In most clinical studies, rt-PA was administered by continuous infusion over a period of 90 min to 8 h. The rationale for such a prolonged rt-PA infusion was based on the fear of a high incidence of rethrombosis due to (1) the moderate hemostatic impairment induced by rt-PA; (2) the short half-life of t-PA; and (3) the general conviction that the affinity for fibrin and the ability of t-PA to be activated by fibrin would be sufficient to provide selective thrombolysis. However, currently adopted regimens of rt-PA administration induce a plasma fibrinolytic state, and although they produce less fibrinogenolysis than streptokinase for an equivalent thrombolytic effect, they are associated with excessive bleeding. Furthermore, there is no clear evidence that rt-PA, with the adopted regimens, has a higher clinical efficacy than streptokinase or urokinase.
Experimental observations and clinical data suggest that different strategies in administering rt-PA could increase both efficacy and safety. Among these strategies is the bolus administration of rt-PA. Biochemical and biologic properties of rt-PA let us foresee potential advantages of this agent, when given as a bolus, over other plasminogen activators. For these reasons, most of this review, dealing with bolus administration of thrombolytic agents, will be dedicated to this agent.