Safety and efficacy of tissue-type plasminogen activator produced by recombinant DNA technology.

Because of its enhanced activation of plasminogen in association with fibrin compared with free plasminogen, tissue-type plasminogen activator (t-PA) evoked excitement as a potentially useful pharmacologic activator of the fibrinolytic system. Initial studies in experimental animals and patients demonstrated that it induced coronary thrombolysis rapidly and without concomitant, marked fibrinogenolysis in contrast to streptokinase. Large scale clinical trials soon followed. Their results indicate that intravenous administration of t-PA produced by recombinant DNA technology (rt-PA) elicits coronary thrombolysis in two-thirds or more of treated patients with angiographically documented thrombotic occlusions generally without perturbing hemostatic mechanisms or inducing marked fibrinogenolysis. Bleeding is usually confined to vascular access sites and episodes of major bleeding are rare. Overall 6 week survival for treated patients with documented acute myocardial infarction may be as high as 95%.