Platelet Activation and Clopidogrel Effects on ADP‐Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5032873/ https://www.ncbi.nlm.nih.gov/pubmed/27615120 http://dx.doi.org/10.1111/jvim.14568 |
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author | Li, R.H.L. Stern, J.A. Ho, V. Tablin, F. Harris, S.P. |
author_facet | Li, R.H.L. Stern, J.A. Ho, V. Tablin, F. Harris, S.P. |
author_sort | Li, R.H.L. |
collection | PubMed |
description | 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 PGE (1)‐treated platelets had a similar level of pVASP as PGE (1)‐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. |
format | Online Article Text |
id | pubmed-5032873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-50328732016-09-30 Platelet Activation and Clopidogrel Effects on ADP‐Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3 Li, R.H.L. Stern, J.A. Ho, V. Tablin, F. Harris, S.P. J Vet Intern Med SMALL ANIMAL 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 PGE (1)‐treated platelets had a similar level of pVASP as PGE (1)‐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. John Wiley and Sons Inc. 2016-09-12 2016 /pmc/articles/PMC5032873/ /pubmed/27615120 http://dx.doi.org/10.1111/jvim.14568 Text en Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | SMALL ANIMAL Li, R.H.L. Stern, J.A. Ho, V. Tablin, F. Harris, S.P. Platelet Activation and Clopidogrel Effects on ADP‐Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3 |
title | Platelet Activation and Clopidogrel Effects on ADP‐Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3
|
title_full | Platelet Activation and Clopidogrel Effects on ADP‐Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3
|
title_fullStr | Platelet Activation and Clopidogrel Effects on ADP‐Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3
|
title_full_unstemmed | Platelet Activation and Clopidogrel Effects on ADP‐Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3
|
title_short | Platelet Activation and Clopidogrel Effects on ADP‐Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3
|
title_sort | platelet activation and clopidogrel effects on adp‐induced platelet activation in cats with or without the a31p mutation in mybpc3 |
topic | SMALL ANIMAL |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5032873/ https://www.ncbi.nlm.nih.gov/pubmed/27615120 http://dx.doi.org/10.1111/jvim.14568 |
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