Use of PER977 to Reverse the Anticoagulant Effect of Edoxaban

• Published in: The New England journal of medicine Vol. 371; no. 22; pp. 2141 - 2142
• Main Authors: Ansell, Jack E, Bakhru, Sasha H, Laulicht, Bryan E, Steiner, Solomon S, Grosso, Michael, Brown, Karen, Dishy, Victor, Noveck, Robert J, Costin, James C
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 27.11.2014
• Subjects: Anticoagulants; Arginine - analogs & derivatives; Arginine - pharmacokinetics; Arginine - pharmacology; Blood coagulation; Blood Coagulation - drug effects; Clotting; Factor Xa Inhibitors; Heparin Antagonists - pharmacokinetics; Heparin Antagonists - pharmacology; Humans; Pharmaceuticals; Pharmacology; Piperazines - pharmacokinetics; Piperazines - pharmacology; Pyridines - antagonists & inhibitors; Thiazoles - antagonists & inhibitors
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMc1411800

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 . . .