Clopidogrel Attenuates Coated-platelet Production in Patients Undergoing Elective Coronary Catheterization

INTRODUCTION:Coated-platelets are a subclass of highly thrombotic activated platelets with an enhanced ability to generate thrombin. Excessive numbers of coated-platelets are believed to increase thrombotic risk. A previous report demonstrated that P2Y12 inhibition in vitro attenuates coated-platelet formation. The aim of this study was to determine the effect clopidogrel has on coated-platelet formation. METHODS AND RESULTS:We enrolled 27 patients undergoing elective coronary angiography. A total of 3 blood samples were taken from eligible patientsbaseline, 24-hour postclopidogrel (preangiography), and 6-hour postangiography. Coated-platelet levels, expressed as percentage of total platelets, were determined with convulxin and thrombin with or without 1.5 or 6 μM adenosine diphosphate (ADP). Baseline levels of coated-platelets were 40.0% ± 14.3% (mean ± 1SD). After clopidogrel exposure, the coated-platelet level was 32.8% ± 13.6%, representing a significant 7.2% absolute reduction (AR) (17.8% relative reduction (RR); P < 0.0001). Clopidogrel significantly lowered the convulxin, thrombin plus ADP coated-platelet production (11.0% AR; 20.1% RR for 1.5 μM and 11.2% AR; 19.1% RR for 6 μM). CONCLUSIONS:This is the first report on the impact of in vivo administration of a P2Y12 antagonist on coated-platelet formation. The significance of a partial attenuation in coated-platelet potential has yet to be determined, but this could represent a new antithrombotic mechanism of clopidogrel beyond inhibition of ADP-induced aggregation.