Thrombophilic mechanisms of OCs

Oral contraceptives (OCs) have minor effects on procoagulant and anticoagulant 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 acquired changes can be statistically significant between OC users and nonusers, there is no evidence that they are clinically significant. In contrast, increased risk of venous thrombosis has been associated with inherited deficiencies in protein S and protein C, which are both natural anticoagulant proteins. In addition, activated protein C (APC) resistance can occur via a mutation of factor V, known as factor V Leiden, which 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 factor V Leiden positivity was associated with a 35-fold increased risk of venous thrombosis compared with controls. However, the absolute risk of venous thrombosis in this group was low; the incidence of venous thrombosis was 28.5 events per 10,000 women-years in women with both factors (in comparison, pregnancy was associated with an incidence of 5.9 per 10,000 women-years). Even if venous thrombosis could be totally prevented in OC users with the Leiden mutation, there would be little impact on the total number of cases of venous thrombosis; therefore, routine screening for factor V Leiden or APC resistance prior to starting women on OCs does not seem to be warranted.