Effects of Clopidogrel and Aspirin on Platelet Aggregation, Thromboxane Production, and Serotonin Secretion in Horses

Background Critically ill horses are susceptible to thrombotic disease, which might be related to increased platelet reactivity and activation. Objectives To compare the effect of oral clopidogrel and aspirin (ASA) on equine platelet function. Animals Six healthy adult horses. Methods Horses received clopidogrel (2 mg/kg PO q24h) or ASA (5 mg/kg PO q24h) for 5 days in a prospective randomized cross-over design. Platelet aggregation responses to adenosine diphosphate (ADP) and collagen via optical aggregometry, and platelet secretion of serotonin (5HT) and production of thromboxane B(2) (TXB(2)) by ELISA were evaluated. In horses receiving clopidogrel, high-performance liquid chromatography analysis for clopidogrel and its carboxylic-acid metabolite SR 26334 was performed. Results SR 26334 was identified in all clopidogrel-treated horses, although the parent compound was not detected. Clopidogrel resulted in decreases in ADP-induced platelet aggregation persisting for 120 hours after the final dose. ADP-induced platelet aggregation decreased from a baseline of 70.2 +/- 14.7% to a minimum of 15.9 +/- 7.7% 24 hours after the final dose (P < .001). Collagen-induced aggregation decreased from a baseline of 93 +/- 9.5% to a minimum of 70.8 +/- 16.9% 48 hours after the final dose (P < .001). ASA did not decrease platelet aggregation with either agonist. ASA decreased serum TXB(2) from a baseline value of 1310 +/- 1045 to 128 +/- 64 pg/mL within 24 hours (P < .01). Conclusions and Clinical Importance Clopidogrel effectively decreases ADP-induced platelet aggregation in horses, and could have therapeutic applications for equine diseases associated with platelet activation.