Elfects of Aspirin and Prostaglandin E1 on In Vitro Thrombolysis With Urokinase Evidence for a Possible Role of Inhibiting Platelet Activity in Thrombolysis

The formation of thrombi in vivo includes the activation of both platelets and the coagulation cascade. Conventional thrombolytic therapy is primarily directed toward the dissolution of fibrin. To evaluate the possibility that platelet activity impairs the lysis of thrombi, we studied the effects of aspirin and platelet-deaggregating prostaglandin El on thrombolysis with urokinase. Combined platelet and fibrin thrombi were produced in vitro by adding CaCI2 and collagen (1 ,ug/ml) to citrated platelet-rich plasma (250,000 platelets per ,ul). Urokinase (50010,000 units/ml) caused a dose-dependent weight loss of the thrombi that was maximal at 2,000 units/ml. The addition of aspirin (10-200 ,ug/ml) to platelet-rich plasma before thrombus formation markedly enhanced thrombolysis with urokinase. This effect was most pronounced at 20 ,ug/ml aspirin. However, when aspirin was added after completion of thrombus formation,