Oral contraceptives have been linked to an increased incidence of thrombovascular disease. This may be mediated by their effects on the haemostatic system. An increase in the activity of coagulation Factors VII, X and fibrinogen occur with pill usage. Increased Factor VII levels are dependent on both the oestrogen and progestogen component of the oral contraceptive. A reduction in antithrombin III levels has also been observed in some but not all studies. Increased fibrinolysis has also been shown in oral contraceptive users which should balance the changes in the coagulation pathway. The increase in fibrinolytic potential is thought to be due to a decrease in the levels of plasminogen activator inhibitor I combined with an increase in the levels of plasminogen; tissue plasminogen activator antigen is decreased in most studies. The increased levels of endpoints of coagulation and fibrinolysis in pill users indicate that enhanced activity of both systems is occurring in vivo. The increased coagulation activity appears to be balanced by the rise in fibrinolytic activity, so preserving haemostatic balance. Enhanced platelet activity has also been shown in women taking oral contraceptives. Thrombus formation can result, however, when local vascular wall damage exists, or when other risk factors for thrombo-embolism, such as older age and smoking, coexist and create a local activation resulting in a thrombus. In these situations, the small differences in levels of coagulation factors in women taking different oral contraceptive formulations may be important. Pills containing the lowest doses of oestrogen (20 micrograms ethinyloestradiol) have shown the least changes in haemostatic factors. The progestogen component of the pill modifies the effect of oestrogen on the haemostatic system.
PIP: Numerous studies have investigated the mechanisms whereby, in some healthy women, oral contraceptives (OCs) can cause thrombosis. In healthy OC users, the coagulation and fibrinolytic systems are in dynamic balance and control fibrin deposition within the vascular compartment. The production of fibrin can be initiated by either the intrinsic or extrinsic coagulation pathway. Factors such as light smoking in older women or an asymptomatic borderline deficiency in a coagulation inhibitor may cause thrombogenic changes in the hemostatic system in women with a normal blood flow and a healthy vascular endothelium. OC usage is associated with an increase in the activity of coagulation factors VII, X, and fibrinogen; a reduction in antithrombin III levels has been shown in some studies. The Factor V Leiden mutation explains 20-50% of cases of venous thromboembolism. Low doses of ethinyl estradiol combined with less androgenic third-generation progestogens were thought to represent little or no risk of thromboembolic or cardiovascular disease, which may have led to overprescribing of these formulations to women with possible risk factors for thromboembolic disease. Pills containing 20 mcg of ethinyl estradiol have shown the least changes in hemostatic factors. The progestogen component of the OC modifies the effect of estrogen on the hemostatic system. The recent epidemiologic reports suggest that all pills carry an increased thrombotic risk, and each woman requesting OCs should undergo careful clinical screening.