Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of streptokinase and urokinase to lyse intravascular fibrin-based clots is firmly established. However, there is a lack of enthusiasm for these agents because of serious haemorrhagic complications and a lack of controlled randomized studies indicating their efficacy. Thrombolytic therapy is suitable in only 15 per cent of patients with acute deep venous thrombosis. It restores the venous circulation to normal in up to 95 per cent of these patients if therapy is instituted within 5 days of the onset of symptoms. These patients have significantly fewer symptoms on follow-up than patients treated with heparin although the ability of thrombolytic therapy to preserve venous valvular function and to prevent the post-phlebitic syndrome is now in question. Thrombolytic therapy is as effective as heparin in preventing pulmonary embolism and may be superior in its treatment. Pulmonary haemodynamics are rapidly improved, diffusion capacity is restored and, although the evidence is inconclusive, long-term pulmonary hypertension may be prevented. Although the mortality rate is not decreased, controlled studies show that thrombolytic therapy may be beneficial in massive pulmonary embolism with clinical shock. Thrombolytic therapy is indicated for acute arterial and acute bypass graft occlusion when the surgical alternative is associated with a higher morbidity and mortality. Partial thrombolysis is achieved in up to 90 per cent of cases and the need for further therapeutic intervention is eliminated in one-third of the patients treated. New thrombolytic agents with greater specificity and potentially greater efficacy and fewer complications are being developed. Tissue plasminogen activator has been successfully used. Prourokinase, fibrin-seeking urokinase and acetylated streptokinase-plasminogen complex may expand the role of thrombolytic therapy in surgical practice.
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PMID:The role of thrombolytic therapy in surgical practice. 265 13

We report the clinical, echocardiographic and therapeutic aspects and the evolution of 7 cases of right cardiac migrant thromboembolus in pulmonary embolism (5 M and 2 F, aged 43 to 91). Our data are also compared with all the cases reported in the literature (77 patients). During a sample year (1987) we systematically performed two-dimensional echocardiograms (2D Echo) as early as possible in all the patients admitted to our Coronary Care Unit for suspected pulmonary embolism; among 42 patients the diagnosis of pulmonary embolism was confirmed in 30 out of 42 patients. A relatively high incidence of thromboembolus was found (5/30, 17% in 1987); this finding seems to be relative to the early execution of the 2D Echo study (thromboembolus was found in 4/5 patients when 2D Echo was performed within 20 hours and in only 1/23 when 2D Echo was performed later). The 2D Echo was always evocative of freely floating migrant thromboembolus (6 in right atrium, 1 in right ventricle) and no differential diagnosis with thrombi in situ or other masses was necessary. The therapy for 6 patients hospitalized for pulmonary embolism and surviving the first hours (1 patient died immediately) was: surgical in 1 case, medical in the other 5. Medical therapy consisted only of heparin-calcium in one patient and heparin-calcium + dipyridamole in another because of contra-indications for more aggressive therapy. One patient underwent anticoagulant therapy with i.v. heparin. The remaining two underwent fibrinolytic therapy with urokinase and, afterwards, anticoagulant therapy: in 1 case the therapy was started after the embolization of the mass in the pulmonary artery had occurred; in the other one we observed the progressive reduction of thromboembolus until its disappearance within 5 days without any signs of further embolization. All patients survived and were discharged within 25 days, despite the occurrence of lung embolization in 4 of them. The review of 77 cases reported in the literature shows good outcomes for embolectomy when compared with medical therapy, but almost half of the patients underwent surgical therapy directly. Medical therapy experience, particularly with thrombolytic agents (10 cases in all), is still too scarce to exclude its role, as indeed our experience seems to indicate.
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PMID:[Thromboembolus migrating into the right heart in pulmonary embolism. Echocardiographic and clinico-therapeutic aspects in 7 cases and review of the literature]. 266 84

Clinical experience with thrombolytics in non-coronary disorders is limited to the plasminogen activators streptokinase, urokinase and alteplase; therapeutic trials with anistreplase (APSAC) are almost, and with saruplase completely, limited to acute myocardial infarction. In terms of thrombus clearance, thrombolytic drugs are superior to heparin in patients with recent deep vein thrombosis in the pelvis or lower limbs. In aggregate, thrombi younger than 8 days are lysed in approximately 60% of patients treated with streptokinase, urokinase or alteplase. The results of studies assessing the subsequent development of the postphlebitic syndrome are conflicting, but most suggest that thrombolytic therapy can reduce symptoms of chronic venous insufficiency. Currently, the combination of systemic thrombolytic drugs followed by heparin is recommended for patients with acute major pulmonary embolism who are haemodynamically unstable. Streptokinase, urokinase and alteplase have all been shown to accelerate the lysis of pulmonary emboli and to decrease pulmonary vascular obstruction and pulmonary hypertension. Systemic venous or intrapulmonary infusions of alteplase offers the same benefit in terms of angiographic and haemodynamic improvement. A short infusion of 100 mg alteplase over 2 hours seems to be superior to a 24-hour infusion of urokinase. None of the thrombolytic trials in pulmonary embolism have been large enough to demonstrate a reduction in mortality. It is now generally accepted that, unless contraindicated, thrombolytic therapy is the front-line treatment for patients with massive pulmonary embolism and major haemodynamic disturbance. The local treatment of acute arterial occlusion in limb arteries results in rapid clearing of the artery in 67% of patients treated with streptokinase; the corresponding success rates for urokinase and alteplase are 81% and 88 to 94%, respectively. The main question appears to be the identification of patients in whom local thrombolysis is the treatment of choice, as opposed to established therapeutic modalities. Thrombolytic treatment following a major ischaemic stroke is hazardous, although clinical improvement has been noted in a minority of patients with recanalised cerebral arteries. The safety and efficacy of thrombolytic treatment remains unproven for this indication, and its use must be restricted to experimental protocols. Thrombolytic treatment in retinal artery or vein occlusion has, in practice, been abandoned.
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PMID:Use of thrombolytic drugs in non-coronary disorders. 268 38

Various interventions are available to assist in the management of patients with pulmonary embolism. Most are reserved for patients who either fail standard systemic anticoagulation therapy or are not candidates for anticoagulant therapy. The most common intervention is placement of a vena caval filter. Several different filter devices are available, most of which may be placed percutaneously. Pulmonary thrombolysis with urokinase or streptokinase may be appropriate in some patients with severe, symptomatic pulmonary embolism. Finally, pulmonary embolectomy by means of either a transvenous catheter or surgical technique may be necessary in cases of refractory cardiovascular collapse.
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PMID:Interventions in pulmonary embolism. 269 5

The purpose of this study is the retrospective evaluation of the treatment of 196 cases of pulmonary embolism. Therapeutic attitude was standardized. Intravenous heparin followed early on by oral anticoagulants remains the basic treatment of the majority of patients (74%). This treatment could be associated with: (1) Fibrinolysis with urokinase bolus at the time of massive pulmonary embolism with clinical and hemodynamic signs of shock (14%). No severe hemorrhagic complication was observed. 2) Inferior vena caval interruption in case of contraindications or failure of anticoagulation (29%). Only one death was observed in this study.
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PMID:[Therapeutic approach to pulmonary embolism]. 277 95

We report on two patients, both with massive pulmonary embolism. One was effectively treated with small local doses of urokinase and mechanical fragmentation of the embolus. In the second case, despite previous ineffective systemic lytic therapy with urokinase, the local treatment with streptokinase and embolus fragmentation led to complete lysis of the emboli.
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PMID:[Thrombus fragmentation and local lysis in extensive pulmonary embolisms]. 284 78

The effect of intravenous recombinant human tissue-type plasminogen activator (rt-PA) was compared with that of urokinase in 45 patients with angiographically documented pulmonary embolism (PE) in a randomised controlled trial. The two principal end-points were clot lysis at 2 h, as assessed by angiography, and pulmonary reperfusion at 24 h, as assessed by perfusion lung scanning. All patients received the full dose of rt-PA but urokinase infusions were terminated prematurely (on average after 18 h) in 9 patients because of allergy in 1 and uncontrollable bleeding in 8. By 2 h, 82% of rt-PA-treated patients showed clot lysis, compared with 48% of urokinase-treated patients (p = 0.008; 95% CI for the difference = 10-58%). Improvement in lung scan reperfusion at 24 h was identical in the two treatment groups. The reduction in fibrinogen did not differ significantly between the rt-PA and urokinase groups (45% vs 39% at 2 h and 34% vs 40% at 24 h). The results indicate that in the dose regimens employed, rt-PA acts more rapidly and is safer than urokinase in the treatment of acute PE.
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PMID:Randomised controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism. 289 18

Between October 1982 and July 1984 systemic thrombolysis was carried out in 10 patients (5 males and 5 females aged 19 to 66 years) with massive pulmonary embolism (PE). Mean thrombolytic treatment duration was 77 hours. The main fibrinolytic agent used (9 cases) was streptokinase. Sequential treatment with streptokinase and urokinase was given to 2 patients and urokinase alone to one. 5 patients received porcine plasmin additionally, and one patient BRL 26921 (streptokinase-plasminogen complex) and human plasminogen. Pulmonary arterial pressures were recorded serially. Pulmonary angiograms were obtained before, occasionally during and after thrombolysis. Pulmonary arterial pressures (systolic: p less than 0.01, diastolic: p less than 0.05, mean: p less than 0.01, paired t-test, two tailed) and pulmonary angiograms (p less than 0.001, paired t-test, two tailed) all showed significant improvement. Thrombolytic treatment had to be discontinued in two patients due to side effects. Patients with the most recent PE showed the best response. Patients with recurrent PE and preexisting pulmonary hypertension showed no improvement. In PE without deep vein thrombosis (DVT), treatment duration of up to three days seems to be appropriate. In PE with concomitant DVT the treatment should be prolonged to achieve complete lysis of thrombi.
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PMID:[Fibrinolysis therapy in massive lung embolism. Experiences in 10 patients 1982-1984]. 293

Low molecular weight urokinase (LMW-UK) was coupled to the heavy chain of plasmin to make it able to bind to fibrin. The purified conjugate (PHC-UK conjugate), which consisted of equimolar concentrations of each starting material had a molecular weight of 93,600, bound tightly to fibrin-monomer-Sepharose and was not washed off with 1 M NaCl, but was eluted specifically with epsilon-amino caproic acid. The conjugate showed higher fibrinolytic activity than HMW-UK. A control conjugate prepared by coupling human serum albumin to LMW-UK (HSA-UK conjugate) showed the same fibrinolytic activity as HMW-UK. The half-lives of these two conjugates in rabbits were about 3 times that of HMW-UK. In an experimental pulmonary embolism model in rabbits, the PHC-UK conjugate showed about 10 times higher thrombolytic activity than HMW-UK, while the HSA-UK conjugate showed similar thrombolytic activity as HMW-UK, and moreover caused severe systemic fibrinogen breakdown. Thus the significant increase in thrombolytic activity after injection of PHC-UK conjugate into rabbits may be due to its newly acquired fibrin binding activity, and not to increase in its half-life. It is concluded that the PHC-UK conjugate may be useful in treatment of thrombosis.
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PMID:The plasmin heavy chain-urokinase conjugate: a specific thrombolytic agent. 295 92

The mammalian fibrinolytic system comprises a proenzyme, plasminogen, which can be converted to the active enzyme plasmin, which will degrade fibrin. Plasminogen activation is mediated by plasminogen activators which are classified as either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA). t-PA and single-chain u-PA (scu-PA) induce clot-specific thrombolysis, however via entirely different mechanisms. t-PA is relatively inactive in the absence of fibrin, but fibrin strikingly enhances the activation rate of plasminogen by t-PA. This is explained by an increased activity of fibrin-bound t-PA for plasminogen and not by alteration of the catalytic efficiency of the enzyme. scu-PA has a high affinity for plasminogen but, however, does not activate plasminogen in plasma in the absence of a fibrin clot, due to competitive inhibition. Fibrin-specific thrombolysis appears to be due to the fact that fibrin reverses the competitive inhibition, but this does not seem to occur via specific binding of scu-PA to fibrin. The thrombolytic efficacy and fibrin-specificity of natural and recombinant t-PA has been demonstrated in animal models of pulmonary embolism, venous thrombosis and coronary artery thrombosis. In all these studies thrombolysis and relative fibrinogen sparing effect of t-PA was recently confirmed in several multicenter clinical trials in patients with acute myocardial infarction. Specific thrombolysis by scu-PA has also been demonstrated in animal models of pulmonary embolism, venous thrombosis and coronary artery thrombosis.
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PMID:Fibrin-specific thrombolytic agents. 304 5


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