Higher risk of venous thrombosis during early use of oral contraceptives in women with inherited clotting defects

Background: Results of recent studies show that the risk for venous thrombosis is highest during initial oral contraceptive use. This suggests a subgroup of females who are at immediate risk of thrombosis when exposed to oral contraceptives. Objective: To determine whether women with inherited clotting defects who use oral contraceptives develop venous thrombosis at an earlier stage than do those without inherited clotting defects. Methods: Analysis of the data from the Leiden Thrombophilia Study, a population-based case-control study with data on duration of oral contraceptive use and recently detected genetic coagulation disorders. Patients had a first episode of objectively proven deep vein thrombosis. Patients and controls were considered thrombophilic when they had protein C deficiency, protein S deficiency, antithrombin deficiency, factor V leiden mutation, or prothrombin 20210 A mutation. Results: Risk of developing deep vein thrombosis was greatest in the first 6 months and the first year of oral contraceptive use. Compared with prolonged use, the risk of developing deep vein thrombosis was 3-fold higher in the first 6 months of use (95% confidence interval [CI], 0.6-14.8) and 2-fold higher in the first year of use (95% CI, 0.6-6.1). Patients who developed venous thrombosis in the early periods of use were more often thrombophilic. Among women with thrombophilia, the risk of developing deep vein thrombosis during the first 6 months of oral contraceptive use (compared with prolonged use) was increased 19-fold (95% CI, 1.9-175.7), and in the first year of use, it was increased Ii-fold (95% CI, 2.1-57.3). Conclusions: Women with inherited clotting defects who use oral contraceptives develop venous thrombosis not only more often but also sooner than do those without inherited clotting defects. Venous thrombosis in the first period of oral contraceptive use might indicate the presence of an inherited clotting defect.