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Fibrin-specific thrombolysis with tissue-type plasminogen activator (t-PA) and single chain urokinase-type plasminogen activator
SYMPOSIUM X:
THROMBOLYSIS: CLINICAL AND BIOCHEMICAL ASPECTS THURSDAY, June 5, 1986 Abstract No. 250 - Abstract No. 253
250 FIBRIN-SPECIFIC THROMBOLYSIS WITH TISSUE-TYPE PLASMINOGEN ACTIVATOR (t-PA) AND SINGLE CHAIN UROKINASE-TYPE PLASMINOGEN ACTIVATOR. Desire Collen, Center for Thrombosis and Vascular Research, University of Leuven, Leuven. Two physiological plasminogen activators, tissue-type plasminogen activator (t-PA) and single chain urokinase-type plasminogen activator (scu-PA), induce clot-specific thrombolysis, however via entirely different mechanisms. 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 three multicenter clinical trials in patients with acute myocardial infarction, intravenous infusion of 0.5 mg to 1 mg of t-PA per kg body weight over 1 to 3 hrs resulted in coronary reperfusion in approximately 70 percent of patients, but was associated with an average decrease of the plasma fibrinogen level by 30 percent. Clot-specific thrombolysis by natural or recombinant scu-PA has also been demonstrated in animal models of pulmonary embolism, venous thrombosis and coronary artery thrombosis. We have treated six patients with acute myocardial infarction with scu-PA and obtained coronary reperfusion during intravenous infusion of 40 mg scu-PA over 60 min in four of the patients and during subsequent intracoronary infusion in one additional patient. A decrease of fibrinogen to 25 percent of the preinfusion value was however observed in one patient. 251 PHARMACOLOGICAL ASPECTS AND LABORATORY CONTROL OF THROMBOLYTIC AGENTS. Laboratoire Central d'Hematologie - H8tel-Dieu - Paris (France) M.SAMAMAThe modifications induced by thrombolytic treatments with streptokinase (SK) or urokinase (UK) are now well documented and, according to the NIH consensus (19801, the laboratory monitoring could be restricted to thrombin time. However, this attitude is disputed. Fibrinogen determination may have some interest, in UK treatments for instance, since it has been shown that hypofibrinogenemia could be related to the clinical results and since UK has a dose-dependent effect..However, various methods used for fibrinogen determination may give different results. Heparin is sometimes associated with thrombolytic therapy, requiring heparin monitoring ; then, the combination of reptilase and thrombin clotting time may help to differentiate anticoagulant activity of heparin and FDP. New drugs, such as acyl-enzymes, t-PA and pro-UK, are now being used. Thrombolytic and fibrinogenolytic properties of these different drugs at various concentrations have been studied in vitro after addition to plasma and on standard hanging clots. Modifications induced in treated natients are presently under evaluation. Newly developed tests (t-PA and t-PA inhibitor D-dimer, etc...) may help in the choice of the treatment regimen and uossibly, to predict efficacy of the treatment.
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THROMBOLYSIS: CLINICAL AND BIOCHEMICAL ASPECTS THURSDAY, June 5, 1986 Abstract No. 250 - Abstract No. 253
250 FIBRIN-SPECIFIC THROMBOLYSIS WITH TISSUE-TYPE PLASMINOGEN ACTIVATOR (t-PA) AND SINGLE CHAIN UROKINASE-TYPE PLASMINOGEN ACTIVATOR. Desire Collen, Center for Thrombosis and Vascular Research, University of Leuven, Leuven. Two physiological plasminogen activators, tissue-type plasminogen activator (t-PA) and single chain urokinase-type plasminogen activator (scu-PA), induce clot-specific thrombolysis, however via entirely different mechanisms. 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 three multicenter clinical trials in patients with acute myocardial infarction, intravenous infusion of 0.5 mg to 1 mg of t-PA per kg body weight over 1 to 3 hrs resulted in coronary reperfusion in approximately 70 percent of patients, but was associated with an average decrease of the plasma fibrinogen level by 30 percent. Clot-specific thrombolysis by natural or recombinant scu-PA has also been demonstrated in animal models of pulmonary embolism, venous thrombosis and coronary artery thrombosis. We have treated six patients with acute myocardial infarction with scu-PA and obtained coronary reperfusion during intravenous infusion of 40 mg scu-PA over 60 min in four of the patients and during subsequent intracoronary infusion in one additional patient. A decrease of fibrinogen to 25 percent of the preinfusion value was however observed in one patient. 251 PHARMACOLOGICAL ASPECTS AND LABORATORY CONTROL OF THROMBOLYTIC AGENTS. Laboratoire Central d'Hematologie - H8tel-Dieu - Paris (France) M.SAMAMAThe modifications induced by thrombolytic treatments with streptokinase (SK) or urokinase (UK) are now well documented and, according to the NIH consensus (19801, the laboratory monitoring could be restricted to thrombin time. However, this attitude is disputed. Fibrinogen determination may have some interest, in UK treatments for instance, since it has been shown that hypofibrinogenemia could be related to the clinical results and since UK has a dose-dependent effect..However, various methods used for fibrinogen determination may give different results. Heparin is sometimes associated with thrombolytic therapy, requiring heparin monitoring ; then, the combination of reptilase and thrombin clotting time may help to differentiate anticoagulant activity of heparin and FDP. New drugs, such as acyl-enzymes, t-PA and pro-UK, are now being used. Thrombolytic and fibrinogenolytic properties of these different drugs at various concentrations have been studied in vitro after addition to plasma and on standard hanging clots. Modifications induced in treated natients are presently under evaluation. Newly developed tests (t-PA and t-PA inhibitor D-dimer, etc...) may help in the choice of the treatment regimen and uossibly, to predict efficacy of the treatment.
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