Efficacy and safety of anti-Xa direct oral anticoagulants vs. warfarin in patients homozygous for Factor V Leiden and prothrombin G20210A mutations

Factor V Leiden (FVL) and prothrombin G20210A mutation (PGM) are the most common types of inherited thrombophilia, predisposing to increased venous thromboembolism (VTE) risk. The homozygous and compound heterozygous forms of these mutations are extremely rare. While direct oral anticoagulants (DOACs) have replaced vitamin K antagonists (VKAs) as the primary treatment for VTE, data on their use in patients with high-risk hereditary thrombophilia are limited. To compare the efficacy and safety of DOACs vs. VKA in patients with high-risk hereditary thrombophilia, including FVL and PGM. This retrospective cohort study included adults with homozygous/compound heterozygous FVL and/or PGM who experienced a thrombotic event between 2000 and 2022. The primary outcome was the incidence of recurrent thrombosis in patients with high-risk inherited thrombophilia treated with DOACs versus VKAs. The secondary outcome included a comparison of rates of bleeding complications between these groups. The types of bleeding were defined according to the ISTH criteria. Of 56 patients included 28 received DOACs and 28 received VKAs. There was no significant difference in recurrent VTE rates (1/28, 3.6% DOAC group vs. 0/28, 0% VKA group) or major bleeding (1/28, 3.6% DOAC group vs. 1/28, 3.6% VKA group). This is the largest cohort of patients with high-risk hereditary thrombophilia, providing valuable insights into DOAC use in this group. The findings suggest that DOACs may represent an effective and safe alternative to VKAs. Further research is warranted to confirm these results and optimize anticoagulant management in this challenging patient group.Graphical AbstractThis graphical abstract comparing the efficacy and safety of DOACs versus Vitamin VKA in patients with high-risk hereditary thrombophilia. The central image depicts a stylized blood vessel with thrombotic formations, representing the underlying thrombophilic condition. On either side, circular diagrams show treatment outcomes for 28 patients in each group. The DOAC group had a 3.6% recurrent VTE rate and a 3.6% bleeding rate. The VKA group showed a 0% recurrent VTE rate and a 3.6% bleeding rate