title: Reversal of the novel oral anticoagulants dabigatran, rivoraxaban, and apixaban.
abstract: OBJECTIVE
  We summarize the available data related to reversing the anticoagulant effect of the oral direct thrombin and factor Xa inhibitors and provide our opinion on treating patients presenting with severe and life-threatening hemorrhage related to these agents.
  
  
  RESULTS
  No specific antidotes are currently available for the oral direct thrombin and factor Xa inhibitors but two promising agents are under investigation in phase 3 trials. No data are available on reversing these agents in bleeding patients. Activated charcoal may be effective in reducing factor Xa inhibitor absorption up to 6 h after ingestion. Animal models suggest that unactivated 4-factor prothrombin complex concentrate may be an effective reversal agent. Recent data in warfarin-treated patients suggest that 4-factor prothrombin complex concentrate may provide more rapid and effective hemostasis than fresh frozen plasma.
  
  
  CONCLUSIONS
  In the absence of evidence in bleeding patients, animal models and ex-vivo studies suggest administration of coagulant factors in the form of hemostatic agents may be of benefit in reversing the effect of direct thrombin and factor Xa inhibitors. Specific reversal agents and clinical data in patients with hemorrhage remain an unmet need.
authors.affiliation: aDepartment of Neurology bDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Liotta
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Levasseur-Franklin
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Naidech
mesh_terms: D000818:Animals; D000931:Antidotes / Q000627:therapeutic use; D000991:Antithrombins / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D003029:Coagulants / Q000627:therapeutic use*; D000069604:Dabigatran; D065427:Factor Xa Inhibitors / Q000627:therapeutic use; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006470:Hemorrhage / Q000628:therapy; D006801:Humans; D023421:Models, Animal; D009025:Morpholines / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*; D000069552:Rivaroxaban; D013876:Thiophenes / Q000627:therapeutic use*; D013923:Thromboembolism / Q000188:drug therapy; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000931:Antidotes; D000991:Antithrombins; D001562:Benzimidazoles; D003029:Coagulants; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D009025:Morpholines; D011720:Pyrazoles; D011728:Pyridones; D013876:Thiophenes; D015091:beta-Alanine; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran