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 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 AE 14.7% to a minimum of 15.9 AE 7.7% 24 hours after the final dose (P o .001). Collagen-induced aggregation decreased from a baseline of 93 AE 9.5% to a minimum of 70.8 AE 16.9% 48 hours after the final dose (P o .001). ASA did not decrease platelet aggregation with either agonist. ASA decreased serum TXB 2 from a baseline value of 1310 AE 1045 to 128 AE 64 pg/mL within 24 hours (P o .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.

Effects of Firocoxib, Flunixin Meglumine, and Phenylbutazone on Platelet Function and Thromboxane Synthesis in Healthy Horses

“…A decrease in thromboxane synthesis would be expected to inhibit platelet reactivity; however, our study demonstrated that despite a decrease in thromboxane synthesis, platelet function was not inhibited. A similar phenomenon was reported previously in horses when treated with another NSAID, aspirin . This phenomenon has been reported in other species and is known as aspirin resistance.…”

“…Following clot formation, samples were centrifuged at 1,800 × g for 8 minutes at room temperature. The serum was collected and within 1 hour of collection was stored at −20°C for no longer than 3 months until analyzed using a commercially available ELISA kit (Thromboxane B 2 EIA Kit; Cayman Chemical, MI) that has been previously used for analysis of equine serum thromboxane B 2 . Prior to analysis, the serum was thawed to room temperature.…”

Cardiovascular, Colloid Osmotic Pressure, and Hemostatic Effects of 2 Formulations of Hydroxyethyl Starch in Healthy Horses

“…Optical platelet aggregation18 was performed at baseline, time 0, and 8 hours using final concentrations of ADP19 and collagen18 of 15 μM and 15 μg/mL, respectively, for activation as previously described 21…”

Complications of intravenous catheterization in horses

“…Other anticoagulants (phenoprocoumon, warfarin, clopridogel) have been studied but are difficult to administer in a practice setting due to monitoring requirements or they have only been evaluated in a research setting (Scott et al, 1980;Bubeck et al, 2005;Brainard et al, 2011;Brainard et al, 2012). Recombinant tissue plasminogen activator has recently been evaluated in vivo and in vitro for its thrombolytic effects in healthy horses.…”