Experiences with pro-urokinase and potentiation of its fibrinolytic effect by urokinase and by tissue plasminogen activator.
Pro-urokinase is a single chain, precursor form of two chain, 54,000 Mr urokinase. Although originally isolated from urine, pro-urokinase is also found in blood, where it is believed to participate in natural fibrinolysis alongside tissue plasminogen activator (t-PA). These two plasminogen activators share the property of inducing fibrin-selective plasminogen activation, but many of their other properties, including their modes of action, are dissimilar. A comparison of some of the clinically relevant properties of pro-urokinase and t-PA is provided. A multicenter, dose-finding clinical trial of native pro-urokinase is underway in the United States and in West Germany. At the time of this writing, 110 patients with angiographically proved acute coronary thrombosis have been treated. The findings from one center are summarized in some detail and the overall experience is reviewed. Preliminary evidence for a potentiating effect on pro-urokinase-induced thrombolysis by urokinase is presented. The findings suggest that a bolus of urokinase (200,000 IU) at the outset increases the reperfusion rate from 60 to greater than 80% and shortens the lysis time from about 50 to 30 minutes. A modest (19%) but significant (p less than 0.05) decrease in fibrinogen accompanied thrombolysis by urokinase/pro-urokinase. Nonetheless, significant bleeding complications in the multicenter study have, to date, not been encountered and it is suggested that this may be related to pro-urokinase's sensitivity to inactivation by thrombin and lack of potentiation by heparin.(ABSTRACT TRUNCATED AT 250 WORDS)
D000208:Acute Disease; D002986:Clinical Trials as Topic; D003328:Coronary Thrombosis / Q000188:drug therapy; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D010960:Plasminogen Activators / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator