The relevance of this phenomenon could be even more striking when rt-PA is administered in the presence of the large fibrin-rich thrombi encountered in DVT and pulmonary embolism, which are likely to release large amounts of cross-linked FDPs. This may explain the high incidence of bleeding when t-PA is used in treatment of DVT. Limiting t-PA-associated bleeding, therefore, may require measures aimed at decreasing fibrinogenolysis. It is not possible to eliminate cross-linked FDPs from the circulation, since they are the result of effective thrombolysis. A rapid infusion of rt-PA, due to its short half-life, makes available only small amounts of circulating rt-PA for interaction with FDPs, thereby limiting their potential for promotion of fibrinogenolysis. This hypothesis is supported by studies in experimental animals, in which a rapid rt-PA infusion was associated with less fibrinogenolysis and bleeding than prolonged infusion regimens.
The effects of the activation of the fibrinolytic system on platelet behavior are complex. Both enhancement and inhibition of platelet reactivity have been described after in vitro or in vivo exposure of platelets to plasminogen activators.- While activation of platelets is thought to be involved in the pathogenesis of rethrombosis, a platelet defect occurring during or immediately after thrombolytic treatment could contribute to the bleeding.