Use of PER977 to Reverse the Anticoagulant Effect of Edoxaban

Among 80 healthy persons who had received a single dose of edoxaban, the whole-blood clotting time was reduced significantly more rapidly in those who received the novel small molecule PER977 than in controls who were not given PER977. To the Editor: New target-specific oral anticoagulants are limited by the lack of a proven reversal agent. PER977 (Perosphere) is a small, synthetic, water-soluble, cationic molecule that is designed to bind specifically to unfractionated heparin and low-molecular-weight heparin through noncovalent hydrogen bonding and charge–charge interactions (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). 1 , 2 PER977 binds in a similar way to the new oral factor Xa inhibitors, edoxaban, rivaroxaban and apixaban, and to the oral thrombin inhibitor, dabigatran. In thromboelastographic studies and rat-tail–transection bleeding assays, PER977 has been shown to reverse anticoagulation with . . .