Rivaroxaban reversal

Background

  • 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

Evaluation

  • 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)

Management

  • 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 (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 (Savaysa®) 10-14 hrs (longer in renal impairment) ~ 25% As above
Rivaroxaban (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

^Off-label

Andexanet alfa

FDA approved in May 2018, limited availability June 2018

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

Disposition

  • admission to a monitored setting

See Also

External Links

References

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