title: Antidotes for novel oral anticoagulants: current status and future potential.
abstract: The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. Their main disadvantage is currently the absence of a specific reversal agent. Dabigatran's, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. These agents are currently in premarketing studies.
authors.affiliation: From the Department of Haematology, Worcestershire Royal Hospital, Worcester, United Kingdom (M.C.); and Department of Haematology, St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada (M.A.C.). mark.crowther@nhs.net.
authors.forename: Mark
authors.initials: M
authors.lastname: Crowther
authors.affiliation: From the Department of Haematology, Worcestershire Royal Hospital, Worcester, United Kingdom (M.C.); and Department of Haematology, St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada (M.A.C.).
authors.forename: Mark A
authors.initials: MA
authors.lastname: Crowther
mesh_terms: D000284:Administration, Oral; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects*; D000931:Antidotes / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D003029:Coagulants / Q000627:therapeutic use*; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D010879:Piperazines / Q000627:therapeutic use; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants; D000931:Antidotes; D003029:Coagulants; D010879:Piperazines; D001120:Arginine; C000594745:idarucizumab; C000593571:PER977
keywords: anticoagulants; apixaban; dabigatran; factor VIIa; hemorrhage; prothrombin complex concentrate; rivaroxaban