What to do in a case of upper GI (Gastrointestinal) bleeding in a patient with atrial fibrillation taking Apixaban (apixaban)?

Management of Upper GI Bleeding in a Patient with Atrial Fibrillation Taking Apixaban

In a patient with atrial fibrillation experiencing upper GI bleeding while on apixaban, immediately interrupt apixaban therapy and consider andexanet alfa for life-threatening hemorrhage, with plans to restart anticoagulation within 7 days after hemostasis is achieved.1

Initial Management of Acute Upper GI Bleeding

• Discontinue apixaban immediately upon presentation with upper GI bleeding 1
• Provide fluid resuscitation if the patient is hemodynamically unstable 1
• Perform risk stratification to assess severity of bleeding 1
• Initiate transfusion support with a hemoglobin threshold of 70 g/L (aiming for 70-100 g/L) for most patients; consider a higher threshold for patients with cardiovascular disease 1
• Arrange for timely endoscopy to identify and treat the bleeding source 1, 2
• Consider pharmacological therapies such as terlipressin for suspected variceal bleeding 1

Reversal of Anticoagulation

• For life-threatening hemorrhage, consider andexanet alfa, a specific reversal agent for factor Xa inhibitors including apixaban 1, 3
• Prothrombin complex concentrates (PCCs) may be considered when specific reversal agents are not available 1, 3
• Note that vitamin K, fresh frozen plasma (FFP), or protamine sulfate are ineffective for reversing apixaban 1
• Activated charcoal may be useful if apixaban was recently ingested (within 2-4 hours) to reduce absorption 3
• Hemodialysis does not substantially impact apixaban exposure and is not recommended 3

Timing of Anticoagulation Resumption

• Restart apixaban within a maximum of 7 days after achieving hemostasis 1
• For apixaban specifically, optimal resumption is around 32 days after the index bleeding event, with a window of 21-47 days producing >99.9% of peak utility 4
• Consider the balance of risks: early resumption increases rebleeding risk while delayed resumption increases thromboembolic risk 4
• For patients at high risk of rebleeding, consider switching to warfarin instead of apixaban as it allows for more effective and rapid reversal if rebleeding occurs 1

Special Considerations

• Consult with the clinician who initiated anticoagulation therapy when making decisions about interruption and resumption 1
• For patients with high thromboembolic risk (recent stroke), consider earlier resumption of anticoagulation 1
• For patients with high bleeding risk, consider the following anticoagulation options:
  • Apixaban may be preferable to other DOACs as it is not associated with increased GI bleeding compared to warfarin 1, 5
  • Dabigatran 110 mg (where available) may also be considered for patients with prior GI bleeding 1

Monitoring and Follow-up

• No reliable bedside tests are available to accurately assess the anticoagulatory effect of apixaban 6
• Anti-factor Xa activity test can rule out apixaban effects if results are normal 6
• Normal values of global coagulation tests (PTT, PT) 4+ hours after apixaban intake generally indicate low drug levels 6
• Monitor for signs of recurrent bleeding after resumption of anticoagulation 2

Prevention of Future Bleeding Events

• Avoid medications with GI toxicity that may increase bleeding risk (NSAIDs, certain antiplatelet agents) 3, 2
• Consider dose reduction of apixaban (2.5 mg twice daily) in patients ≥80 years, ≤60 kg, or with serum creatinine ≥1.5 mg/dL 3
• Be aware of drug interactions affecting CYP3A4 or P-glycoprotein pathways that can alter apixaban levels 7, 3