Diabetes mellitus - A hypercoagulable state

Eighty percent of patients with diabetes mellitus die a thrombotic death. S eventy-five percent of these deaths is due to cardiovascular complications, and the remainder is due to cerebrovascular events and peripheral vascular complications. Vascular endothelium, the primary defense against thrombosi s, is abnormal in diabetes. Endothelial abnormalities undoubtedly play a ro le in the enhanced activation of platelets and cloning factors seen in diab etes. Coagulation activation markers, such as prothrombin activation fragme nt 1+2 and thrombin-antithrombin complexes, are elevated in diabetes. The p lasma levels of many clotting factors including fibrinogen, factor VII, fac tor VIII, factor SI. factor XII, kallikrein, and von Willebrand factor are elevated in diabetes. Conversely, the level of the anticoagulant protein C (PC) is decreased. The fibrinolytic system, the primary means of removing c lots, is relatively inhibited in diabetes due to abnormal clot structures t hat are more resistant to degradation and an increase in plasminogen activa tor inhibitor type 1 (PAI-1). Increased circulating platelet aggregates, in creased platelet aggregation in response to platelet agonists, increased pl atelet contractile Force (PCF), and the presence of higher plasma levels of platelet release products, such as beta -thromboglobulin, platelet factor 4, and thromboxane beta (2), demonstrate platelet hyperactivity in diabetes . This constellation of findings supports the clinical observation that dia betes is a hypercoagulable state. This article briefly reviews the publishe d evidence for this conclusion and the putative roles played by hyperglycem ia and hyperinsulinemia in its development. (C) 2001 Elsevier Science Inc. All rights reserved.