Phenylbutazone inhibition of equine platelet function

Nonsteroidal anti-inflammatory drugs impair platelet aggregation and secretion in man, pigs, and rabbits and inhibit platelet thromboxane/prostaglandin synthesis. The present investigation studied the effects of phenylbutazone on platelet aggregation and bleeding times in the horse. Aggregation responses to adenosine diphosphate and collagen were markedly impaired 15 minutes and 2 hours after treatment, but 4 hours after treatment, platelet responses approximated those prior to treatment. The in vivo effect of phenylbutazone correlated with its plasma concentrations. Phenylbutazone, like aspirin, appeared to exert its effect by inhibiting thromboxane/prostaglandin synthesis, because thrombin-induced malondialdehyde formation was inhibited. However, unlike aspirin, free arachidonate-induced malondialdehyde synthesis was reduced but not eliminated, which suggested that phenylbutazone may have more than one site of action. Although collagen-induced platelet aggregation was impaired, a response was still present, and bleeding times were not altered by phenylbutazone treatment. To account for these findings, it is proposed that equine platelets can respond to collagen by thromboxane/prostaglandin independent pathways. The physiologic and pathophysiologic importance of these findings is discussed.