The Maintenance of a Sustained Thrombolytic State in Man. I. Induction and Effects*

coccal metabolism, is a highly effective activator of human plasminogen. Plasmin, the enzyme formed following plasminogen activation, exerts powerful proteolytic and fibrinolytic effects at neutral hydrogen ion concentrations, which in vivo mediate the mechanisms of physiological fibrinolysis. Consequently, hopes have been entertained that the intravenous injection of streptokinase, or of streptokinase-activated plasmin, might prove to be of benefit in the therapy of human thromboembolic disease. Animal experiment, despite the lessened effectiveness of streptokinase as an activator of animal plasminogen and the difficulties of species variability, has yielded striking findings. The intravenous injection of very large doses of streptokinase has been shown to produce lysis of artificially produced thrombi in the arteries of dogs (1) and in the veins of rabbits (2), to cause the clearance of peritoneal exudate evoked by trauma (3) and more recently to prevent or remove fibrinoid lesions secondary to the generalized Shwartzman response (4). These findings appear to be of unequivocal significance but the precise mechanism of their production has been uncertain.