Expert Commentary

Q.Are oral contraceptives safe for women with a thrombophilic defect?

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A.No. In this retrospective family cohort study from the Netherlands, women who had protein S, protein C, or antithrombin deficiency had a greater baseline risk of venous thromboembolism (VTE), and the risk increased when they used combination oral contraceptives.

Expert Commentary

This report confirms the greater risk of VTE in women with protein S, protein C, or antithrombin deficiency, compared with unaffected women. When they used oral contraceptives (OCs), women with 1 or more of these deficiencies had 10 times the risk of VTE that unaffected women had. And when they had additional thrombophilic deficiencies—such as a second deficiency of protein S or C or antithrombin; factor V Leiden; or prothrombin G20210A—their risk of VTE was further amplified.

Because women with thrombophilic deficiency have a higher baseline risk of VTE, they developed VTE while taking OCs—or during pregnancy, another high-risk setting—at a younger age than their non–OC-using or nonpregnant counterparts, but the overall incidence of VTE during their reproductive years did not increase.

Family cohort framework facilitated study of rare mutations

A retrospective family cohort study is a good design to control for events in similar populations with relatively rare mutational occurrences. This study was adequately powered for its major observations, but lost power and significance when it focused on women with multiple thrombophilic deficiencies. Nevertheless, it confirmed the greater risk of VTE with OC use in thrombophilic women, and clarified the absolute risk of VTE over a woman’s reproductive life, which remains fairly stable because women with thrombophilic deficiencies are at such high risk to begin with.

The study also demonstrated that women with a thrombophilic deficiency have a high risk of multiple deficiencies.

Findings may not be applicable to women with other deficiencies

When a woman has a deficiency other than protein S, protein C, or antithrombin, these findings may not be valid. For example, factor V Leiden mutation is strongly associated with VTE in OC users. It is unclear whether the observation of a stable absolute risk of VTE in OC users would have held up if factor V Leiden was one of the major deficiencies studied.

Bottom line: Pay attention to the family history

This study highlights the importance of a good family history. Women who have family members known to have a thrombophilic deficiency should avoid OCs or be tested for all deficiencies and given oral contraceptives only if they prove to be free of deficiencies. These tests are very expensive and are not cost-effective in a general population screen.

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