Even more than the improved efficacy, the major potential advantage of a bolus administration of rt-PA seems to be the reduced risk of hemorrhagic complications. A decrease in the frequency or severity of bleeding, particularly intracranial bleeding, could indeed favor a greater utilization of thrombolytic treatment, particularly in clinical disorders with low mortality, such as deep vein thrombosis (DVT).
Several mechanisms have been suggested as being responsible for the bleeding complications seen during or after thrombolysis: (a) the coagulation defect, secondary to the uncontrolled action of plasmin on coagulation factors; (b) the induction of a platelet function defect; and (c) the lysis of a hemostatic plug.
The link between systemic plasminemia and bleeding emerged from the results of clinical studies showing a correlation between the bleeding side effects and both the levels of FDPs and the degree of hypofibrinogenemia. Bleeding events occurred 2.12 times as often in patients with serum FDP levels higher than 85 |ig/ml as in patients with serum levels lower than 22 jig/ml.
Weitz et al investigated the mechanism by which a clot-specific agent like rt-PA produces fibrinogeno-lysis. Plasma was incubated with increasing concentrations of rt-PA in the presence or absence of a fibrin clot.