How should I manage visible hematuria in a patient taking apixaban (Eliquis)?

Management of Visible Hematuria in Patients on Apixaban

For visible hematuria on apixaban, immediately stop the anticoagulant, provide local therapy and supportive care, and do NOT administer reversal agents unless the bleeding meets criteria for major bleeding (hemodynamic instability, hemoglobin drop ≥2 g/dL, or transfusion requirement ≥2 units). 1

Initial Assessment: Classify Bleeding Severity

Determine if the hematuria qualifies as major bleeding by checking for ANY of these criteria: 1

• Hemodynamic instability (hypotension, tachycardia requiring intervention)
• Hemoglobin decrease ≥2 g/dL from baseline
• Transfusion requirement ≥2 units of red blood cells
• Bleeding at a critical site (though isolated hematuria typically does not qualify unless associated with urinary tract obstruction or renal pelvis involvement)

If NONE of these criteria are met, the hematuria is classified as non-major bleeding. 1

Management Algorithm for Non-Major Hematuria (Most Common Scenario)

Immediate Actions:

• Stop apixaban immediately 1
• Provide local therapy: bladder irrigation if clots present, continuous bladder irrigation for persistent bleeding 1
• Manual compression is not applicable, but ensure adequate hydration to maintain urine flow 1
• Provide supportive care and volume resuscitation with IV fluids 1

What NOT to Do:

• Do NOT administer reversal agents (andexanet alfa) or hemostatic agents (prothrombin complex concentrate) for non-major bleeding 1
• Do NOT give vitamin K (apixaban is not a vitamin K antagonist) 1

Antiplatelet Management:

• Consider stopping antiplatelet agents (aspirin, clopidogrel) if the patient is on concomitant therapy, as this significantly increases bleeding risk 1, 2

Assess Contributing Factors:

• Check for and manage comorbidities that worsen bleeding: 1
  • Thrombocytopenia (platelet count)
  • Uremia (renal function - apixaban half-life extends to 17 hours with severe renal impairment) 3
  • Liver disease (coagulation studies)

Verify Appropriate Dosing:

• Confirm the patient was on the correct apixaban dose - underdosing paradoxically increases thrombotic risk, while overdosing increases bleeding 3
• Common dosing errors include failure to adjust for changing renal function or body weight 3

Management Algorithm for Major Hematuria (Less Common)

If the hematuria meets major bleeding criteria: 1

Immediate Actions:

• Stop apixaban AND all antiplatelet agents 1
• Provide aggressive supportive care: volume resuscitation, blood transfusion as needed 1
• Apply local therapy: continuous bladder irrigation, consider cystoscopy for clot evacuation 1
• Assess for surgical/procedural management of the bleeding source 1

Reversal Agent Consideration:

• Administer andexanet alfa if bleeding is life-threatening or uncontrolled despite supportive measures 1, 4
• Alternative: If andexanet alfa unavailable, consider prothrombin complex concentrate (PCC) off-label 4
• Note: Apixaban has a relatively short half-life (6-15 hours with normal renal function), so supportive care alone may suffice if the drug was taken >12 hours prior 4, 3

Critical Next Step: Rule Out Urological Malignancy

Hematuria in anticoagulated patients requires full urological evaluation regardless of anticoagulation status. 5, 6

• Do NOT attribute hematuria solely to anticoagulation - up to 20-30% of patients have underlying urological pathology including malignancy 5
• Timing: Arrange cystoscopy, upper tract imaging (CT urography or renal ultrasound with IVP), and urine cytology once bleeding is controlled 5
• Hematuria typically occurs within the first 72 hours of anticoagulation initiation if drug-related, but later onset suggests structural pathology 6

When to Restart Apixaban

Delay restarting anticoagulation if ANY of the following apply: 1

• Source of bleeding has not been identified or definitively treated
• Patient is at high risk of rebleeding (e.g., bladder tumor requiring resection)
• Surgical or invasive urological procedures are planned
• Patient does not wish to restart at this time

Restart apixaban if: 1

• Bleeding is controlled (typically within 24-48 hours for non-major hematuria) 6
• Source has been identified and treated
• Patient has high thrombotic risk (e.g., atrial fibrillation with CHA₂DS₂-VASc ≥2, recent VTE)
• Timing: Generally 24 hours after bleeding control for low-risk scenarios, 48-72 hours for higher-risk situations 7

Alternative Anticoagulation Strategy:

• Consider switching to low molecular weight heparin (LMWH) rather than restarting apixaban if recurrent hematuria is a concern, as this may reduce rebleeding rates 6

Important Pitfalls to Avoid

• Do NOT continue apixaban during active visible hematuria - even mild hematuria warrants temporary cessation 1
• Do NOT skip urological workup - anticoagulation does not explain hematuria, it only unmasks underlying pathology 5
• Do NOT use reversal agents for non-major bleeding - this increases thrombotic risk without clear benefit 1
• Do NOT forget to check renal function - apixaban accumulates with renal impairment, prolonging bleeding risk 3, 8
• Apixaban appears safer than rivaroxaban or warfarin for hematuria risk based on pharmacovigilance data, but still requires the same management approach 9