title: The effect of a loading dose (300 mg) of clopidogrel on platelet function in patients with peripheral arterial disease.
abstract: 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.
authors.affiliation: Department Clinical Biochemistry, Royal Free University College School of Medicine, University of London, Royal Free Campus, UK.
authors.forename: Miltiadis
authors.initials: M
authors.lastname: Matsagas
authors.forename: I Anita
authors.initials: IA
authors.lastname: Jagroop
authors.forename: George
authors.initials: G
authors.lastname: Geroulakos
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
mesh_terms: 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
chemical_list: C109734:P2RY11 protein, human; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D012701:Serotonin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin