Cyclooxygenase Expression and Platelet Function in Healthy Dogs Receiving Low-Dose Aspirin

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 (1mg/kg Q24hours PO, 10days). 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, -29.7136.1%) (P=.047) and 72% on Day 10 (range, -0.37210%) (P<.001). Platelet COX-2 MFI increased significantly by 34% (range, -29.2270%) on Day 3 (P=.003) and 74% (range, -19.7226%) 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.