EFFECT OF ASPIRIN AND ILOPROST ON ADHESION OF PLATELETS TO INTACT ENDOTHELIUM IN-VIVO

Aspirin has been used for the prevention of platelet thrombi, both pro phylactically and therapeutically, in a wide variety of conditions. Al though the dosage used has also varied, it is now suggested that lower doses are as efficacious and probably safer than higher doses. Part o f the problem in determining the amount to be used is that aspirin not only inhibits the formation of the proaggregatory thromboxane A, in t he platelet, at any dose, but also that it interferes with the product ion of prostacyclin (antiaggregatory) by the endothelial cells in a do se-dependent manner. Previously, utilizing a hamster cheek pouch prepa ration, we demonstrated that platelets would adhere to intact endothel ium, in vivo, after an otherwise ineffectual dose of thrombin if the g lycosaminoglycans of endothelial cells that produce antithrombin activ ity were first neutralized by protamine. Reported here is the effect o f aspirin on the platelet thrombi produced by thrombin in this manner. Aspirin was found to inhibit platelet thrombosis by thrombin in low d oses (optimum dose 2.5 mg/kg body weight), but at higher doses the asp irin was less effective. Actually, the higher doses of aspirin promote d platelet thrombus formation by thrombin even in the absence of prota mine. Infusion of iloprost, an analog of prostacyclin, also prevented platelet thrombus formation by protamine and thrombin with or without the administration of aspirin, and this infusion overcame the thrombog enicity of the higher doses of aspirin. The results of these experimen ts in the hamster suggest that the optimum dosage of aspirin in the cl inical treatment of prophylaxis of thrombosis in human patients would be 160 mg. If higher doses of aspirin (350 mg or greater) are used, th e simultaneous administration of a prostacyclin analog, such as ilopro st, may decrease its thrombogenicity.