Effects of clopidogrel and aspirin on platelet aggregation, thromboxane production, and serotonin secretion in horses.

Abstract

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 p.o. q24h) or ASA (5 mg/kg p.o. 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 &#xb1; 14.7% to a minimum of 15.9 &#xb1; 7.7% 24 hours after the final dose (P < .001). Collagen-induced aggregation decreased from a baseline of 93 &#xb1; 9.5% to a minimum of 70.8 &#xb1; 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 &#xb1; 1045 to 128 &#xb1; 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.