Platelet Activation and Clopidogrel Effects on ADP-Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1619-1629
Number of pages11
JournalJournal of Veterinary Internal Medicine
Volume30
Issue number5
DOIs
StatePublished - Sep 1 2016

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clopidogrel
adenosine diphosphate
platelet activation
Platelet Activation
Adenosine Diphosphate
Cats
cats
mutation
Mutation
Blood Platelets
platelet aggregation
Platelet Aggregation
P-Selectin
Alprostadil

Keywords

  • Cat
  • Hypertrophic cardiomyopathy
  • Platelet hyper-reactivity
  • Thromboembolism

ASJC Scopus subject areas

  • veterinary(all)

Cite this

@article{16ab88e911044db99342203d4004211a,
title = "Platelet Activation and Clopidogrel Effects on ADP-Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3",
abstract = "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.",
keywords = "Cat, Hypertrophic cardiomyopathy, Platelet hyper-reactivity, Thromboembolism",
author = "Li, {Ronald H L} and Stern, {Joshua A} and V. Ho and Fern Tablin and Harris, {S. P.}",
year = "2016",
month = "9",
day = "1",
doi = "10.1111/jvim.14568",
language = "English (US)",
volume = "30",
pages = "1619--1629",
journal = "Journal of Veterinary Internal Medicine",
issn = "0891-6640",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Platelet Activation and Clopidogrel Effects on ADP-Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3

AU - Li, Ronald H L

AU - Stern, Joshua A

AU - Ho, V.

AU - Tablin, Fern

AU - Harris, S. P.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

AB - 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.

KW - Cat

KW - Hypertrophic cardiomyopathy

KW - Platelet hyper-reactivity

KW - Thromboembolism

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DO - 10.1111/jvim.14568

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C2 - 27615120

AN - SCOPUS:84987814238

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JO - Journal of Veterinary Internal Medicine

JF - Journal of Veterinary Internal Medicine

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