title: Monitoring and reversal of direct oral anticoagulants.
abstract: Although the direct oral anticoagulants (DOACs) do not require routine monitoring and reduce bleeding compared with warfarin, there are special circumstances in which laboratory measurement or reversal of their anticoagulant effect may be indicated. The dilute thrombin time and ecarin-based assays are able to quantify dabigatran across a broad range of concentrations, but are not widely available. A normal thrombin time excludes clinically relevant levels and a normal activated partial thromboplastin time probably excludes excess levels of dabigatran. Factor Xa inhibitors may be quantified with an anti-Xa assay calibrated with drug-specific standards. A normal prothrombin time probably excludes excess levels of rivaroxaban and edoxaban, but not apixaban. Patients with minor and moderate DOAC-associated bleeding can be treated with supportive care and general hemostatic measures. Nonspecific reversal agents (eg, prothrombin complex concentrate, activated prothrombin complex concentrate) are of unproven benefit, carry a risk of thrombosis, and should be reserved for severe bleeding. Specific reversal agents, such as idarucizumab (a monoclonal antibody fragment that binds dabigatran) and andexanet alfa (a recombinant factor Xa variant that binds factor Xa inhibitors but lacks coagulant activity), are in clinical development.
authors.affiliation: Departments of Medicine and Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: Adam
authors.initials: A
authors.lastname: Cuker
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Deborah
authors.initials: D
authors.lastname: Siegal
mesh_terms: D000284:Administration, Oral; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D001780:Blood Coagulation Tests; D000069604:Dabigatran / Q000627:therapeutic use; D015942:Factor VIIa / Q000627:therapeutic use; D015951:Factor Xa / Q000627:therapeutic use; D065427:Factor Xa Inhibitors / Q000737:chemistry; D006470:Hemorrhage; D006487:Hemostasis; D006801:Humans; D010314:Partial Thromboplastin Time; D010879:Piperazines / Q000627:therapeutic use; D011516:Prothrombin / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D000069552:Rivaroxaban / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D013918:Thrombin Time
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants; D001779:Blood Coagulation Factors; D065427:Factor Xa Inhibitors; C580915:PRT064445; D010879:Piperazines; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D011994:Recombinant Proteins; D013844:Thiazoles; C025667:prothrombin complex concentrates; C522181:apixaban; D011516:Prothrombin; D001120:Arginine; C000594745:idarucizumab; D000069552:Rivaroxaban; C103587:recombinant FVIIa; D015942:Factor VIIa; D015951:Factor Xa; D000069604:Dabigatran; C552171:edoxaban; C000593571:PER977