THROMBOPHILIC MECHANISMS OF OCS

Oral contraceptives (OCs) have minor effects on procoagulant and antic oagulant factors. Clotting factor changes that are associated with the use of low-androgenic OCs include a 10% to 20% increase in fibrinogen , variable effects on factor VII, an increase in fibrinopeptide A, and a 10% to 20% decrease in protein S (in comparison, levels of protein S decrease approximately 70% during pregnancy). Although these acquire d changes can be statistically significant between OC users and nonuse rs, there is no evidence that they are clinically significant. In cont rast, increased risk of venous thrombosis has been associated with inh erited deficiencies in protein S and protein C, which are both natural anticoagulant proteins. In addition, activated protein C (APC) resist ance can occur via a mutation of factor V, known as factor V Leiden, w hich is present in 5% of the general population and 20-40% of patients with venous thrombosis. In one study, the combination of OC use and f actor V Leiden positivity was associated with a 35-fold increased risk of venous thrombosis compared with controls. However, the absolute ri sk of venous thrombosis in this group was low; the incidence of venous thrombosis was 28.5 events per 10,000 woman-years in women with both factors (in comparison, pregnancy was associated with an incidence of 5.9 per 10,000 woman-years). Even if venous thrombosis could be totall y prevented in OC users with the Leiden mutation, there would be littl e impact on the total number of cases of venous thrombosis; therefore, routine screening for factor V Leiden or APC resistance prior to star ting women on OCs does not seem to be warranted.