When can apixaban (Eliquis) be restarted in a clinically stable patient with hemoperitoneum, no active contrast extravasation on imaging, and stable hemoglobin for at least 24 hours?

When to Restart Apixaban After Stable Hemoperitoneum

Restart apixaban 48-72 hours after documented hemostasis in a clinically stable patient with hemoperitoneum, no active blush, and stable hemoglobin for at least 24 hours, provided there is no planned surgical intervention and the bleeding source has been identified. 1

Initial Management: Stop Anticoagulation

• Immediately discontinue apixaban when hemoperitoneum is diagnosed, as this represents major bleeding (bleeding at a critical site requiring intervention or transfusion). 1
• Hemoperitoneum qualifies as major bleeding regardless of hemodynamic stability, given its location in a critical anatomical space. 1
• Do not administer reversal agents (andexanet alfa) for stable hemoperitoneum without active bleeding, as supportive care is sufficient when the patient is hemodynamically stable. 1, 2

Criteria for Restarting Anticoagulation

Required Conditions (All Must Be Met):

• Clinical stability: No hemodynamic instability, no ongoing transfusion requirements. 1
• Hemostasis achieved: Stable hemoglobin for ≥24 hours with no evidence of ongoing bleeding. 1
• No active extravasation: Imaging confirms no active contrast blush. 1
• Bleeding source identified: The cause of hemoperitoneum has been determined (e.g., anticoagulation-related vessel rupture, resolved trauma). 1
• No planned procedures: No surgical or invasive interventions anticipated in the next 48-72 hours. 1

Contraindications to Restarting (Delay if Present):

• High rebleeding risk: Unresolved underlying pathology (e.g., hepatic tumor, vascular malformation). 1
• Unknown bleeding source: If the etiology remains unclear, delay restart until identified. 1
• Planned surgery: Any anticipated intervention requiring hemostasis should delay restart. 1, 3
• Patient refusal: After shared decision-making regarding thrombotic vs. bleeding risks. 1

Timing of Restart

The optimal timing is 48-72 hours post-hemostasis for high bleeding risk procedures/events, which hemoperitoneum represents. 1

• The 2020 ACC Expert Consensus recommends restarting anticoagulation once "adequate hemostasis has been established" and "concern for additional bleeding complications has resolved." 1
• The 2018 European Heart Rhythm Association guideline specifies 48-72 hours post-high-bleeding-risk events before resuming full-dose DOACs. 1
• The FDA label for apixaban states it "should be restarted after surgical or other procedures as soon as adequate hemostasis has been established." 3

Pharmacokinetic Considerations:

• Apixaban has a half-life of approximately 12 hours, meaning the drug is essentially cleared within 48-60 hours of the last dose. 4
• Renal function impacts clearance: 27% of apixaban is renally excreted, so patients with CrCl <50 mL/min may have prolonged clearance. 4
• No bridging anticoagulation is needed when restarting apixaban, as therapeutic effect occurs within 3-4 hours of administration. 3, 4

Restart Protocol

Step 1: Confirm Stability (24-48 Hours Post-Bleed)

• Repeat hemoglobin at 24 hours to confirm stability (no drop ≥2 g/dL). 1
• Consider repeat imaging if there is any clinical concern for rebleeding (new abdominal pain, hemodynamic changes). 1

Step 2: Assess Thrombotic Risk

High thrombotic risk (restart at 48 hours if stable):

• Mechanical heart valve 1, 5
• Recent VTE (<3 months) 5
• Atrial fibrillation with CHA₂DS₂-VASc ≥4 1
• History of stroke/TIA 1

Moderate thrombotic risk (restart at 72 hours if stable):

• Atrial fibrillation with CHA₂DS₂-VASc 2-3 1
• Remote VTE (>3 months) 5

Step 3: Resume Apixaban at Standard Dose

• Do not use reduced-dose lead-in: Resume at the patient's maintenance dose (5 mg twice daily or 2.5 mg twice daily if dose-reduction criteria met). 3
• The 10 mg twice daily lead-in regimen is only for initial VTE treatment, not for restarting after bleeding. 3, 6
• Patients with bleeding risk factors (age >80, CrCl <50, concomitant antiplatelet therapy) had higher bleeding rates with lead-in dosing after parenteral anticoagulation. 6

Common Pitfalls to Avoid

• Do not restart too early (<48 hours): Even with stable hemoglobin at 24 hours, the risk of rebleeding remains elevated in the first 48 hours. 1
• Do not use bridging anticoagulation: LMWH or UFH bridging is not indicated when restarting DOACs and increases bleeding risk. 1
• Do not ignore renal function: Patients with CrCl <30 mL/min may require dose adjustment or alternative anticoagulation. 3, 4
• Do not restart if imaging shows evolving pathology: Any new findings on repeat imaging (expanding hematoma, pseudoaneurysm) mandate further delay. 1

Special Considerations

If Anticoagulation Cannot Be Restarted:

• Consider left atrial appendage occlusion for atrial fibrillation patients with contraindication to long-term anticoagulation. 1
• Reassess risk-benefit at regular intervals (e.g., 1-3 months) as bleeding risk may decrease over time. 1

Concomitant Antiplatelet Therapy:

• Discontinue antiplatelet agents if possible during the acute bleeding period. 1
• Reassess need for dual therapy (anticoagulation + antiplatelet) given increased bleeding risk. 1
• If both are essential (e.g., recent coronary stent), consider delaying restart to 72 hours and using proton pump inhibitor for GI protection. 1