Age-related changes in the hemostatic system.

The increased incidence of arterial thromboembolism in the elderly has prompted investigation of age-related changes in the hemostatic system. Aging is associated with increased plasma levels of fibrinogen, factor VII and factor VIII, which have been shown to be risk factors for thrombotic disease in five large epidemiological studies. An increased responsiveness to different aggregating stimuli, elevated levels of beta-thromboglobulin and an increased production of thromboxane A2 were reported in the platelets of the elderly. These alterations are associated with modifications of platelet membrane lipid composition (namely an increase in the cholesterol/phospholipid ratio and a decrease in linoleic acid) with possible related changes in membrane fluidity. Moreover, a decrease in the number of platelet prostacyclin and thromboxane A2 receptors was observed with aging. Fibrinolytic activity is impaired in the elderly, probably due to an increase in plasminogen activator inhibitor 1. Interestingly, hypercoagulability has been demonstrated by an increase in the activation markers of the coagulation cascade (mainly fibrinopeptide A and prothrombin activation fragment F 1 + 2). Finally, clinical and experimental evidence suggests that endothelium could play a central role in hemostatic alterations which determine a thrombophilic state in the elderly.