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J Vet Intern Med ; 30(5): 1619-1629, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27615120

RESUMEN

BACKGROUND: Clopidogrel is commonly prescribed to cats with perceived increased risk of thromboembolic events, but little information exists regarding its antiplatelet effects. OBJECTIVE: To determine effects of clopidogrel on platelet responsiveness in cats with or without the A31P mutation in the MYBPC3 gene. A secondary aim was to characterize variability in feline platelet responses to clopidogrel. ANIMALS: Fourteen healthy cats from a Maine Coon/outbred mixed Domestic cat colony: 8 cats homozygous for A31P mutation in the MYPBC3 gene and 6 wild-type cats without the A31P mutation. METHODS: Ex vivo study. All cats received clopidogrel (18.75 mg PO q24h) for 14 days. Before and after clopidogrel treatment, adenosine diphosphate (ADP)-induced P-selectin expression was evaluated. ADP- and thrombin-induced platelet aggregation was measured by optical aggregometry (OA). Platelet pVASP and ADP receptor response index (ARRI) were measured by Western blot analysis. RESULTS: Platelet activation from cats with the A31P mutation was significantly (P = .0095) increased [35.55% (18.58-48.55) to 58.90% (24.85-69.90)], in response to ADP. Clopidogrel treatment attenuated ADP-induced P-selectin expression and platelet aggregation. ADP- and PGE1 -treated platelets had a similar level of pVASP as PGE1 -treated platelets after clopidogrel treatment. Clopidogrel administration resulted in significantly lower ARRI [24.13% (12.46-35.50) to 11.30% (-7.383 to 23.27)] (P = .017). Two of 13 cats were nonresponders based on OA and flow cytometry. CONCLUSION AND CLINICAL IMPORTANCE: Clopidogrel is effective at attenuating platelet activation and aggregation in some cats. Cats with A31P mutation had increased platelet activation relative to the variable response seen in wild-type cats.


Asunto(s)
Adenosina Difosfato/toxicidad , Proteínas Portadoras/metabolismo , Gatos/genética , Activación Plaquetaria/fisiología , Trombosis/veterinaria , Ticlopidina/análogos & derivados , Animales , Proteínas Portadoras/genética , Enfermedades de los Gatos/inducido químicamente , Gatos/fisiología , Clopidogrel , Regulación de la Expresión Génica/fisiología , Predisposición Genética a la Enfermedad , Genotipo , Mutación , Activación Plaquetaria/genética , Inhibidores de Agregación Plaquetaria/farmacología , Trombosis/inducido químicamente , Ticlopidina/farmacología
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