Platelet adhesion and aggregation in diabetes mellitus.
Platelets from diabetic patients show both increased platelet adhesiveness and sensitivity to aggregating agents. Plasma levels of the platelet-active von Willebrand Factor and the closely related factor-VIII antigen are significantly elevated, while factor VIII procoagulant activity is not. This may reflect either intravascular coagulation or disproportionate production or degradation. Plasma factors that enhance ADP-induced platelet aggregation are found in 50% of unselected male diabetics. Activity is clearly demonstrated only when plasma is added immediately prior to adding subthreshold doses of ADP to platelet-rich plasma obtained from control subjects. Systematic investigations of the molecular nature of such factors and their interactions with platelets are in progress. In platelets obtained from diabetic subjects, we have previously found increased sensitivity to the aggregating effects of arachidonic acid, and increased synthesis of immunoreactive prostaglandin E-like material. More recent studies have shown that platelets obtained from diabetic subjects are less sensitive to the antiaggregatory effects of imidazole, a thromboxane synthetase inhibitor. These observations suggest that increased synthesis of the labile aggregating substance thromboxane A2 also occurs in platelets obtained from diabetics. Collectively, these platelet and plasma abnormalities may contribute to accelerated vascular disease of diabetes. Prospective studies using antiplatelet agents are presently underway or in the planning stages in diabetics to explore their potential beneficial effects.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001779:Blood Coagulation Factors / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood*; D005169:Factor VIII / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D010972:Platelet Activating Factor; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation / Q000187:drug effects; D014841:von Willebrand Factor / Q000502:physiology
D001095:Arachidonic Acids; D001779:Blood Coagulation Factors; D007093:Imidazoles; D007328:Insulin; D010972:Platelet Activating Factor; D014841:von Willebrand Factor; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D005169:Factor VIII