Unlike warfarin, non-vitamin K antagonist oral anticoagulants lack reversal agents for administration in the case of severe bleeding or perioperative management. Idarucizumab is a monoclonal antibody fragment that was developed to reverse the anticoagulant effects of the direct thrombin inhibitor dabigatran. In this safety and efficacy study, idarucizumab was tested in a cohort of patients on dabigatran who either required an urgent surgical procedure or who had developed major bleeding. In an analysis of 90 patients (51 with hemorrhage and 39 requiring surgery) 5g of intravenous idarucizumab was administered to assess the impact on coagulation measures that included dilute thrombin time and ecarin clotting time. Idarucizumab proved safe and effective with a median maximum percentage reversal of clotting measures of 100% within minutes of administration. Concentrations of free dabigatran remained essentially undetectable at 24 hours in 79% of patients. Clinical hemostasis was achieved at a median of 11.4 hours in the hemorrhagic group and 3 (7.7%) patients in the surgical group had mild or moderately impaired hemostasis.
In this small study, idarucizumab appears to rapidly reverse the anticoagulant effects of the direct thrombin inhibitor dabigatran. Similar agents are in final stage development for both rivaroxaban and apixaban and may further improve the usability of non-vitamin K antagonist anticoagulants.
Summarized by Hussain Contractor and Steven M. Bradley
Pollack CV Jr, Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kamphuisen PW, Kreuzer J, Levy JH, Sellke FW, Stangier J, Steiner T, Wang B, Kam CW, Weitz J. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015 Aug 6;373(6):511-20.