title: Management of Bleeding With Non-Vitamin K Antagonist Oral Anticoagulants in the Era of Specific Reversal Agents.
abstract: Vitamin K antagonists are commonly used by clinicians to provide anticoagulation to patients who have or are at risk of having thrombotic events. In addition to familiarity with the dosing and monitoring of vitamin K antagonists, clinicians are accustomed to using vitamin K if there is a need to reverse the anticoagulant effect of vitamin K antagonists. There are now 4 new non-vitamin K antagonist oral anticoagulants (NOACs) that are attractive alternatives to vitamin K antagonists. Despite similar or lower rates of serious bleeding with NOACs in comparison with warfarin, there is a pressing need for strategies to manage bleeding when it does occur with NOACs and to reverse the pharmacological effect of these agents if needed. Important steps in minimizing bleeding risks with NOACs include dose adjustment of the agents in the setting of renal dysfunction and avoidance of the concomitant use of other antithrombotic agents if feasible. Laboratory measurement of the anticoagulant effect of NOACs is best accomplished with specialized assays, although some of the more widely available coagulation tests can provide information that is potentially useful to clinicians. Nonspecific hemostatic agents such as prothrombin complex concentrates and recombinant factor VIIa can be used to reverse the effect of NOACs. More specific reversing agents include the approved humanized monoclonal antibody fragment idarucizumab for reversing the effects of dabigatran, the investigational factor Xa decoy andexanet alfa, and the synthetic small molecule ciraparantag. Both andexanet and ciraparantag have been reported to reverse the effects of the anti-Xa NOACs (rivaroxaban, apixaban, and edoxaban), and a number of other anticoagulant agents in common clinical use, as well.
authors.affiliation: From TIMI Study Group, Cardiovascular Medicine Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. cruff@partners.org.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Ruff
authors.affiliation: From TIMI Study Group, Cardiovascular Medicine Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.affiliation: From TIMI Study Group, Cardiovascular Medicine Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
mesh_terms: D000284:Administration, Oral; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000991:Antithrombins / Q000009:adverse effects* / Q000627:therapeutic use; D001120:Arginine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D000069604:Dabigatran / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D015942:Factor VIIa / Q000627:therapeutic use; D015951:Factor Xa / Q000009:adverse effects / Q000627:therapeutic use; D065427:Factor Xa Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D010949:Plasma; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D000069552:Rivaroxaban / Q000009:adverse effects / Q000627:therapeutic use; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000991:Antithrombins; D001779:Blood Coagulation Factors; D065427:Factor Xa Inhibitors; D006490:Hemostatics; C580915:PRT064445; D010879:Piperazines; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D011994:Recombinant Proteins; D013844:Thiazoles; C025667:prothrombin complex concentrates; C522181:apixaban; D001120:Arginine; C000594745:idarucizumab; D000069552:Rivaroxaban; C103587:recombinant FVIIa; D015942:Factor VIIa; D015951:Factor Xa; D000069604:Dabigatran; C552171:edoxaban; C000593571:PER977
keywords: anticoagulants; atrial fibrillation; hemorrhage; venous thromboembolism