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 prophylactically and therapeutically, in a wide variety of conditions. Although the dosage used has also varied, it is now suggested that lower doses are as efficacious and probably safer than higher doses. Part of the problem in determining the amount to be used is that aspirin not only inhibits the formation of the proaggregatory thromboxane A2 in the platelet, at any dose, but also that it interferes with the production of prostacyclin (antiaggregatory) by the endothelial cells in a dose-dependent manner. Previously, utilizing a hamster cheek pouch preparation, we demonstrated that platelets would adhere to intact endothelium, in vivo, after an otherwise ineffectual dose of thrombin if the glycosaminoglycans of endothelial cells that produce antithrombin activity were first neutralized by protamine. Reported here is the effect of aspirin on the platelet thrombi produced by thrombin in this manner. Aspirin was found to inhibit platelet thrombosis by thrombin in low doses (optimum dose 2.5 mg/kg body weight), but at higher doses the aspirin was less effective. Actually, the higher doses of aspirin promoted platelet thrombus formation by thrombin even in the absence of protamine. 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 thrombogenicity of the higher doses of aspirin. The results of these experiments in the hamster suggest that the optimum dosage of aspirin in the clinical treatment of prophylaxis of thrombosis in human patients would be 160 mg.(ABSTRACT TRUNCATED AT 250 WORDS)
Shanberge
J N
JN
Department of Clinical Pathology, William Beaumont Hospital, Royal Oak, MI 48073.
Kajiwara
Y
Y
Quattrociocchi-Longe
T
T
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000502:physiology*; D016285:Iloprost / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011479:Protamines / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D013927:Thrombosis / Q000139:chemically induced / Q000517:prevention & control
D011479:Protamines; D013917:Thrombin; D016285:Iloprost; D001241:Aspirin