Increased platelet prostaglandin and thromboxane synthesis in diabetes mellitus

Platelets obtained from some diabetic patients show enhanced in vitro platelet aggregation. These studies were designed to determine if platelets obtained from diabetic subjects manifest increased metabolism of arachidonic acid to labile aggregating substances, such as thromboxane A2 (TXA2), and if they play a role in the enhanced platelet aggregation. Arachidonic acid stimulated TXA2 synthesis, as determined via radioimmunoassay of its stable metabolite TXB2, was significantly greater (p less than 0.01, n = 12) in platelet-rich plasma obtained from diabetic compared to matched controls. Arachidonic acid stimulated TXB2 synthesis in the diabetic platelet-rich plasma was positively correlated with the ambient fasting plasma glucose (r = 0.61, p less than 0.02, n = 15). Platelet aggregation induced by arachidonic acid (0.4-0.8 mM) was inhibited significantly less by 13-azaprostanoic acid (p less than 0.04, n = 14), an antagonist of the actions of prostaglandin H2 or TXA2 on platelets, compared to matched controls. We conclude that platelets obtained from some diabetic subjects manifest increased metabolism of arachidonic acid to labile aggregating substances which may contribute to the enhanced platelet aggregation.