Sex difference in the risk of recurrent venous thrombosis: a detailed analysis in four European cohorts

Background Previous analyses reported a higher risk of recurrent venous thrombosis in men than women. Objectives We aimed to assess the risk of recurrence in men compared with women whilst taking female reproductive risk factors (oral contraception, postmenopausal hormone therapy and pregnancy) into account. In addition, we hypothesized that the sex difference in venous thrombosis was related to F9 Malmö, an X‐linked prothrombotic factor. Methods In four pooled European cohorts (CARROT study, Glasgow, UK; CVTE study, Cambridge, UK; AUREC study, Vienna, Austria; and LETS follow‐up study, Leiden, the Netherlands), the risk of recurrent venous thrombosis was calculated in men, women with reproductive risk factors and women without reproductive risk factors at the time of their first venous thrombosis. F9 Malmö was genotyped and carriers and non‐carriers contrasted. Results In total, 2185 patients with a first venous thrombosis, 1043 men and 1142 women, were included. Overall, men had a 2.8‐fold (95% confidence interval [CI], 2.2–3.4) higher risk of recurrent venous thrombosis than women. This risk was 5.2‐fold (95% CI, 3.5–7.7) higher in men than in women with reproductive risk factors, and 2.3‐fold (95% CI, 1.7–3.2) higher in men than in women without reproductive risk factors. No difference in risk of recurrence was found for carriers vs. non‐carriers of F9 Malmö. Conclusion Men experienced a recurrent venous thrombosis twice as often as women without reproductive risk factors. These findings indicate that men have a higher intrinsic risk of venous thrombosis than women, which is partly masked by female reproductive risk factors. The sex difference cannot be explained by F9 Malmö.