Management of hereditary thrombophilia has become more restrained and evidence-based. The 2023 American Society of Hematology guidelines recommend against routine long-term prophylactic anticoagulation for asymptomatic individuals with common inherited thrombophilias (such as heterozygous factor V Leiden or the prothrombin G20210A mutation), favoring instead short courses of prophylaxis only during transient high-risk periods like surgery or immobilization. When anticoagulation is needed, DOACs appear to be a safe and effective alternative to warfarin — even in higher-risk states such as homozygous factor V Leiden or prothrombin mutations, where studies show no significant difference in recurrent VTE or major bleeding.
The critical exception is antiphospholipid syndrome, where DOACs should not be used in high-risk (triple-positive) patients — the TRAPS trial found rivaroxaban inferior to warfarin, with more arterial thrombotic events — so vitamin K antagonists remain standard. For refractory or obstetric antiphospholipid syndrome, adjuncts such as hydroxychloroquine and, in selected cases, complement inhibition are under investigation. The broader message is that thrombophilia testing should be selective, since it seldom changes management.
Further reading: ASH 2023 thrombophilia testing guideline (Middeldorp et al., Blood Advances 2023); DOACs in high-risk hereditary thrombophilia (Dan et al., 2025); TRAPS rivaroxaban in antiphospholipid syndrome.