Clopidogrel attenuates coated-platelet production in patients undergoing elective coronary catheterization.
BACKGROUND
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.


RESULTS
We enrolled 27 patients undergoing elective coronary angiography. A total of 3 blood samples were taken from eligible patients: baseline, 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 microM adenosine diphosphate (ADP). Baseline levels of coated-platelets were 40.0% +/- 14.3% (mean +/- 1 SD). 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 microM and 11.2% AR; 19.1% RR for 6 microM).


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.
Norgard
Nicholas B
NB
School of Pharmacy and Pharmaceutical Sciences, Department of Pharmacy Practice, University at Buffalo, Buffalo, NY 14260-1200, USA. nicknorgard@mac.com
Saya
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S
Hann
C L
CL
Hennebry
T A
TA
Schechter
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Dale
G L
GL
D000244:Adenosine Diphosphate; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006328:Cardiac Catheterization; D000077144:Clopidogrel; D017023:Coronary Angiography; D003435:Crotalid Venoms; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000097:blood; D058925:Receptors, Purinergic P2Y12; D013917:Thrombin; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D003435:Crotalid Venoms; D005343:Fibrinolytic Agents; D037181:Lectins, C-Type; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; C028890:convulxin; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013917:Thrombin; D013988:Ticlopidine