Rapid reversal of rivaroxaban and apixaban with andexanet alfa in life/limb threatening bleeding

Dose regime and administration in adults (≥ 18 years old) who have taken either drug in the last 48 hours:

• Andexanet alpha should be prepared by following the guidance on the Medusa IV monograph.
• Andexanet alfa must be given by infusion pump via an inline 0.2 or 0.22 micron low protein filter (Medex filters available in ED).

• No dose adjustment is required for elderly patients or patients with renal impairment

Monitoring for efficacy is clinical, supported by blood tests

2 citrate coagulation tubes should be sent (taxied to RIE and NOT to BGH lab - the anti Xa levels done on apixaban are different from the levels for LMWH monitoring) requesting PT, APTT, and fibrinogen along with a request for anti Xa levels, pre and 30 mins post- Andexanet alfa. A significant reduction in Xa is not always seen and this does not suggest a lack of clinical efficacy.

Contraindications

• Previous life-threatening reaction to Andexanet alfa
  
  
• Patients with GCS < 7
  
  
• Poor prognosis for other reasons (e.g. life expectancy < 1 month)
  
  
• Safety and efficacy not established in children < 18-year-old or in pregnancy
  
  
• Not for the reversal of any other anticoagulants
  
  
• Not to be used for reversal for routine surgery

Cautions

• Significant thrombotic risk, especially in pro-thrombotic patients. This should be considered

Management of bleeding which does not fulfil the licensed criteria (listed above in Definition of life/limb-threatening bleeding) should be individualised and the following treatments considered:

• Consider activated charcoal to reduce absorption of apixaban/rivaroxaban in the case of overdose, within 2 hours of ingestion
  
  
• Consider the severity and location of the haemorrhage.
  
  
• Consider the use of appropriate symptomatic treatment including mechanical compression for severe epistaxis, surgical haemostasis with bleeding control procedures, fluid replacement and haemodynamic support, blood products (packed red cells or fresh frozen plasma, depending on associated anaemia or coagulopathy) or platelets to control bleeding.
  
  
• If these interventions do not control bleeding, a specific pro-coagulant reversal agent such as PCC or recombinant factor VIIa (r-FVIIa) could be considered.

When clinically stable with adequate haemostasis, anticoagulation can be re-commenced at 24 hours. Clinical review of the risk: benefit of and the timing of re-starting anticoagulation should be carried out by the clinical team in charge of the patient with input from haematology colleagues.