Clopidogrel inhibits platelet-leukocyte interactions and thrombin receptor agonist peptide-induced platelet activation in patients with an acute coronary syndrome.
OBJECTIVE
We sought to characterize the effects of clopidogrel on the activation of circulating platelets, the activation and aggregation of ex vivo platelets, and the interactions with leukocytes in patients with a non-ST-segment elevation in acute coronary syndromes (ACS).


BACKGROUND
The significant benefits of clopidogrel in cardiovascular trials suggest that blockage of the P2Y(12) receptor may be associated with important biologic consequences.


METHODS
Blood samples obtained from 23 ACS patients before and 24 h after a loading dose of clopidogrel (300 mg) were analyzed by whole-blood flow cytometry, light transmission aggregometry in platelet-rich plasma, and plasma enzyme-linked immunoassays. A thrombin receptor agonist peptide (TRAP) and adenosine diphosphate (ADP) were used as agonists. Normal individuals pretreated with aspirin served as controls.


RESULTS
Clopidogrel attenuated platelet aggregation to both ADP (10 micromol/l) and TRAP (10 micromol/l) by 22% and P-selectin expression by 16% and 25%, respectively. The drug decreased the excess platelet-monocyte and platelet-neutrophil conjugates found in the blood of ACS patients (p < 0.01) and prevented their formation ex vivo with agonist stimulation. Plasma levels of soluble CD40L were reduced by 27% (p < 0.001) and of soluble P-selectin by 15% (p < 0.001).


CONCLUSIONS
Clopidogrel attenuates the agonist effects of ADP and TRAP on platelet secretion, aggregation, and formation of platelet-monocyte and platelet-neutrophil conjugates in patients with ACS. These effects may all contribute to the clinical benefits of the drug in these syndromes.
Xiao
Zihui
Z
Department of Medicine, Montreal Heart Institute, and University of Montreal, Montreal, Quebec, Canada.
Théroux
Pierre
P
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D001792:Blood Platelets / Q000502:physiology*; D023201:CD40 Ligand / Q000097:blood; D000077144:Clopidogrel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
D019007:P-Selectin; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; C086309:thrombin receptor peptide SFLLRNP; D023201:CD40 Ligand; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin