 200 s and the mean EC50 was 4.32 +/- 2.81 units/ml. The difference between both groups for each parameter was statistically significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered heparin pharmacodynamics in patients with pulmonary embolism. 144 41

To assess the incidence, risk factors, and clinical importance of deep vein thrombosis in acute stroke, we studied 70 consecutive patients who underwent hemostasis screening at the time of entry into the study and followed up these patients with serial venous Doppler examinations and the iodine 125-labeled fibrinogen uptake test. Mortality was significantly higher among the 20 patients who developed a deep vein thrombosis, and eight of them had necropsy evidence of pulmonary embolism. Severity of leg paresis and a shortened activated partial thromboplastin time were significantly associated with subsequent deep vein thrombosis with multivariate analysis. Significantly higher levels of fibrinopeptide A were found in patients with postmortem evidence of pulmonary embolism. Deep vein thrombosis is a frequent complication of acute stroke and may influence the prognosis by inducing pulmonary embolism. Our findings allow rapid identification of high-risk patients who may benefit maximally from prophylactic treatment of venous thromboembolism.
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PMID:Venous thromboembolism in acute stroke. Prognostic importance of hypercoagulability. 153 31

Fine-needle aspiration (FNA) of the liver is a procedure considered virtually risk-free. We report here a patient with carcinoma of the pancreas, who suffered a fatal hemoperitoneum (HP) subsequent to FNA of the liver under the guidance of ultrasound. The patient had presented with migratory deep vein thrombosis (DVT), and recurrent cerebral embolism. The prothrombin time (PT) and partial thromboplastin time (PTT) had been normal, and FNA demonstrated adenocarcinoma cells. Autopsy findings demonstrated carcinoma in the tail of the pancreas with liver and adrenal metastases, massive HP, and findings of chronic disseminated intravascular clotting (DIC). Since chronic DIC with enhanced fibrinolysis might have participated in the fatal bleeding, we recommend that FNA should be contraindicated in patients suspected of having malignancy with migratory DVT and recurrent arterial embolism, despite normal PT and PTT tests, unless the appropriate laboratory tests succeed in excluding DIC.
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PMID:Fatal hemoperitoneum after fine-needle aspiration of a liver metastasis. 153 72

Thrombolytic therapy is rarely used in venous thromboembolism because of the fear of hemorrhagic complications. Preliminary clinical experiences with recombinant tissue-type plasminogen activator (rt-PA) in patients with deep vein thrombosis have shown that even this fibrin-specific plasminogen activator causes an unacceptable rate of hemorrhagic complications. Theoretical considerations and the available experimental and clinical data suggest that infusion of rt-PA over a short period of time would result in a more favorable risk-benefit ratio. Shortening the period of rt-PA infusion results in higher peak plasma levels, thus allowing a higher concentration of the plasminogen activator on the surface and inside the occluding thrombus. In addition, a bolus infusion can prevent or minimize the interaction between rt-PA and the hemostatic system, reducing the likelihood of a systemic lytic state, of a platelet function defect, and, possibly, of bleeding side effects. In venous thromboembolism animal models, the efficacy of bolus rt-PA can be further increased by the adjunctive administration of an effective antithrombotic treatment. This is because the accretion of new fibrin on the thrombi counteracts the lysis of preformed fibrin and influences negatively the final thrombus size. Effective adjunctive antithrombotic treatment includes either high doses of heparin, producing an unclottable activated partial thromboplastin time (aPTT), or doses of recombinant hirudin, doubling the aPTT. When used as an alternative to rt-PA, bolus doses of a hybrid plasminogen activator with prolonged half-life efficiently reduce thrombus size by lysing preformed and newly formed fibrin. Preliminary clinical experience in patients with pulmonary embolism seems to confirm that rt-PA infused as a bolus is at least as effective as, and probably more effective than, rt-PA infused over a longer period.
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PMID:Bolus thrombolysis in venous thromboembolism. 155 82

An inherited deficiency of protein C, a recognized hypercoagulable state, may cause a clinically significant deep venous thrombosis. Only some persons with a deficiency of protein C experience thrombosis, and almost always the thrombotic event occurs in the venous circulation. Warfarin-induced skin necrosis, a rare event observed in some patients soon after treatment with warfarin is begun, is believed to be another manifestation of this deficiency. We describe a young woman whose basal functional and antigenic levels of protein C were about 45% and who experienced both deep venous thrombosis and warfarin-induced skin necrosis in a clinically severe course. Evidence for lupus anticoagulants was present, with prolonged activated partial thromboplastin time that was corrected when lysed platelets were added, prolonged Russell's viper venom time, anticardiolipin antibodies, and other laboratory evidence. Lupus anticoagulants are associated also with a significant incidence of thrombosis, including arterial thrombosis, and this patient developed concurrently arterial thrombosis. The combined effects of protein C deficiency and lupus anticoagulants, exacerbated by other potentially thrombogenic conditions, are believed responsible for the severe thrombotic events experienced by this patient.
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PMID:Concurrent protein C deficiency and lupus anticoagulants. 156 44

We are reporting a young lady with protracted deep vein thrombosis of her left leg which turned out to be antiphospholipid (anticardiolipin) antibody syndrome of ANA positive systemic lupus erythematosus. Lupus anticoagulant was demonstrated by prolongation of activated partial thromboplastin time and Russell's viper venom time. She had no anti-thrombin III deficiency.
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PMID:Antiphospholipid antibody syndrome of systemic lupus erythematosus presenting as deep vein thrombosis. 829 83

The D-Dimer (D-D) assay for measuring cross-linked fibrin degradation products is now available for the clinical laboratory. We combined this assay with other tests to assess patients with diagnosed or suspected DIC. Also, a small group of patients (20) with deep venous thrombosis (DVT) were studied. The D-D test, antithrombin-III assay, FDP titer, fibrinopeptide-A level, protamine sulfate test, fibrinogen, prothrombin time, and activated partial thromboplastin time were used. The D-D test was abnormal in 93.7%, the AT-III level was abnormal in 87.5%, the fibrinopeptide-A level was abnormal in 89.5%, and the FDP titer was elevated in 83.7% of patients with DIC. When assessing patients found not to have confirmed DIC the D-D assay was abnormal in 20%, the AT-III level was abnormal in 6%, and the fibrinopeptide-A level was elevated in 13%. We conclude the D-Dimer assay to be a useful molecular marker of hemostasis in diagnosing DIC and this test will often discriminate between those patients with or without DIC, especially when used with the AT-III and fibrinopeptide-A assays. Of the battery of tests used in this study, the most useful, in descending order of efficacy, appear to be the D-dimer assay (93.7% abnormal), the fibrinopeptide-A titer (89.5% abnormal), the AT-III level (87.5% abnormal), and the FDP titer (83.7% abnormal). Of the global tests, the diagnostic efficacy of the prothrombin time activated partial thromboplastin time, and protamine sulfate test were no greater than chance and appear to be of little use in aiding in a diagnosis of DIC. Also, the D-Dimer assay is similar in cost to the FDP titer and is cost effective for the routine clinical laboratory.
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PMID:Diagnostic efficacy of the D-dimer assay in disseminated intravascular coagulation (DIC). 163 67

The standard treatment of deep vein thrombosis is given by continuous intravenous infusion of unfractionated heparin. This entails hospitalisation, nursing care, immobility and repeated laboratory tests (e.g. activated partial thromboplastin time [APTT], platelet count). In addition approximately 10% of patients suffer major haemorrhages. The potential advantages of a low molecular weight heparin (CY 216) given subcutaneously were explored in a randomised trial with blind quantitative evaluation of venograms. The study included 166 patients and both "therapeutic efficacy" and "intention to-treat" analyses showed that subcutaneous CY 216 in fixed doses based only on body weight was more effective on the Arnesen and Marder phlebographic scores than continuous i.v. standard heparin with daily dose adjustment according to results of coagulation tests. There was no increase in the risks of pulmonary embolism, haemorrhage or clot extension.
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PMID:A randomised trial of subcutaneous low molecular weight heparin (CY 216) compared with intravenous unfractionated heparin in the treatment of deep vein thrombosis. A collaborative European multicentre study. 164 90

The depolymerisation of the various chains of unfractionated heparin (UFH) by chemical or enzymatic reactions provides so-called low molecular weight heparin (LMWH), with an average molecular weight of approximately 5000 daltons. The specific biological and pharmacokinetic properties of LMWH with greater inhibition of factor Xa than of thrombin activity, less interaction with platelets, better bioavailability and a longer half life of anti-Xa activity, suggest possible new therapeutic applications. The hypothesis of reducing the risk of haemorrhage related to the antithrombin activity and the incidence of heparin-induced thrombocytopenia whilst preserving effective antithrombotic action has stimulated clinical and biological research. Clinical trials of prophylaxis of venous thrombo-embolism have been undertaken mainly in surgical patients. The results have shown identical if not better efficacy of LMWH compared to UFH in general surgical and above all orthopedic patients in whom subcutaneous heparin is only effective with a strict protocol which is difficult to adhere to in routine practice (adaptation of dosage to activated partial thromboplastin time). The risk of bleeding was not significantly lower using LMWH at the specified dosage, which in the latter indication, is twice that used in general surgery. There are many indications of prophylaxis of thromboembolism in the medical specialties but, paradoxically, LMWH has not been widely studied because of the difficulties in performing the therapeutic trials. Except in rare cases (extreme body weights, renal failure, haemorrhagic disease, thrombotic or haemorrhagic complications) the evaluation of amidolytic anti-Xa activity does not seem to be necessary. More recently, LMWH has been studied in a small number of trials for the treatment of deep venous thrombosis (DVT). The therapeutic efficacy is identical if not better than that of UFH without increasing the risk of bleeding. Biological monitoring seems to be necessary in this indication for evaluating amidolytic anti-Xa activity, which, though not a true marker of antithrombotic activity is a relatively sensitive investigation. The therapeutic values are 0.5 IU/ml to 1.0 IU/ml, 3 to 4 hours after subcutaneous injection. The conclusions of all these trials are: LMWH is relatively simple to use and, compared with UFH, has a more stable anticoagulant effect due to its pharmacokinetic properties; the therapeutic efficacy is as good as, if not better, than that of UFH; the risk of bleeding remains, therefore, the specified dosages should be respected and treatment should be monitored by anti-Xa activity when indicated; the decreased interaction with platelet function should not mask the risk of thrombocytopoenia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Therapeutic indications of low molecular weight heparins]. 166 41


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