Clinical aspects of the relationship between oral contraceptives and abnormalities of the hemostatic system: relation to the development of cardiovascular disease.

Epidemiologic evidence has established that oral contraceptives increase the risk of both arterial and venous thromboembolic disease. This is dose related in the case of the estrogen component for both arterial and venous events and in the case of progestogens for arterial events. It is probable that the increased rate of thromboembolic events caused by estrogen is related to hypercoagulability. Plasma levels of several clotting factors have been shown to be elevated in oral contraceptive users, and this increase is graduated according to the dose of estrogen. In pregnancy, factor VIIc is increased after cold activation of plasma at 4 degrees C overnight. Likewise, in users of oral contraceptives, both factors VIIc and XIIc are increased, which suggests a direct effect of factor XIIc on the extrinsic system. In men, the risk of ischemic heart disease is strongly and independently related to factor VIIc and fibrinogen levels; thus it is possible that in women taking oral contraceptives, the mechanism of risk is similarly mediated. There is a good case for factor VIIc as the index of flux in the coagulation system and hence of a hypercoagulable state, and indeed it may directly contribute to the generation of thrombin. This article examines the available evidence on clotting factor activity in the risk of cardiovascular disease in oral contraceptive users.