Platelet-activating factor and not thromboxane A(2) is an important mediator of endotoxin-induced platelet aggregation in equine heparinised whole blood in vitro

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 cyclooxygenase metabolism (thromboxane A(2) 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 A(2) 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, bur that products of cyclooygenase metabolism are not of importance.