The effect of a loading dose (300 mg) of clopidogrel on platelet function in patients with peripheral arterial disease.
Clopidogrel acts on the P2Y12 adenosine diphosphate (ADP) purinergic receptors on human platelets. The aim of this study was to establish if a loading dose of clopidogrel inhibits platelet activation in patients with peripheral arterial disease (PAD). Two indices of platelet activation were considered: platelet shape change (PSC) and aggregation. Citrated blood was collected from ten PAD patients who were not on aspirin, at baseline (0 hours) and 2 and 4 hours after these patients ingested a loading dose (300 mg) of clopidogrel. ADP (5 micromo/L)-induced platelet aggregation in whole blood was inhibited after 2 hours (free platelet count, 47% +/- 19% vs. 68% +/- 15%; p < or = 0.001) and 4 hours (47% +/- 19% vs. 66% +/- 16%; p < or = 0.001). There was also a significant inhibition of 5- hydroxytryptamine (SHT, 5.0 micromol/L)-induced platelet aggregation at 2 hours. This trend was also observed for 10-micomol/L ADP-induced aggregation. ADP (0.3-0.4 micromol/L)-induced PSC was significantly inhibited at 4 hours (increase in median platelet volume, 6.3%, 1.8-10.7 vs. 1.2%, 0-5.3; p = 0.01). 5HT (0.5 micromol/L)-induced PSC at 4 hours was also significantly inhibited (8.1, 5.3-10.6 vs. 3.0, 0-8.2; p = 0.03). A loading dose of clopidogrel (300 mg) inhibits platelet activation in PAD patients, as early as 2 hours. To the authors' knowledge, no other study considered the effect of a loading dose of clopidogrel in PAD.
Matsagas
Miltiadis
M
Department Clinical Biochemistry, Royal Free University College School of Medicine, University of London, Royal Free Campus, UK.
Jagroop
I Anita
IA
Geroulakos
George
G
Mikhailidis
Dimitri P
DP
D000368:Aged; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D000077144:Clopidogrel; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000188:drug therapy; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use
C109734:P2RY11 protein, human; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D012701:Serotonin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin