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Keywords:

  • Aspirin resistance;
  • Canine;
  • COX ;
  • PFA-100;
  • Thromboxane

Background

Low-dose aspirin is used to prevent thromboembolic complications in dogs, but some animals are nonresponsive to the antiplatelet effects of aspirin (“aspirin resistance”).

Hypothesis/Objectives

That low-dose aspirin would inhibit platelet function, decrease thromboxane synthesis, and alter platelet cyclooxygenase (COX) expression.

Animals

Twenty-four healthy dogs.

Methods

A repeated measures study. Platelet function (PFA-100 closure time, collagen/epinephrine), platelet COX-1 and COX-2 expression, and urine 11-dehydro-thromboxane B2 (11-dTXB2) were evaluated before and during aspirin administration (1 mg/kg Q24 hours PO, 10 days). Based on prolongation of closure times after aspirin administration, dogs were divided into categories according to aspirin responsiveness: responders, nonresponders, and inconsistent responders.

Results

Low-dose aspirin increased closure times significantly (62% by Day 10, P < .001), with an equal distribution among aspirin responsiveness categories, 8 dogs per group. Platelet COX-1 mean fluorescent intensity (MFI) increased significantly during treatment, 13% on Day 3 (range, −29.7–136.1%) (P = .047) and 72% on Day 10 (range, −0.37–210%) (P < .001). Platelet COX-2 MFI increased significantly by 34% (range, −29.2–270%) on Day 3 (P = .003) and 74% (range, −19.7–226%) on Day 10 (P < .001). Urinary 11-dTXB2 concentrations significantly (P = .005, P < .001) decreased at both time points. There was no difference between aspirin responsiveness and either platelet COX expression or thromboxane production.

Conclusions and Clinical Importance

Low-dose aspirin consistently inhibits platelet function in approximately one-third of healthy dogs, despite decreased thromboxane synthesis and increased platelet COX expression in most dogs. COX isoform expression before treatment did not predict aspirin resistance.