Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormal increase of erythrocyte aggregation and reduction of profibrinolytic activity are the two most frequent biological perturbations found in chronic venous insufficiency (CVI). A randomised, controlled, double blind trial was undertaken on 85 patients suffering from grade 1 and 2 CVI, to compare troxerutin with placebo. Two types of biological parameters were measured after 15 days of treatment. Erythrocyte aggregation as evaluated with a Myrenne erythroaggregometer by the indices M (stasis) and M1 (3s-1) progressed favorably in the troxerutin group. The values of M1 at D15 (p < 0.05), and the progression of M (p < 0.001) and M1 (p < 0.01) from D0 to D15, are significantly better in the troxerutin group. Progression of fibrinolytic activity at rest was not significantly different between the 2 groups. Conversely, the progression from D0 to D15 of the values after occlusion of euglobulin lysis time (p < 0.01), tPA (p < 0.01), and PAI activity (p < 0.05) are significantly better in the troxerutin group. The fibrinolysis capacity estimated by euglobulin lysis time (p < 0.01) and tPA (p < 0.05) also progressed favorably in the troxerutin group. These results confirm the anti-erythrocyte aggregation effect of troxerutin, and suggest a favorable effect on blood fibrinolytic activity. They could explain the positive action of this drug on stasis, capillary perfusion and trophic complications of CVL.
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PMID:Fibrinolysis and hemorheology in chronic venous insufficiency: a double blind study of troxerutin efficiency. 759 49

During the last 10 years anticoagulant (AC) therapy and thrombolytic treatment of venous thromboembolism (VT) have been evaluated in randomized studies. Adjusted subcutaneous (s.c.) heparin and low molecular weight heparin (LMWH) are found at least as effective as intravenous (i.v.) infusion of heparin in deep venous thrombosis (DVT) without an increased bleeding risk. In pulmonary embolism (PE) randomized trials assessing the efficacy of s.c. heparin and LMWH are missing. Oral AC-treatment can be initiated from the first or second day in VT. The recommended duration is three months for medical patients, and 4 weeks seem appropriate for surgical patients that are completely mobilized and without persisting predisposing factors. Long-term efficacy of thrombolytic treatment of DVT has only been assessed in small trials showing a trend towards reduced risk of developing chronic venous insufficiency. Short-term thrombolytic treatment of DVT is evaluated in ongoing trials. In the treatment of PE short-term thrombolysis with either t-PA or urokinase is found to be as effective as long-term thrombolytic treatment with a reduced bleeding risk. Thrombolytic therapy rapidly reduces embolic mass and stabilizes haemodynamics, but mortality and long-term efficacy of thrombolysis and AC-treatment versus AC-treatment alone in PE are being assessed in ongoing studies.
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PMID:[Anticoagulant and thrombolytic therapy in deep venous thrombosis and pulmonary embolism]. 778 97

Twenty-six patients with venous insufficiency and 15 normal controls were studied by local skin pathological and ultrastructure changes. Transcutaneous oxygen tension (Tcpo2) and tPA, PAI of venous blood were measured. Biopsies from the ulcerating and liposclerosis area showed pericapillary fibrins. The patients with severe venous disease resulting in liposclerosis or ulceration of the goiter area had Tcpo2 levels lower than the controls and patients with venous insufficiency but no skin changes. The more serious the skin changes in patients with venous insufficiency, the lower the fibrinolysis activity. We conclude that extravascular deposition of fibrins in patients with venous disease which block the diffusion and exchanges of oxygen between the blood and tissue is an important factor in the development of venous ulcerations. The decrease of fibrinolysis activity led to the decrease of removing pericapillary fibrins deposition, combined with extravascular fibrin caused venous ulceration.
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PMID:[Pathogenesis of skin pathologic changes and ulceration]. 825 6

Nineteen patients with symptoms of chronic venous insufficiency (CVI) were treated with 13-week cycles of intermittent pneumatic compression (IPC) during 2 h sessions twice weekly, with most treatments at home. At study completion, quantitative subjective scores for total symptomatology were improved in 16/19 patients (84%). Enhancement of fibrinolytic potential in vivo was detected in 86% of observations on specimens from CVI patients over 2 h of IPC, with accelerated euglobulin clot lysis times (ELT) noted within 15 min of initiating compression. The enhanced fibrinolytic potential was attributed to increased urokinase plasminogen activator (u-PA), probably released from perturbed endothelial cells by IPC. Significant decreases in total t-PA antigen (mass concentration) but not t-PA activity, were produced by IPC in CVI patients only (P = 0.0001), with greater effects noted in the non-anticoagulated versus the anticoagulated cohort. Plasminogen activator inhibitor type 1 (PAI-1) levels rose rapidly after IPC only in the controls and non-anticoagulated CVI patients. PAI-1 decreased in those receiving anticoagulation. No platelet perturbation was detected during IPC by measuring levels of beta-thromboglobulin or the thromboxane A2 metabolite, 11-dehydrothromboxane B2; however, significant (P < 0.003) decreases in plasma prostacyclin (PGI2) levels (measured as the stable 6-ketoprostaglandin F-1-alpha-metabolite) were observed after 15 min of IPC in non-anticoagulated CVI patients only. There was no evidence of increased thrombin generation by IPC, determined by urinary excretion of fibrinopeptide A and prothrombin fragment 1. Concurrent anticoagulation appears to mediate more favorable biochemical alterations in CVI, although subjective improvement did not correlate with anticoagulation. The mechanism(s) by which these physiologic changes compliment the mechanical effects of IPC remain to be elucidated and will require adequately controlled and powered studies.
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PMID:Intermittent pneumatic compression in chronic venous insufficiency favorably affects fibrinolytic potential and platelet activation. 883 95

Four cases of proximal deep venous thrombosis treated with streptokinase and tissue plasminogen activator are reported. Therapy monitorization was performed by ultrasonography with color Doppler and thrombolytic agents were used by venous infusion. There was complete lysis in two cases, and the mean rate of venous recanalization was 88%. Reversible hemorrhagic complications were observed in two patients, and late ultrasonographic control (after six months) demonstrated venous insufficiency in one case.
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PMID:[Thrombolytic therapy in deep venous thrombosis. Initial clinical experience]. 943 40

Streptokinase, urokinase, tissue plasminogen activator and similar drugs can all cause lysis of venous thrombi and pulmonary emboli, but there is small evidence that accelerated lysis achieves a significantly better clinical outcome, on average, in the shorter or longer term, than heparin alone. Thrombolytic therapy for deep leg vein thrombosis aims to restore flow and to preserve venous valves, and so to prevent chronic post-phlebitic disability, but no trial has convincingly demonstrated that the last can be achieved in more than a few patients. Only a small minority of people with extensive proximal thrombosis develop disabling post-phlebitic venous insufficiency, and there are no good clinical predictors of this outcome. As a result, any widespread use of thrombolytics would bring an immediate risk of major bleeding to many people who will never be destined to develop a clinically important problem. Thrombolytic therapy after venous thrombosis should be avoided except, perhaps, in a few carefully selected patients with severe obstruction. The case for using thrombolytics after recent pulmonary embolism is strongest in the limited number of patients with ongoing hypoxia, respiratory distress, pulmonary hypertension and right heart failure, because thrombolytic therapy often achieves an impressive and almost immediate clinical benefit in this clinical setting. Whether early relief from pulmonary artery obstruction translates into longer-term advantage over heparin remains uncertain, however, because no comparative trial has ever shown these drugs to reduce mortality after pulmonary embolism. In all cases, both the physician and the patient must balance the certainty of an immediate bleeding risk against the uncertainty of a better than marginal real benefit.
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PMID:Thrombolytic therapy for venous thrombosis and pulmonary embolism. 1033 Oct 98

Despite much research, the aetiology of venous disease is still poorly understood. Since haemostatic factors are involved in the processes of fibrinolysis and platelet aggregation, it is conceivable that such processes may be implicated in the pathology of varicose veins and chronic venous insufficiency (CVI). The Edinburgh Vein Study examined 1566 men and women aged 18-64 years that were randomly selected from the lists of 12 general practitioners. Each subject completed a questionnaire, underwent a comprehensive clinical examination and had a blood sample taken for the analysis of plasma fibrinogen, tissue plasminogen activator (t-PA) and von Willebrand factor (vWF) antigens. Subjects with trunk varicose veins and those with CVI had higher levels of each haemostatic factor compared with those with no trunk varices and no CVI. Although unit increases in t-PA and vWF were initially associated with a significantly increased risk of CVI in men, and both factors with an elevated risk of trunk varices in women, multiple adjustment for age, smoking status and body mass index reduced the odds ratios to non-significance. However, this does not entirely rule out the possibility of a pathogenic role for haemostatic factors in venous disease, but rather indicates the need for further experimental and epidemiological studies.
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PMID:Haemostatic factors and risk of varicose veins and chronic venous insufficiency: Edinburgh Vein Study. 1113 57