Abstract 19956: Differential Effects of Clopidogrel on Platelet Activation Measured by Annexin Binding vs. Platelet Aggregation: An Explanation for Rapid Antithrombotic Properties Even in the Presence of Clopidogrel “Resistance”
Background: The antithrombotic effect of clopidogrel is related primarily to the inhibition of platelet aggregation (PA). However, modulation of coagulation system activity by platelets may also be a critical determinant of the propensity for in vivo thrombosis. The latter may provide an explanation for the protective influence of clopidogrel despite the high rates of “resistance” reported in the literature based on platelet function measurements.
Methods: 44 stable CAD pts. and 27 pts. undergoing PCI on 325mg aspirin therapy received a 600mg clopidogrel loading dose. PA (ADP, collagen, epinephrine-induced light transmittance aggregometry); and procoagulant property by annexin binding (flow cytometry) were measured at baseline, 2, 6–8 and 24 h post-dosing. Resistance was defined as ≤10% absolute change in 20μM ADP-induced PA between baseline and 6–8 hours post dose. Student t-test was used to compare resistant (R) vs. responsive (RES) pts.
Results: Clopidogrel inhibited annexin binding in both R and RES pts (Figure). At 2 h there was a minimal effect of clopidogrel on PA (5 and 22% inhibition in R vs. RES pts, respectively) whereas annexin binding was markedly inhibited in both groups (82% and 60% inhibition, respectively).
Conclusions: Unlike inhibition of platelet aggregation, clopidogrel markedly and rapidly inhibits platelet procoagulant activity in both “resistant” and responsive CAD patients after a 600 mg load. The present findings are consistent with the beneficial clinical effects observed within 2 h of loading despite a mild effect on PA. These findings, in part, may also explain why the majority of “resistant” patients identified by platelet function measurements don't suffer thrombotic events. This study introduces a novel parameter beyond PA inhibition, a marker that has been used in all previous translational research studies to examine clopidogrel's antithrombotic effect.
- © 2010 by American Heart Association, Inc.