Indeed, the bleeding time, an index of in vivo platelet function, is prolonged in patients receiving streptokinase or rt-PA, and this prolongation is positively correlated with the hemorrhagic risk.
It has been observed, both in vitro41 and in vivo, that plasminogen activators exert a biphasic effect on platelet function. An initial activation step is followed, at longer exposure times, by depression of platelet reactivity due to several mechanisms. These include the cleavage of glycoprotein lb (the platelet receptor for von Willebrand factor), the depletion of the granule storage pool, and the generation of FDPs, which could interfere with the platelet-fibrinogen reaction. Thus, by shortening the time that rt-PA remains in the bloodstream, the period of platelet exposure to plasmin is reduced and, therefore, the impairment of platelet function may be prevented or minimized. Unfortunately, no clinical data are available on the effect of different regimens of rt-PA on platelet function.
Theoretically, the only way to completely prevent bleeding during thrombolysis would be to identify a totally thrombus-specific plasminogen activator, able to discriminate between the fibrin of a thrombus and that of a hemostatic plug.