Platelet Cyclooxygenase Expression in Normal Dogs

Abstract

Background: Human platelets express both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Variation in COX-2 expression could be a mechanism for variable response to aspirin. Hypothesis/Objectives: The hypotheses were that circulating canine platelets express COX-1 and COX-2, and that aspirin alters COX expression. The objective was to identify changes in platelet COX expression and in platelet function caused by aspirin administration to dogs. Animals: Eight female, intact hounds. Methods: A single population, repeated measures design was used to evaluate platelet COX-1 and COX-2 expression by flow cytometry before and after aspirin (10 mg/kg Q12h for 10 days). Platelet function was analyzed via PFA-100 ® (collagen/epinephrine), and urine 11-dehydro-thromboxane B 2 (11-dTXB 2) was measured and normalized to urinary creatinine. Differences in COX expression, PFA-100 ® closure times, and urine 11-dTXB 2: creatinine ratio were analyzed before and after aspirin administration. Results:: Both COX-1 and COX-2 were expressed in canine platelets. COX-1 mean fluorescent intensity (MFI) increased in all dogs, by 250% (range 63-476%), while COX-2 expression did not change significantly (P = 0.124) after aspirin exposure, with large interindividual variation. PFA-100 ® closure times were prolonged and urine 11-dTXB 2 concentration decreased in all dogs after aspirin administration. Conclusions and Clinical Importance: Canine platelets express both COX isoforms. After aspirin exposure, COX-1 expression increased despite impairment of platelet function, while COX-2 expression varied markedly among dogs. Variability in platelet COX-2 expression should be explored as a potential mechanism for, or marker of, variable aspirin responsiveness. © 2011 by the American College of Veterinary Internal Medicine.