Factor V Leiden in women: a thrombotic risk factor or an evolutionary advantage?

Factor V Leiden is a common gain-of-function gene mutation resulting in a genetic predisposition to thromboembolic complications. Growing evidence in the literature indicates an interaction between factor V Leiden thrombophilia and acquired prothrombotic conditions such as contraceptive use or hormone replacement therapy, resulting in an increased risk of venous thromboembolism (VTE). Similarly, when combined with the prothrombotic influence of pregnancy, women who are carriers of factor V Leiden are faced with an increased risk of adverse pregnancy outcomes, including VTE, pre-eclampsia, fetal loss, placental abruption, and fetal growth restriction. The results of the most important meta-analyses on the relationship between inherited (factor V Leiden) and acquired thrombophilia in women are analyzed in this review, along with the possible evolutionary role of this mutation.