title: Pharmacologic interventions for reversing the effects of oral anticoagulants.
abstract: OBJECTIVE
  To describe the pharmacologic agents and strategies used for urgent reversal of warfarin and the target-specific oral anticoagulants dabigatran, rivaroxaban, and apixaban.
  
  
  CONCLUSIONS
  To reverse the anticoagulant effects of warfarin in patients who are bleeding or need surgery, exogenous vitamin K (phytonadione) may be used in combination with another, shorter-acting intervention, such as fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), recombinant factor VIIa, or activated PCC (aPCC). Three-factor PCC contains factors II, IX, and X in an inactivated form, and four-factor PCC also includes factor VII in an inactivated form. No four-factor PCC products are available in the United States, but aPCC, which contains the same four factors with factor VII provided in an activated form, is available. The intervention depends on the International Normalized Ratio, presence of bleeding, and need for and timing of surgery. Research suggests that clotting factor concentrates are more effective than FFP alone for warfarin reversal. These products also may be useful for reversing the effects of target-specific oral anticoagulants, but limited efficacy and safety data are available to support their use. The risks and benefits associated with these products need to be weighed before their use for reversal of dabigatran, rivaroxaban, or apixaban. Additional clinical data are needed to clearly define the role of concentrated clotting factor products in reversal and to determine the optimal clotting factor concentrate product and dose for urgent reversal of oral anticoagulation.
  
  
  CONCLUSIONS
  Phytonadione and clotting factor concentrates appear to have a role for reversal of warfarin, and limited evidence suggests that clotting factor concentrates could have a role in reversal of target-specific oral anticoagulants in an emergency situation.
authors: Department of Pharmacy Services, Henry Ford Hospital, Detroit, MI 48202, USA. jkalus1@hfhs.org
authors: James S
authors: JS
authors: Kalus
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D000991:Antithrombins / Q000009:adverse effects / Q000037:antagonists & inhibitors; D001562:Benzimidazoles / Q000009:adverse effects / Q000037:antagonists & inhibitors; D001779:Blood Coagulation Factors / Q000008:administration & dosage*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D000069604:Dabigatran; D004359:Drug Therapy, Combination; D004630:Emergencies; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D019934:International Normalized Ratio; D009025:Morpholines / Q000009:adverse effects / Q000037:antagonists & inhibitors; D010949:Plasma; D011720:Pyrazoles / Q000009:adverse effects / Q000037:antagonists & inhibitors; D011728:Pyridones / Q000009:adverse effects / Q000037:antagonists & inhibitors; D000069552:Rivaroxaban; D013514:Surgical Procedures, Operative / Q000009:adverse effects; D013876:Thiophenes / Q000009:adverse effects / Q000037:antagonists & inhibitors; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome; D010837:Vitamin K 1 / Q000008:administration & dosage*; D014859:Warfarin / Q000009:adverse effects / Q000037:antagonists & inhibitors; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D000991:Antithrombins; D001562:Benzimidazoles; D001779:Blood Coagulation Factors; D009025:Morpholines; D011720:Pyrazoles; D011728:Pyridones; D013876:Thiophenes; D015091:beta-Alanine; C025667:prothrombin complex concentrates; C522181:apixaban; D014859:Warfarin; D010837:Vitamin K 1; D000069552:Rivaroxaban; D000069604:Dabigatran