Interactions between pharmacologic concentrations of plasminogen activators and platelets

Abstract

Because interactions between platelets and plasminogen activators are likely to influence the clinical outcome of coronary thrombolysis, we characterised changes in aggregation of platelets from canine and human whole blood exposed to pharmacologic concentrations of tissue-type plasminogen activator (t-PA) or streptokinase (SK). Aggregation of canine platelets in response to ADP or to collagen decreased markedly after exposure to 5000 ng/ml of t-PA. In contrast, canine platelets exposed to 250 U/ml of SK exhibited little change or slight enhancement of aggregation. After exposure of human platelets to 5000 ng/ml of t-PA, aggregation was decreased significantly in response to ADP and to collagen. In contrast to canine platelets, aggregation of human platelets exposed to 250 U/ml of SK was markedly decreased. The diminished aggregatory response of human platelets exposed to t-PA or SK was both time- and concentration-dependent. It appeared to be dependent on generation of active plasmin as evidenced by depletion of α 2-antiplasmin and plasminogen and by preservation of normal aggregation when platelets were exposed to either plasminogen activator and aprotinin concomitantly. The disparate effects of SK on aggregation of canine and human platelets appeared to be related to the more modest activation of plasminogen by SK in canine compared with human blood. Results of surface radiolabelling and immunoblotting experiments indicated that exposure of human platelets to t-PA led to diminution of membrane associated fibrinogen. Thus, exposure of platelets to pharmacologic concentrations of plasminogen activators appears to influence platelet function by a plasmin-dependent mechanism resulting in reduction of membrane associated fibrinogen.