Effects of clopidogrel and aspirin on platelet aggregation, thromboxane production, and serotonin secretion in horses.
Abstract: 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.
Copyright © 2010 by the American College of Veterinary Internal Medicine.
Publication Date: 2010-12-08 PubMed ID: 21143302DOI: 10.1111/j.1939-1676.2010.0647.xGoogle Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study aimed to compare the effects of clopidogrel and aspirin on platelet function in horses, potentially paving the way for better treatment options for equine diseases associated with platelet activation.
Methodology
- The research was conducted on six healthy adult horses using a prospective randomized cross-over design.
- The subjects received either clopidogrel or aspirin, administered orally on a daily basis for 5 days.
- The team of researchers employed optical aggregometry to measure platelet aggregation in response to adenosine diphosphate (ADP) and collagen.
- They also estimated platelet secretion of serotonin and production of thromboxane B2 through an ELISA (Enzyme-Linked Immunosorbent Assay).
- The presence of clopidogrel and its metabolite SR 26334 in the horse’s system was evaluated using high-performance liquid chromatography analysis.
Findings
- The metabolite SR 26334 was found in all clopidogrel-treated horses but the parent compound was not detected.
- Reductions in ADP-induced platelet aggregation were observed in the horses treated with clopidogrel, persisting for 120 hours after the last dose.
- The study found that clopidogrel reduced ADP-induced platelet aggregation from a baseline of 70.2% down to 15.9% 24 hours after the final dose.
- Furthermore, the collagen-induced platelet aggregation in horses, which had a baseline of 93% was decreased to as low as 70.8% 48 hours after the last dose.
- However, the research noted that aspirin did not decrease platelet aggregation with either agonist, referring to ADP and Collagen.
- On a different mode of efficacy, aspirin significantly decreased serum thromboxane B2 from a baseline value of 1310 to 128 pg/mL within 24 hours.
Conclusion
- The research concluded that clopidogrel can effectively reduce ADP-induced platelet aggregation in horses.
- This suggests the potential of using clopidogrel in therapeutic applications for treating equine diseases associated with platelet activation.
Cite This Article
APA
Brainard BM, Epstein KL, LoBato D, Kwon S, Papich MG, Moore JN.
(2010).
Effects of clopidogrel and aspirin on platelet aggregation, thromboxane production, and serotonin secretion in horses.
J Vet Intern Med, 25(1), 116-122.
https://doi.org/10.1111/j.1939-1676.2010.0647.x Publication
Researcher Affiliations
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. brainard@uga.edu
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Area Under Curve
- Aspirin / pharmacokinetics
- Aspirin / pharmacology
- Blood Platelets / drug effects
- Blood Platelets / physiology
- Clopidogrel
- Cross-Over Studies
- Female
- Horses / blood
- Horses / physiology
- Male
- Platelet Activation / drug effects
- Platelet Aggregation Inhibitors / pharmacology
- Platelet Count / veterinary
- Prospective Studies
- Random Allocation
- Serotonin / blood
- Thrombosis / prevention & control
- Thrombosis / veterinary
- Thromboxane B2 / biosynthesis
- Thromboxane B2 / blood
- Ticlopidine / analogs & derivatives
- Ticlopidine / pharmacokinetics
- Ticlopidine / pharmacology
Citations
This article has been cited 2 times.- Serpa PBS, Brooks MB, Divers T, Ness S, Birschmann I, Papich MG, Stokol T. Pharmacokinetics and Pharmacodynamics of an Oral Formulation of Apixaban in Horses After Oral and Intravenous Administration. Front Vet Sci 2018;5:304.
- Epstein KL, Bergren A, Giguère S, Brainard BM. Cardiovascular, colloid osmotic pressure, and hemostatic effects of 2 formulations of hydroxyethyl starch in healthy horses. J Vet Intern Med 2014 Jan-Feb;28(1):223-33.
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