What to do if a patient on Eliquis (apixaban) experiences hematuria?

Management of Hematuria in Patients on Eliquis (Apixaban)

Evaluate hematuria in patients on apixaban thoroughly for underlying urologic pathology regardless of anticoagulation status, as bleeding on anticoagulants does not exclude malignancy and requires full urologic workup. 1

Immediate Assessment and Bleeding Severity Classification

• Determine if the hematuria represents major bleeding by assessing for: hemodynamic instability, bleeding at a critical site, hemoglobin drop ≥2 g/dL, or need for ≥2 units of blood transfusion 2

• For gross (visible) hematuria, temporarily discontinue apixaban immediately and provide supportive care while assessing bleeding severity 2

• Monitor hemoglobin, hematocrit, and renal function closely 3

• Measure anti-Factor Xa activity if available to assess residual apixaban effect 3

Management Based on Bleeding Severity

For Major or Life-Threatening Bleeding:

• Stop apixaban immediately and provide local therapy/manual compression if applicable 2

• Provide volume resuscitation and supportive care 2, 3

• Consider reversal agents for life-threatening bleeding: andexanet alfa (specific reversal agent for apixaban) or prothrombin complex concentrates (PCCs) 2, 4

• Andexanet alfa dosing: Low dose (400 mg IV bolus followed by 4 mg/min infusion for up to 120 minutes) if last apixaban dose was ≥8 hours ago or ≤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 3

• If andexanet alfa unavailable, administer PCC or activated PCC 3, 4

• Consider surgical/procedural management of the bleeding source 2, 3

For Mild to Moderate Hematuria:

• Hold apixaban temporarily (typically for less than 2 days for most cases) 5

• Provide supportive care including hydration and bladder irrigation if needed 5, 6

• The pharmacodynamic effect of apixaban persists for at least 24 hours after the last dose (approximately two drug half-lives) 4

Critical Urologic Evaluation

All patients with gross hematuria require complete urologic evaluation regardless of anticoagulation status, as anticoagulants do not cause hematuria but rather unmask underlying pathology. 1

• Refer for urgent urologic evaluation for all adults with gross hematuria, even if self-limited, given the >10% risk of underlying malignancy 1

• Complete urologic workup includes: upper tract imaging (CT urography preferred) and cystoscopy 1

• For microscopic hematuria (≥3 RBCs per high-power field on microscopic examination), confirm with repeat urinalysis and consider urology referral for cystoscopy and imaging in the absence of demonstrable benign cause 1

• Evaluate for glomerular versus non-glomerular source: presence of dysmorphic RBCs, RBC casts, or significant proteinuria suggests glomerular disease requiring nephrology evaluation 1, 7

Restarting Anticoagulation

Before restarting apixaban, ensure the bleeding source has been identified and addressed, assess rebleeding risk, and confirm continued indication for anticoagulation. 2

• Once bleeding is controlled and patient is stable, apixaban can be resumed at least 6 hours after bleeding control (some sources suggest 5 hours after catheter removal in neuraxial procedures) 2, 4

• For patients with high thrombotic risk requiring prolonged apixaban interruption, consider bridging with parenteral anticoagulation (unfractionated heparin or low molecular weight heparin) 3

• Re-establishing anticoagulation with low molecular weight heparin or non-vitamin K dependent oral agents may reduce recurrence risk compared to continuing warfarin 5

• Consider alternative anticoagulation options if apixaban is contraindicated due to the bleeding event 2

Important Clinical Pitfalls

• Do not assume anticoagulation is the sole cause of hematuria - anticoagulants unmask underlying pathology rather than causing de novo bleeding 1, 6

• Hematuria is more common in the first 72 hours of anticoagulant therapy and is dose-dependent 5

• Persistent hematuria after holding apixaban for 3 days suggests: impaired drug clearance, underlying pathological bleeding source, or severe coagulopathy requiring reversal intervention 3

• Be aware of anticoagulant-related nephropathy (ARN): apixaban can aggravate pre-existing acute kidney injury through glomerular hemorrhage and red blood cell cast formation 8

• Drug-drug interactions occur in approximately 32% of anticoagulated patients and may influence bleeding severity - systematically review all medications 6

• Monitoring PT, INR, aPTT, or anti-Factor Xa activity is not useful for guiding PCC administration and is not recommended 4

• Hemodialysis does not substantially impact apixaban exposure 4

• Protamine sulfate and vitamin K are not effective for reversing apixaban 4