The use of direct oral anticoagulants in the secondary prevention of venous thromboembolism in patients with severe thrombophilia: communication from the ISTH SSC Subcommittee on Physiological Anticoagulants and Thrombophilia.

Direct oral anticoagulants (DOACs) are the first-line anticoagulants for the secondary prevention of venous thromboembolism (VTE). However, patients with severe inherited thrombophilias represent a group in whom the efficiency and safety of DOACs is poorly studied. In this communication, we focus on the utility of DOACs in the secondary prevention of VTE in patients with severe thrombophilia. Current evidence is based only on cohort or single-center studies, and poor data are available on compliance of the patients in the studies. Analysis of the studies suggested that full-dose DOACs and vitamin K antagonists have a similar efficacy and bleeding risk in the secondary prevention of VTE in patients with thrombophilia, with a low hazard ratio for recurrent VTE calculated from cohort studies for DOAC vs warfarin, ranging from 0.3 to 0.75. We wish to highlight that treatment failure is greater in those with severe forms of protein S deficiency (below 20%) and possibly in antithrombin deficiency type II heparin-binding site homozygous Budapest 3. In summary, the current approach to using DOACs in patients with severe thrombophilia is dependent on clinical judgment and experience. Limited evidence suggests that for those with severe thrombophilias, full-dose DOACs have similar utility as vitamin K antagonists. We recommend caution in using low-dose DOACs due to lack of evidence. Ideally, large randomized multicenter studies are required to develop a reliable treatment algorithm.