title: Idarucizumab and factor Xa reversal agents: role in hospital guidelines and protocols.
abstract: As expected with all antithrombotic agents, there is a risk of bleeding complications in patients receiving direct oral anticoagulants (DOACs) because of the DOAC itself, acute trauma, invasive procedures, or underlying comorbidities. For many bleeding events, a prudent course of action will be to withdraw the DOAC, then "wait and support" the patient, with the expectation that the bleeding event should resolve with time. Likewise, DOAC therapy may be interrupted ahead of a planned procedure, the stopping time being dependent on the agent involved and the patient's renal function. However, urgent reversal of anticoagulation is required in patients with serious or life-threatening bleeding or in those requiring urgent surgery or procedures. Novel specific reversal agents, either under development or recently approved, will need to be incorporated into local anticoagulation reversal protocols. For dabigatran-treated patients, idarucizumab recently has been approved for clinical use in cases of life-threatening or uncontrolled bleeding or when patients require emergency surgery or urgent procedures, both associated with a high risk of bleeding. As clinical experience with individual specific reversal agents grows, their roles in managing major bleeding events in DOAC-treated patients will become better defined. Future research, as well as ongoing use of idarucizumab, should help establish when it is appropriate to re-dose with idarucizumab, coadminister with prothrombin complex concentrates, or re-initiate DOAC after idarucizumab use. Ongoing trials should help identify the appropriate doses and expected durations of effect for andexanet alfa and ciraparantag, which are likely to vary depending on the individual oral anticoagulants.
authors.affiliation: Department of Medicine-Thrombosis and Hemostasis, Leiden University Medical Center, Netherlands. Electronic address: m.v.huisman@lumc.nl.
authors.forename: Menno V
authors.initials: MV
authors.lastname: Huisman
authors.affiliation: Department of Pharmacy Services, Brigham and Women's Hospital, Boston, Mass.
authors.forename: John
authors.initials: J
authors.lastname: Fanikos
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000925:Anticoagulants / Q000009:adverse effects*; D001120:Arginine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002985:Clinical Protocols; D000069604:Dabigatran / Q000009:adverse effects / Q000037:antagonists & inhibitors; D004638:Emergency Treatment; D015951:Factor Xa / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D006761:Hospitals; D006801:Humans; D018579:Patient Selection; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D011720:Pyrazoles / Q000009:adverse effects / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000009:adverse effects / Q000037:antagonists & inhibitors; D011728:Pyridones / Q000009:adverse effects / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069552:Rivaroxaban / Q000009:adverse effects / Q000037:antagonists & inhibitors; D013514:Surgical Procedures, Operative; D013844:Thiazoles / Q000009:adverse effects / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants; D065427:Factor Xa Inhibitors; C580915:PRT064445; D010879:Piperazines; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D011994:Recombinant Proteins; D013844:Thiazoles; C522181:apixaban; D001120:Arginine; C000594745:idarucizumab; D000069552:Rivaroxaban; D015951:Factor Xa; D000069604:Dabigatran; C552171:edoxaban; C000593571:PER977