What are the treatment guidelines for a patient with hematuria on Eliquis (apixaban) who continues to bleed after holding the medication for 3 days?

Management of Persistent Hematuria in a Patient on Apixaban After 3-Day Hold

For a patient with persistent hematuria after holding apixaban (Eliquis) for 3 days, administration of andexanet alfa is recommended if the bleeding is major, or administration of activated charcoal if the last dose was taken within 2-4 hours. 1, 2

Assessment of Bleeding Severity

• Determine if the bleeding is major by assessing for:
  • Hemodynamic instability (heart rate increase, systolic BP <90 mmHg, drop in systolic BP >40 mmHg) 1
  • Bleeding in a critical site (intracranial, intraocular, spinal, thoracic, pericardial, intra-abdominal, retroperitoneal, intra-articular) 1
  • Need for blood transfusion 1

Management Algorithm for Persistent Hematuria on Apixaban

For Major Bleeding:

1. Reversal agent administration:

   • Administer andexanet alfa (first-line for apixaban reversal) 1
     • Low dose: 400 mg IV bolus followed by 4 mg/min infusion for up to 120 minutes if last dose was ≥8 hours ago or was ≤5 mg taken <8 hours ago
     • High dose: 800 mg IV bolus followed by 8 mg/min infusion for up to 120 minutes if last dose was >5 mg taken <8 hours ago 1
   • If andexanet alfa is unavailable, administer prothrombin complex concentrate (PCC) or activated PCC 1

2. Supportive measures:

   • Provide local therapy/manual compression 1
   • Volume resuscitation 1
   • Consider activated charcoal if last dose was taken within 2-4 hours 1, 2
   • Assess for and manage comorbidities that could contribute to bleeding (thrombocytopenia, uremia, liver disease) 1

3. Surgical/procedural management:

   • Consider surgical/procedural management of bleeding site if appropriate 1

For Non-Major Bleeding:

1. Continue holding apixaban for at least 48 hours or until adequate hemostasis is achieved 2

2. Supportive measures:

   • Provide local therapy/manual compression 1
   • Consider activated charcoal if last dose was taken within 2-4 hours 1, 2

3. Investigate underlying cause:

   • Urological evaluation is recommended as hematuria in patients on anticoagulants often indicates significant genitourinary pathology 1, 3
   • Studies have shown 7-25% of patients with anticoagulant-associated hematuria have underlying neoplastic disease 4, 5, 3

Monitoring and Follow-up

• Monitor hemoglobin, hematocrit, and renal function 1
• Consider measuring anti-Factor Xa activity if available to assess residual apixaban effect 1
• Assess renal function as acute kidney injury can be aggravated by apixaban (anticoagulant-related nephropathy) 6

Restarting Anticoagulation

• Restart apixaban only after adequate hemostasis has been established 2
• For patients with high thrombotic risk, consider bridging with parenteral anticoagulation (UFH or LMWH) if prolonged apixaban interruption is necessary 1
• Reassess the appropriate dose of apixaban when restarting based on patient characteristics (age, weight, renal function) 2

Important Considerations

• Apixaban has a half-life of approximately 12 hours, so after 3 days (72 hours), drug levels should be minimal in patients with normal renal function 2

• Persistent bleeding after this period suggests either:

  1. Impaired drug clearance (e.g., renal dysfunction)
  2. An underlying pathological cause of bleeding
  3. Severe coagulopathy requiring reversal intervention 1

• A thorough urological evaluation is warranted in patients with persistent hematuria even when on anticoagulants, as studies show 30% have significant urinary tract disease 3