How should a patient on apixaban with a massive upper gastrointestinal bleed be managed?

Management of Massive Upper GI Bleeding in Patients on Apixaban

Immediately discontinue apixaban and proceed directly to endoscopy without delay—do not wait for anticoagulation reversal or normalization of coagulation parameters. 1

Immediate Anticoagulation Management

Withhold apixaban at presentation. For most patients with massive upper GI bleeding, supportive care alone is sufficient as apixaban has a half-life of approximately 12 hours and will clear within 24 hours in patients with normal renal function. 1, 2

Reversal Agent Indications

Administer andexanet alfa only for life-threatening hemorrhage (hemodynamic instability requiring vasopressors, hemoglobin drop ≥2 g/dL, transfusion requirement ≥2 units RBCs, or critical site bleeding). 1, 2

• Low-dose regimen: 400 mg IV bolus followed by 4 mg/min infusion for 120 minutes if the last apixaban dose was ≤5 mg and taken <8 hours prior 1, 2
• High-dose regimen: 800 mg IV bolus followed by 8 mg/min infusion for 120 minutes if the last apixaban dose was >5 mg and taken <8 hours prior 1, 2

If andexanet alfa is unavailable, administer four-factor prothrombin complex concentrate (4F-PCC) as the alternative, which achieves effective hemostasis in 72.4% of patients with major bleeding on apixaban. 1, 2, 3

Critical Pitfall

Do not use standard coagulation tests (PT, aPTT, INR) to guide management—these are unreliable for apixaban and should not influence clinical decisions. 2

Endoscopy Timing and Approach

Perform endoscopy within 24 hours without delaying for anticoagulation reversal. The 2019 International Consensus Group provides a strong recommendation that endoscopy should not be delayed in patients receiving DOACs, even without reversal. 1

• Proceed with endoscopic hemostatic therapy as indicated by endoscopic findings 1
• For high-risk stigmata (active bleeding or visible vessel), use thermocoagulation, sclerosant injection, or through-the-scope clips 1
• Epinephrine injection alone is insufficient and must be combined with another method 1

Transfusion Strategy

Use restrictive transfusion thresholds:

• Without cardiovascular disease: Transfuse at hemoglobin <80 g/L 1
• With cardiovascular disease: Transfuse at a higher threshold than those without cardiovascular disease 1

This approach balances the risk of anemia against transfusion-related complications. 1

Concomitant Antiplatelet Management

If the patient is on aspirin for secondary cardiovascular prevention, continue it during the acute bleeding episode. The mortality benefit of continuing aspirin (1.3% vs 12.9% at 8 weeks) far outweighs the increased rebleeding risk. 1

If on dual antiplatelet therapy (aspirin + P2Y12 inhibitor), continue aspirin and withhold the P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel). 1

• Resume the P2Y12 inhibitor within 5 days maximum due to high thrombosis risk after this timeframe 1
• Consult cardiology before discontinuing antiplatelet therapy, particularly in patients with acute coronary syndrome within 6 months 1

Restarting Apixaban

Resume apixaban at a maximum of 7 days after hemorrhage in patients with ongoing anticoagulation indication once hemostasis is confirmed. 1, 2, 4

For high thrombotic risk patients (recent stroke, mechanical heart valve, recent VTE), consider restarting within 3 days after achieving hemostasis. 4

Delay or permanently discontinue anticoagulation if:

• Bleeding occurred at a critical site 2
• Patient is at high risk of rebleeding 2
• Source of bleeding has not been identified 2
• Surgical or invasive procedures are planned 2

Key Consideration

Apixaban has rapid onset of action with full anticoagulant activity within 3 hours of the first dose, so timing of resumption must account for confirmed hemostasis and low rebleeding risk. 1

Supportive Measures

Consider activated charcoal if apixaban was ingested within 2-4 hours, as it reduces absorption by 50% at 2 hours and 27% at 6 hours. 1, 2, 5

Administer proton pump inhibitor therapy to downstage endoscopic lesions, though this should not delay endoscopy. 1

Avoid platelet transfusions—they do not reduce rebleeding and are associated with higher mortality in patients on antiplatelet agents. 1

Institutional Coordination

Ensure multidisciplinary management with access to an endoscopist trained in endoscopic hemostasis available on an urgent basis. 1

Liaise with cardiology for patients with mechanical heart valves, recent coronary stents, or high thrombotic risk conditions to balance bleeding and thrombotic risks. 1, 4