In vitro Effects of combined Administration of Eptifibatide and Anticoagulants on Thrombin induced Platelet Aggregation after high versus low Coagulant Activation of Platelet Rich Plasma

Abstract

Aim of our study was to compare effects of eptifibatide and anticoagulants on platelet aggregation and thrombin generation under low versus high coagulant challenge in tissue factor-activated platelet rich plasma. We used a Model allowing simultaneous determination of the time course of platelet aggregation and thrombin generation in the presence of eptifibatide and anticoagulants after extrinsic activation of plasma. Eptifibatide exerted a dose dependent anti-aggregating effect which reached its Maximum at 1000 ng/Ml. Under low coagulant challenge the antiaggregating effect was significantly higher compared to results obtained under high coagulant challenge, but also reached its Maximum at 1000 ng/Ml. Addition of eptifibatide revealed no influence after both high and low coagulant challenge on thrombin generation under our experimental conditions. Eptifibatide prolonged dose dependently the lag phase until the onset of platelet aggregation under low coagulant but not under high coagulant challenge. Under both high and low coagulant challenge UH, LMWH, and rH dose dependently decreased thrombin generation, but had no influence on platelet aggregation. Combination of eptifibatide and anticoagulants resulted in significant additive prolongation of the lag phase, More pronounced under low coagulant challenge. Combination of eptifibatide and anticoagulants under high coagulant challenge had a significant synergistic inhibitory effect on platelet aggregation. In contrast, under low coagulant challenge addition of anticoagulants to plasma that contained eptifibatide did not add to inhibition of platelet aggregation. Combined addition of eptifibatide and anticoagulants to plasma did not significantly add to the decrease of thrombin generation at high coagulant challenge. Interestingly, under low coagulant challenge combination of eptifibatide and LMWH resulted in significantly reduced thrombin generation compared to Measurements in the absence of eptifibatide. Combined administration of eptifibatide with rH, or UH under low coagulant challenge did not result in reduced thrombin generation.

Our in vitro experiments support the notion that combined application of eptifibatide and anticoagulants Might be beneficial in atherosclerotic disease to palliate the high thrombogenic challenge of ruptured atherosclerotic plaques.