Perioperative Management of Patients on Factor XI or Factor XIa Inhibitors

Factor XI and XIa inhibitors - which include antisense oligonucleotides, monoclonal antibodies, and small peptidomimetic molecules - represent a new class of anticoagulants that inhibit the intrinsic pathway and attenuate thrombosis without disruption of hemostasis, thus making them potentially ideal anticoagulants to use in perioperative settings. Surgical data in patients with Factor XI deficiency (including severe Factor XI deficiency) reveal a phenotype that suggests uncomplicated hemostasis, especially in surgical areas of low fibrinolytic activity. Periprocedural data from completed Phase 2 clinical trials demonstrate two observations: 1) for primary venous thromboprophylaxis of patients undergoing major orthopedic surgery who are at risk of major bleeding, strategies to inhibit FXI result in a lower risk of venous thromboembolism and lower clinically relevant bleeding compared to current recommended therapy such as enoxaparin; 2) for patients on long-term FXI inhibitors undergoing elective procedures, there is potential for simpler and potentially safer periprocedural paradigms without interruption of FXI inhibitors compared to the simplified and standardized approach with direct oral anticoagulants, at least for low and (some) moderate bleed risk procedures. Further work, including tailored perioperative prospective management studies, targeted FXI inhibitor reversal strategies, and assays to assess the anticoagulant effects of FXI inhibitors in perioperative settings are needed.