The role of GP IIb/IIIa inhibitors on the fibrinolytic resistance of platelet-fibrin thrombi

摘要

The presence of platelets increases the fibrinolytic resistance of thrombi. When activated, platelets secrete PAI-1 and α{sub}2-antiplasmin and induce clot retraction. The search for potent antiplatelet agents has led to inhibitors of theplatelet receptor GP IIb/IIIa, one of which is ReoPro (c7E3 Fab; abciximab). The effect of ReoPro on rt-PA-induced fibrinolysis was studied using an in vitro whole blood reperfusion model. When ReoPro was administered simultaneously with rt-PA at a wallshear rate of 500 s{sup}(-1), it had no effect on the rate of fibrinolysis. rt-PA was found to lyse preformed gel-filtered platelet-fibrin substrates containing fixed platelets quicker than those containing normal platelets. ReoPro was shown to blockplatelet-fibrin interactions under arterial flow. Hence, we hypothesized (and are currently testing) that a combination of a GP IIb/IIIa inhibitor preincubated with the substrate, and a fibrinolytic drug injected with the flow, may hasten lysis ofplatelet-fibrin substrates under well-defined hemodynamic conditions. ReoPro may prove a necessary adjunctive treatment during thrombolytic therapy of platelet-rich thrombi. [Supported by NIH grant HL-54089.]