What is the management for a patient on anticoagulation (blood thinner) therapy, such as warfarin or novel oral anticoagulants (NOACs) like apixaban (eliquis) or rivaroxaban (xarelto), presenting with hematuria (blood in the urine)?

Management of Hematuria in Patients on Anticoagulation

Stop the anticoagulant immediately and assess bleeding severity to determine if this is a major bleed requiring reversal agents, while simultaneously investigating for underlying urologic pathology since 25% of anticoagulated patients with gross hematuria harbor malignancy. 1

Initial Assessment and Severity Classification

Determine if the bleeding is major by assessing for any of the following criteria 1:

• Hemodynamic instability (hypotension, tachycardia)
• Hemoglobin decrease ≥2 g/dL
• Requirement for ≥2 units of red blood cell transfusion
• Bleeding at a critical site (though isolated hematuria without clot obstruction typically does not qualify as critical site bleeding)

Immediate Management Based on Severity

For Major Bleeding (Hemodynamically Unstable or Severe Hematuria)

Stop the anticoagulant and all antiplatelet agents immediately 1, 2

Provide supportive care including 1:

• Volume resuscitation with crystalloids
• Local measures (bladder irrigation if clots present)
• Assess and manage comorbidities contributing to bleeding (thrombocytopenia, uremia, liver disease)

For warfarin: Administer vitamin K 5-10 mg by slow IV injection PLUS four-factor prothrombin complex concentrate (PCC) for rapid reversal 1

For rivaroxaban or apixaban: Consider andexanet alfa for life-threatening bleeding; if unavailable, use four-factor PCC at 50 U/kg (maximum 4,000 units) 1, 2, 3

For dabigatran: Administer idarucizumab if available; if unavailable, use PCC or activated PCC at 50 U/kg 1

For Non-Major Bleeding (Hemodynamically Stable, Mild-Moderate Hematuria)

Stop the anticoagulant temporarily 1, 4

Do NOT administer reversal agents for non-major bleeding in patients on DOACs 1

For warfarin with non-major bleeding: Consider vitamin K 2-5 mg PO or IV (lower dose than major bleeding) 1

Provide local therapy such as bladder irrigation if clots are present 1

Continue supportive care and monitor hemoglobin 1

Critical Pitfall: Mandatory Investigation for Malignancy

Do NOT attribute hematuria solely to anticoagulation—always investigate for underlying pathology because 1:

• 25% of patients with gross hematuria on anticoagulants have urologic tumors 1
• The incidence of hematuria in anticoagulated patients (3.2%) is similar to non-anticoagulated patients (4.8%), suggesting anticoagulation unmasks rather than causes bleeding 1
• Significant pathology (cancer, stones, infection) is found in approximately 60% of cases 5

Perform complete urologic evaluation including 1, 6:

• Cystoscopy
• Upper tract imaging (CT urography or renal ultrasound with excretory urography)
• Urine cytology

Do not delay investigation even if coagulation parameters are supratherapeutic—excessive anticoagulation should not impede full evaluation 6

Transfusion Strategy

Use restrictive transfusion thresholds 2:

• Hemoglobin trigger of 70 g/L with target 70-90 g/L for most patients
• Higher threshold (Hb trigger 80 g/L, target 100 g/L) for patients with cardiovascular disease

Duration of Anticoagulant Hold

For mild-moderate hematuria: Holding anticoagulation for less than 2 days typically achieves hemostasis 4

Antiplatelet therapy can often be continued during mild hematuria episodes without increasing rebleeding risk 4

Restarting Anticoagulation

Once bleeding is controlled, assess whether to restart anticoagulation by evaluating 1:

Delay or discontinue anticoagulation if 1:

• Source of bleeding not yet identified
• High risk of rebleeding or death/disability with rebleeding
• Surgical/procedural intervention planned
• Patient preference against restarting

Restart anticoagulation if 1, 2:

• Bleeding controlled
• Strong indication for anticoagulation exists (e.g., atrial fibrillation with CHA₂DS₂-VASc ≥2, recent VTE)
• Source identified and treated

Timing: Consider restarting within 7 days for high thrombotic risk patients once hemostasis achieved 2, 7

Agent selection for restart: Consider switching from warfarin or heparin to low-molecular-weight heparin or DOACs to potentially reduce recurrence risk 4

Special Considerations

Warfarin-related nephropathy: Rarely, warfarin can cause acute kidney injury through glomerular hemorrhage and tubular obstruction by red blood cell casts, particularly in patients with chronic kidney disease 8

Medication-specific risk: Rivaroxaban and warfarin carry higher hematuria risk compared to apixaban, which appears safer in pharmacovigilance data 9

Avoid unnecessary interventions: Do not remove urinary catheters or restrict mobility specifically to prevent rebleeding, as these measures are ineffective 4