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)

Thrombotic processes play a role not only as a sequel of arteriosclerosis, but also for its pathogenesis. Under this aspect a pharmacological regulation of the course of the reaction of thrombpcytes, the blood coagulation and the fibrinolysis gets significance. The prevention of the formation of fibrin by well-known anticoagulants, such as coumarines and heparin, seems little suited for a prophylaxis of arteriosclerosis. By a pharmacological regulation of the reaction of the blood platelets which are decisive for the initial phase of the formation of thrombi new possibilities for an intervention into the pathomechanisms of arteriosclerosis are the result. Her also realizations concerning the prostaglandin metabolism of the blood platelets and of the wall of vessels can be evaluated. The activation of fibrinolysis by means of the hitherto introduced fibrinolytics, such as streptokinase and urokinase, is used above all for the treatment of acute thrombi. In the sense of a prevention of arteriosclerosis the activation of the endogenic fibrinolysis with the help of indirect fibrinolytics, which effect a liberation of the activators of fibrinolysis localised in the wall of the vessels, is a hopful way.
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PMID:[Possibilities of prevention and therapy of arteriosclerosis by influencing hemostatic functions]. 70 99

Alteplase and saruplase are more fibrin-specific thrombolytic drugs than anistreplase. These and the thrombolytic drugs of the first generation (streptokinase and urokinase) have shortcomings and limitations. The prolonged intravenous maintenance infusions have been replaced by a bolus injection, accelerated infusions, or the combined intravenous administration of thrombolytic agents. Numerous truncated alteplase or saruplase molecules have been constructed by deletion and domain substitution or hybrids made of the two molecules without gaining in thrombolytic potency. Recombinant staphylokinase and plasminogen activator from bat saliva have some interesting properties and are being investigated. Thrombus-targeted thrombolytic drugs were constructed using monoclonal antibodies against fibrin fragments or against epitopes of activated platelets. Fibrin-specific thrombolytic drugs require the concomitant use of a potent antithrombotic drug to prevent reocclusion. Whether hirudin or synthetic thrombin inhibitors are superior to heparin and whether novel antiplatelet agents, including monoclonal antibodies to platelet receptors and disintegrins, are more effective than aspirin is under clinical investigation. The place of stable analogues of prostacyclin during thrombolytic treatment is still unsettled.
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PMID:Advances in thrombolytic therapy. 139 Mar 21

Heparin-induced thrombocytopenia with thrombotic complications is a serious clinical problem. The diagnosis is confirmed by a positive heparin-induced platelet aggregation test and/or detection of white clots upon pathological exam after a presumptive diagnosis based on these criteria: (1) Development of thrombocytopenia of less than 100,000 mm3 while receiving heparin therapy; (2) Normalization of the platelet count after an interruption in heparin therapy; (3) The presence of thrombotic complications; and (4) Exclusion of other causes of thrombocytopenia. Eight patients with heparin-induced thrombocytopenia were encountered at the Charleston Area Medical Center, Memorial Division, in a recent 20-month period. Various types of heparin, routes of administration, and indications were implicated. The mean platelet nadir was 25,750 mm3 and the mean time to onset of of heparin-induced thrombocytopenia was 4.9 days. Thrombotic complications included seven patients with arterial occlusions of the legs, six with deep-vein thrombosis of the legs (three had pulmonary embolism), and five with combined arterial and venous thrombosis. Treatment strategies included discontinuation of heparin in all patients; intravenous infusion of dextran in five patients, followed by arterial thrombectomy in three patients; urokinase therapy in two patients for arterial thrombotic complications; and insertion of Greenfield filters in four patients for venous thrombotic complications. All surviving patients were given warfarin. The mortality rate was 25 percent and the morbidity rate was 38 percent. In conclusion, an initial platelet count should be obtained on all patients prior to receiving heparin, followed by repeat platelet counts every two to three days. Once thrombocytopenia or thrombosis is diagnosed, heparin should be discontinued and other therapeutic modalities considered.
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PMID:Heparin-induced thrombocytopenia with thrombotic complications. 157 77

A retrospective analysis of our experience with intraprocedural thrombus complicating percutaneous transluminal coronary angioplasty (PTCA) was undertaken. Of 983 PTCA procedures reviewed, 62 (6.3%) were complicated by thrombus. Patients were managed conservatively (group I, n = 18), with redilation (group II, n = 17), or with intracoronary urokinase and redilation (group III, n = 27). The three groups did not differ with respect to demographic or baseline angiographic variables, but complications, defined as death, myocardial infarction, bypass surgery, or threatened occlusion requiring emergency stenting, occurred in 11% of patients in group I, 24% in group II, and 48% in group III. Occlusive thrombus behavior was observed in 80% of these 62 patients. Patients with complications were less likely to have received antecedent antiplatelet therapy (79% vs 95% of patients without complications), had more complex baseline lesion morphology, more often had thrombus present at baseline (42% vs 19%), and more often had a low activated clotting time at the start of PTCA (53% vs 8%). Thrombi that led to complications more frequently exhibited occlusive behavior before therapy was begun (95% vs 71%) and more often occurred in the setting of intimal dissection (42% vs 14%). Patients undergoing PTCA at the time of diagnostic catheterization were more likely to have complications than those in whom PTCA was delayed. A successful outcome was more likely (83% vs 27%, p = 0.03) in group III if at least 140,000 U of urokinase were administered within 50 minutes of the appearance of thrombus. Thus intracoronary thrombus formation during PTCA remains a significant source of morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Management and immediate outcome of patients with intracoronary thrombus during percutaneous transluminal coronary angioplasty. 161 90

The effect of ultrasound energy on fibrinolysis of artificial thrombus in vitro was investigated. Thrombi produced by the Chandler loop method were exposed to low-energy ultrasound (5,000-6,000 Pa) in an ultrasound bath (48 kHz) for 60 seconds. Fibrinolysis with urokinase was enhanced from 40.6% +/- 1.8% to 59.2% +/- 2.6% (mean +/- standard deviation) with ultrasound exposure after a 60-minute incubation. Ultrasound alone without urokinase resulted in no fibrinolysis. In a second experiment, a newly developed miniature ultrasound-emitting ceramic element (2 x 1 x 5 mm) was attached to the tip of a catheter. Ultrasound exposure (225 kHz) from this device markedly enhanced fibrinolysis with urokinase from 8.9% +/- 1.5% to 37.3% +/- 0.8% (total ultrasound exposure 60 seconds, intensity 30 mW/cm2) after a 30-minute incubation. After a 120-minute incubation, fibrinolysis with ultrasound exposure was 61.1% +/- 1.8% versus 46.7% +/- 0.5% for the unexposed group. Ultrasound enhancement of fibrinolysis was less pronounced with longer incubation time (60 or 120 minutes). Ultrasound energy enhanced fibrinolysis with urokinase, especially in the early phase of lysis. This new device may shorten the time needed to complete fibrinolysis and reduce total drug dosage needed for treatment of thromboembolic diseases.
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PMID:Enhancement of fibrinolysis with ultrasound energy. 162 77

This study describes our experience with 12 patients with white clot syndrome encountered during a recent 36-month period. The diagnosis was based on the following criteria: (1) development of thrombocytopenia of less than 100,000/mm3 during administration of heparin therapy, (2) normalization of the platelet count after an interruption in heparin therapy, (3) exclusion of other causes of thrombocytopenia, (4) a positive heparin-induced platelet aggregation test, (5) detection of white clots on pathologic examination, and (6) the presence of thrombotic complications. Of 2,500 patients who received heparin therapy, 12 (0.48%) developed white clot syndrome. Various indications, routes of administration, and types of heparin were implicated. The mean platelet nadir was 26,900/mm3, and the mean time to onset of heparin-induced thrombocytopenia was 5 days. Thrombotic complications included arterial occlusions of the legs in 11 patients, deep vein thrombosis of the legs in 9 patients (4 had pulmonary embolism), and combined arterial and venous thrombosis in 8 patients. Treatment strategies included discontinuation of heparin in all patients and intravenous infusion of dextran, followed by arterial thrombectomy in four patients, urokinase therapy in two patients for arterial complications, and insertion of Greenfield filters in six patients. All patients were given warfarin. The mortality rate was 25% and the morbidity rate was 50%. An initial platelet count should be obtained on all patients prior to receiving heparin, followed by repeat platelet counts every 2 to 3 days. Once thrombocytopenia or thrombosis is diagnosed, heparin should be discontinued and other methods of therapy considered.
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PMID:Diagnostic and therapeutic strategies of white clot syndrome. 171 45

The thrombolytic and systemic effects of BM 06.022 were evaluated and compared with those of alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis. BM 06.022 consists of the kringle-2 and protease domains of human tissue plasminogen activator (t-PA) and is unglycosylated because of its expression in Escherichia coli cells. Thrombus formation in anesthetized open chest dogs was induced by electrical injury to the intimal surface of the left circumflex coronary artery at a high level site of obstruction. In heparinized dogs, none of six vehicle-treated animals exhibited reperfusion. Reperfusion was achieved in four of six dogs at 18.3 +/- 6 min after intravenous bolus injection of 140 kU/kg (0.24 mg/kg) of BM 06.022, whereas four of six dogs exhibited reperfusion later (p less than 0.05) at 76.5 +/- 16.1 min during infusion of 1.33 mg/kg of alteplase (0.13 mg/kg as initial bolus injection, followed by 0.66 mg/kg over 1 h and 0.53 mg/kg over 2 h). Significantly later (p less than 0.05) reperfusion than that achieved with BM 06.022 was achieved in five of six dogs at 57.8 +/- 12.1 min after intravenous injection of 0.4 U/kg of anistreplase. Streptokinase (21,000 IU/kg over 60 min) and urokinase (20,000 IU/kg as an intravenous bolus injection, followed by 20,000 IU/kg over 89 min) each induced reperfusion in three of six dogs but at 67 +/- 12 and 84.3 +/- 17.1 min (p less than 0.05 vs. BM 06.022), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of thrombolytic and systemic effects of the novel recombinant plasminogen activator BM 06.022 compared with alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis. 173 72

Thrombotic occlusion of the superior vena cava is an uncommon but serious complication of chronic indwelling venous catheters. Several reports have shown thrombolytic therapy with intravenous streptokinase or urokinase to be effective in the treatment of this condition. We report a case of superior vena cava thrombosis in a 53-year-old woman receiving chemotherapy for breast carcinoma through a subcutaneously implanted venous access catheter who was successfully treated with peripheral infusion of recombinant tissue type plasminogen activator (rtPA).
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PMID:Treatment of superior vena cava thrombosis with recombinant tissue type plasminogen activator. 190 61

Thrombus immunoscintigraphy with radiolabeled monoclonal antibodies are presently undergoing intense clinical evaluations. Reports on clinical trials of radiolabeled antifibrins are very encouraging and results of antiplatelet antibody evaluations are forthcoming. Animal studies with antiplatelet antibodies indicate that a diagnosis can be made within the critical "lytic window" of 4-6 h, and thus the imaging procedure may be used as an adjunct to thrombolytic therapy, i.e. screening of patients. We now report on a potentially new application of monoclonal antibodies, immunoimaging for monitoring thrombolysis. In vitro studies were performed with "standardized clots" incubated with 99mTc 50H.19 and re-incubated with streptokinase (SK), urokinase (UK) or recombinant tissue plasminogen activator (rt-PA). The decrease in clot-bound 99mTc 50H.19 activity after SK, UK or rt-PA incubation was proportional to the decrease in clot weight (r = 0.90-0.98). The direct effects of these thrombolytic agents on the labeled antibody and the possible interference of aspirin, warfarin and heparin in thrombus immunoimaging were also investigated. Aspirin, heparin and warfarin did not interfere with clot-binding of 99mTc 50H.19. Thrombolytic agents did not affect the stability of the radiolabel or immunoreactivity of 50H.19. These results indicate that 99mTc 50H.19 is a promising agent that may enable monitoring thrombolysis in addition to thrombus immunoimaging.
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PMID:A monoclonal antibody reacting with platelets for monitoring thrombolysis. 190 49

Thrombotic events are a serious and potentially fatal complication during the neonatal period. Despite clinically serious thromboses in up to one percent of neonates and less severe complications (e.g., catheter malfunction secondary to clots) in a much higher percentage, well-designed studies on prevention and treatment of thromboses are lacking. Treatment approaches are largely anecdotal and involve the use of heparin and, occasionally, thrombolytics. Proper monitoring of anticoagulant and thrombolytic effects is difficult because of the limited blood volumes available from neonates and the relatively large sample volumes needed for most coagulation studies. Activated clotting times (ACTs) are preferred because they use low blood volume and are a rapid bedside test. Heparin should be administered with an initial loading dose of 50-100 units/kg followed by a continuous infusion of 20 units/kg/h. Further doses should then be adjusted based on the ACT, targeting a value of 1.5-2.5 times the control. Thrombolytics also have been used in several case reports and are guided by both clinical response and serial D-dimer values. We prefer urokinase 100 units/kg/h for local infusion to the thrombus and urokinase 1000-10,000 units/kg/h for systemic therapy.
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PMID:Neonatal thrombosis: treatment with heparin and thrombolytics. 194 44


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