Platelet-activating factor and not thromboxane A2 is an important mediator of endotoxin-induced platelet aggregation in equine heparinised whole blood in vitro.

Abstract

Endotoxin has previously been shown to induce platelet aggregation in equine heparinised whole blood. This study aimed to determine whether platelet-activating factor or products of cyclo-oxygenase metabolism (thromboxane A2 or prostaglandins) were important in mediating the response of platelets to endotoxin. The effects of the following drugs on endotoxin-induced aggregation were investigated: aspirin, flunixin meglumine and carprofen (non-steroidal anti-inflammatory drugs); CV-3988 and WEB2086 (platelet-activating factor receptor antagonists); quinacrine (phospholipase A2 inhibitor). The effects of quinacrine on platelet aggregation in citrated platelet-rich plasma induced by ADP and platelet-activating factor were also investigated. CV-3988 and WEB2086 caused a concentration-dependent inhibition of endotoxin-induced aggregation. The non-steroidal anti-inflammatories were without effect except flunixin meglumine which produced a small inhibition of endotoxin-induced aggregation. Quinacrine had a similar effect to the platelet-activating factor antagonists, but also non-competitively inhibited platelet aggregation in citrated platelet-rich plasma. It is concluded that platelet-activating factor is a critical mediator of endotoxin-induced platelet aggregation in the horse, but that products of cyclo-oxygenase metabolism are not of importance.