What medications can cause gross hematuria?

Medications That Can Cause Gross Hematuria

Anticoagulants and antiplatelet drugs are the most common medications that cause gross hematuria, with rivaroxaban and warfarin being the most frequently associated agents. 1

Anticoagulants

Anticoagulants are strongly associated with gross hematuria, with different risk profiles among various agents:

• Warfarin: Significantly increases risk of bleeding when GFR <30 ml/min/1.73 m², requiring lower doses and close monitoring 2. Associated with higher rates of hematuria compared to other anticoagulants 1.

• Direct Oral Anticoagulants (DOACs):

  • Rivaroxaban: Highest association with hematuria among DOACs 1
  • Dabigatran: Associated with 2.5% of fatal hematuria episodes 1
  • Apixaban: Appears to be the safest DOAC in terms of hematuria risk 1

• Injectable Anticoagulants:

  • Enoxaparin (LMWH): Associated with 3% of fatal hematuria episodes 1
  • Heparin: Requires dose reduction when GFR <30 ml/min/1.73 m² 2

Antiplatelet Agents

Antiplatelet medications significantly increase hematuria risk, particularly when combined with anticoagulants:

• Aspirin: Common cause of hematuria, particularly associated with hemorrhagic cystitis 3
• Clopidogrel: Frequently associated with hematuria reports 1
• NSAIDs: Increase bleeding risk through platelet function inhibition 2
  • Ibuprofen: Commonly associated with hematuria 1

The combination of anticoagulants with antiplatelet agents dramatically increases hematuria risk (10.48 times higher than in unexposed patients) 4.

Chemotherapeutic Agents

• Cyclophosphamide: Associated with 7.2% of fatal hematuria episodes, the highest among commonly prescribed medications 1. Can cause hemorrhagic cystitis, bladder necrosis, and ulcerative cystitis 5.

Other Medications

• Lansoprazole: Associated with hematuria reports 1
• Penicillins: In high doses can increase risk of bleeding with warfarin 2
• Cephalosporins: Second and third-generation cephalosporins augment anticoagulant effect of warfarin 2

Clinical Implications and Management

1. Severity Assessment:

   • Gross hematuria associated with anticoagulants has a high association with malignancy (up to 30-40%) 2
   • Approximately 25% of patients with anticoagulant-associated hematuria are found to have urinary tract tumors 3

2. Medication Management:

   • For moderate to severe hematuria: Temporarily suspend anticoagulation
   • For mild hematuria: May continue anticoagulation with careful monitoring 6
   • When restarting anticoagulation after hematuria control, consider switching from warfarin to DOACs (preferably apixaban) or LMWH 6

3. Diagnostic Approach:

   • Full urologic evaluation is warranted even in patients with excessive anticoagulation 3
   • Evaluation should include cystoscopy and either excretory urography or ultrasound 3

Risk Factors for Anticoagulant-Associated Hematuria

• Advanced age (>65 years)
• Renal impairment (particularly GFR <30 ml/min/1.73 m²)
• Concomitant use of multiple antithrombotic agents
• Higher doses of anticoagulants 6
• First 72 hours of therapy initiation 6

Prevention

• Use the lowest effective dose of anticoagulants in high-risk patients
• Consider apixaban over rivaroxaban or warfarin in patients at increased risk of hematuria 1
• Avoid combination of anticoagulants with antiplatelet agents when possible 4
• Ensure adequate hydration in patients on cyclophosphamide to reduce risk of hemorrhagic cystitis 5

Patients receiving anticoagulants or antiplatelet medications should be informed about the risk of hematuria and advised to seek prompt medical attention if it occurs.