Diabetes mellitus: a hypercoagulable state.
Eighty percent of patients with diabetes mellitus die a thrombotic death. Seventy-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 thrombosis, is abnormal in diabetes. Endothelial abnormalities undoubtedly play a role in the enhanced activation of platelets and clotting factors seen in diabetes. Coagulation activation markers, such as prothrombin activation fragment 1+2 and thrombin-anti-thrombin complexes, are elevated in diabetes. The plasma levels of many clotting factors including fibrinogen, factor VII, factor VIII, factor XI, 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 clots, is relatively inhibited in diabetes due to abnormal clot structures that are more resistant to degradation and an increase in plasminogen activator inhibitor type 1 (PAI-1). Increased circulating platelet aggregates, increased platelet aggregation in response to platelet agonists, increased platelet contractile force (PCF), and the presence of higher plasma levels of platelet release products, such as beta-thromboglobulin, platelet factor 4, and thromboxane B(2), demonstrate platelet hyperactivity in diabetes. This constellation of findings supports the clinical observation that diabetes is a hypercoagulable state. This article briefly reviews the published evidence for this conclusion and the putative roles played by hyperglycemia and hyperinsulinemia in its development.
Departments of Internal Medicine and Pathology, Medical College of Virginia, Virginia Commonwealth University, Box 980230, Richmond, VA 23298-0230, USA. mcarr@hsc.vcu.edu
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D000925:Anticoagulants / Q000097:blood; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000401:mortality / Q000503:physiopathology*; D006801:Humans; D019851:Thrombophilia / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D013927:Thrombosis / Q000401:mortality
D000925:Anticoagulants; D001779:Blood Coagulation Factors