title: Current and developing strategies for monitoring and reversing direct oral anticoagulants in patients with non-valvular atrial fibrillation.
abstract: OBJECTIVE
  In light of the increasing clinical utilization of the direct oral anticoagulants (DOACs) among patients with non-valvular atrial fibrillation, this review evaluates strategies for monitoring and reversing the anticoagulant effect of these agents.
  
  
  METHODS
  We summarize the data currently available for laboratory monitoring and reversal of DOACs. Relevant literature was identified using search terms pertaining to oral anticoagulants, reversal agents, and laboratory monitoring using Pubmed, clinicaltrials.gov, and abstracts from recent major cardiovascular meetings.
  
  
  RESULTS
  Significant user appeal for the DOACs stems from the reliable pharmacokinetics of these agents, which render routine laboratory monitoring unnecessary for general use, as well as lower rates of bleeding as compared to warfarin. However, readily available laboratory tests have not been clinically validated for use with these agents. The ability to measure the anticoagulant effect of a DOAC in selected situations (e.g. serious bleeding, overanticoagulation, emergent procedures, and compliance monitoring) remains an unmet clinical need. Further, there is a paucity of data to guide treatment in patients receiving DOACs who experience a serious hemorrhage.
  
  
  CONCLUSIONS
  While evidence-based recommendations cannot be definitively provided for management of DOAC-related bleeding events at present, several targeted reversal agents are currently in development, and hold promise for solving this important clinical problem.
authors.affiliation: a Cardiology Division , Massachusetts General Hospital , Boston , MA , USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Sarma
authors.affiliation: b Department of Medicine, Cardiovascular Division , Brigham and Women's Hospital , Boston , MA , USA.|c TIMI Study Group, Cardiovascular Medicine , Brigham and Women's Hospital , Boston , MA , USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D012720:Severity of Illness Index; D054556:Venous Thromboembolism / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D006493:Heparin
keywords: Anticoagulant reversal; Atrial fibrillation; Direct oral anticoagulants; Major bleeding