title: 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.
  
  
  OBJECTIVE
  To compare the effect of oral clopidogrel and aspirin (ASA) on equine platelet function.
  
  
  METHODS
  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 ± 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
  Clopidogrel effectively decreases ADP-induced platelet aggregation in horses, and could have therapeutic applications for equine diseases associated with platelet activation.
authors.affiliation: Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. brainard@uga.edu
authors.forename: B M
authors.initials: BM
authors.lastname: Brainard
authors.forename: K L
authors.initials: KL
authors.lastname: Epstein
authors.forename: D
authors.initials: D
authors.lastname: LoBato
authors.forename: S
authors.initials: S
authors.lastname: Kwon
authors.forename: M G
authors.initials: MG
authors.lastname: Papich
authors.forename: J N
authors.initials: JN
authors.lastname: Moore
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D019540:Area Under Curve; D001241:Aspirin / Q000493:pharmacokinetics / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D000077144:Clopidogrel; D018592:Cross-Over Studies; D005260:Female; D006736:Horses / Q000097:blood / Q000502:physiology*; D008297:Male; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010976:Platelet Count / Q000662:veterinary; D011446:Prospective Studies; D011897:Random Allocation; D012701:Serotonin / Q000097:blood*; D013927:Thrombosis / Q000517:prevention & control / Q000662:veterinary; D013929:Thromboxane B2 / Q000096:biosynthesis* / Q000097:blood; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D012701:Serotonin; D013929:Thromboxane B2; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin