Rivaroxaban reversal


  • Millions are prescribed rivaroxaban (Xarelto) for atrial fibrillation, cardiac stents, stroke prevention, DVT/PE and ACS prophylaxis
  • Benefits: supposedly easier to dose, less monitoring than older anticoagulants
  • Downside: uncertainty regarding best mechanism of reversal in case of catastrophic intracranial or GI bleed
  • Multiple studies done since introduction of direct thrombin inhibitor (DTI) dabigatran and Factor Xa inhibitors rivaroxaban and apixaban to determine testing for supratherapeutic levels and best means of reversal, however no good trials that assessing human subjects who are potentially supratherapeutic and symptomatic

Clinical Features

  • Patient taking rivaroxaban with a life-threatening bleeding event (GI, ICH, etc.)

Differential Diagnosis

  • Bleeding secondary to other coagulopathy
  • Spontaneous bleeding


  • CBC
  • aPTT/PT: Factor Xa inhibitors affect PT, however unlike with warfarin, degree of PT elevation not directly correlated to level of anticoagulation
  • non contrast head CT showing ICH
  • Antifactor Xa assays- measure drug levels but not degree of anticoagulation, need to be calibrated for rivaroxaban not LMWH, and often not available in a timely fashion
  • Evaluation of clinical manifestation of bleeding (e.g. head CT, endoscopy)


  • IV/O2/Monitor, ABCs
  • Standard resuscitation with IVF; PRBCs if needed
  • If ICH, treat for increased ICP
  • Currently published manuscripts and protocols is that either PCC or aPCC is recommended as a reversal agent for DTIs and FXa inhibitors, with no clear data as to which is superior.
  • Consider Tranexamic acid

Factor Xa Inhibitor Reversal

Anticoagulant Half-life Removed by HD Strategies to reverse or minimize anticoagulant effects
Apixaban[1] (Eliquis®) 8-15 hrs (longer in renal impairment) No
  • If ingested within 2 hours, administer activated charcoal
  • 4-factor PCC (Kcentra™)^
    • 25units/kg—max 2500 units for treatment of documented intracranial hemorrhage
    • 50 units/kg—max 5000 units for all other life-threatening bleeds
Edoxaban[2] (Savaysa®) 10-14 hrs (longer in renal impairment) ~ 25% As above
Rivaroxaban[3] (Xarelto®) 9-13 hrs (longer in renal impairment) No As above
Fondaparinux (Arixtra®) 17-21 hrs (significantly longer in renal impairment) No 4-factor PCC (Kcentra™)^ 50 units/kg—max 5000 units


Andexanet alfa

FDA approved in May 2018, limited availability June 2018

  • Cost is $20,000 to $55,000 per dose
  • Trial that led to FDA approval does not have the most sound evidence behind it [4]:
    • Prospective single center single group study of 352 patients receiving a Factor Xa Inhibitor (apixaban, rivaroxaban, edoxaban, enoxaparin) with life threatening bleed (those with expected survival <1 month were excluded).
    • Anti-Factor Xa activity was decreased in all groups. 82% were judged to have excellent hemostatic control. 14% mortality rate at 30 days.
    • No comparison group available. It is unlikely that following anti-Factor Xa activity as a lab value is clinically important. High mortality rate even after excluding sick patients.

Low Dose

400 mg IV bolus at rate of ~30 mg/minute, followed 2 minutes later by 4 mg/minute for up to 120 minutes

High Dose

800 mg IV bolus at rate of ~30 mg/minute, followed 2 minutes later by 8 mg/minute for up to 120 minutes


  • admission to a monitored setting

See Also

External Links


  1. Akwaa, F., & Spyropoulos, A. (2013). Treatment of Bleeding Complications When Using Oral Anticoagulants for Prevention of Strokes. Current Treatment Options In Cardiovascular Medicine, 15(3), 288-298. doi:10.1007/s11936-013-0238-5
  2. Awad, N., & Cocchio, C. (2013). Activated Prothrombin Complex Concentrates for the Reversal of Anticoagulant-Associated Coagulopathy. Pharmacy And Therapeutics, 38(11), 696.
  3. Babilonia, K., & Trujillo, T. (2014). The role of prothrombin complex concentrates in reversal of target specific anticoagulants. Thrombosis Journal, 12(1), 8. doi:10.1186/1477-9560-12-8
  4. Davis, P., Musunuru, H., Walsh, M., Mitra, R., Ploplis, V., & Castellino, F. (2012). The ex vivo reversibility of dabigatran-induced whole-blood coagulopathy as monitored by thromboelastography: Mechanistic implications for clinical medicine. Thromb Haemost, 108(3), 586-588. doi:10.1160/th12-04-0222
  5. Ebright, J., & Mousa, S. (2014). Oral Anticoagulants and Status of Antidotes for the Reversal of Bleeding Risk. Clinical And Applied Thrombosis/Hemostasis. doi:10.1177/1076029614545211
  6. Eerenberg, E., Kamphuisen, P., Sijpkens, M., Meijers, J., Buller, H., & Levi, M. (2011). Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate: A Randomized, Placebo-Controlled, Crossover Study in Healthy Subjects. Circulation, 124(14), 1573-1579. doi:10.1161/circulationaha.111.029017
  7. Fawole, A., Daw, H., & Crowther, M. (2013). Practical management of bleeding due to the anticoagulants dabigatran, rivaroxaban, and apixaban. Cleveland Clinic Journal Of Medicine, 80(7), 443-451. doi:10.3949/ccjm.80a.13025
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  1. Eliquis prescribing information. Princeton, NJ: Bristol Myers Squibb; December 2012.
  2. Savaysa prescribing information. Parsippany, NJ: Daiichi Sankyo, Inc.; November 2015.
  3. Xarelto prescribing information. Titusville, NJ: Janssen Pharmaceuticals, Inc.; December 2014.
  4. Connolly SJ, Crowther M, Eikelboom JW, et al. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2019