What is the appropriate evaluation and treatment for hematuria (presence of blood in the urine)?

Evaluation and Management of Hematuria

Immediate Action Based on Presentation

All patients with gross hematuria require urgent urologic referral for cystoscopy and imaging, regardless of whether the bleeding is self-limited or the patient is on anticoagulation. 1, 2

Confirmation of True Hematuria

Before initiating any workup, confirm hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field rather than relying on dipstick alone, as dipstick specificity is only 65-99%. 1, 2, 3

• Dipstick-positive results must always be verified microscopically before proceeding with further evaluation. 1, 3
• For high-risk patients (defined below), a single urinalysis with ≥3 RBC/HPF may warrant full evaluation without waiting for repeat testing. 3

Exclude Benign Transient Causes

Before pursuing extensive workup, systematically exclude:

• Menstruation, vigorous exercise, sexual activity, trauma, viral illness 2, 4
• Urinary tract infection: Obtain urine culture if suspected; if positive, treat and repeat urinalysis 6 weeks after treatment to confirm resolution 4
• Medications (particularly analgesics) 2, 4
• Repeat urinalysis 48 hours after cessation of the suspected benign cause 4

Determine Glomerular vs. Non-Glomerular Source

Examine urinary sediment and perform targeted laboratory testing:

• Glomerular indicators (requiring nephrology referral):
  • Dysmorphic RBCs >80% 2, 4
  • Red cell casts 2, 4
  • Significant proteinuria >500 mg/24 hours 2, 4
  • Elevated serum creatinine 2, 4
• Non-glomerular indicators (requiring urologic evaluation):
  • Normal-appearing RBCs without casts 3
  • Absence of significant proteinuria 3

Risk Stratification for Urologic Malignancy

High-risk patients require complete urologic evaluation regardless of degree of hematuria:

• Age ≥40 years (some guidelines use ≥60 years as highest risk) 2, 4, 3
• Smoking history (risk increases with pack-years) 2, 4, 3
• Male sex 3
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 2, 4
• History of pelvic irradiation 2, 4
• Irritative voiding symptoms 2, 4
• History of gross hematuria 2, 4
• Analgesic abuse 2, 4

Critical caveat: The risk of malignancy with gross hematuria exceeds 10%, making prompt evaluation essential for mortality reduction. 5 Antiplatelet or anticoagulant therapy should never be used as an excuse to defer evaluation. 1, 2

Complete Urologic Evaluation for High-Risk or Unexplained Hematuria

For patients with non-glomerular hematuria without benign cause, or any high-risk features:

• CT urography is the preferred imaging modality for comprehensive upper tract evaluation (identifies hydronephrosis, calculi, renal/ureteral lesions) 2, 3
• Cystoscopy is mandatory in all patients ≥40 years and in younger patients with risk factors 2, 3
• Urine cytology should be obtained in patients with risk factors for transitional cell carcinoma or irritative voiding symptoms 2, 3
• Do NOT obtain urinary cytology or urine-based molecular markers in the initial evaluation of low-risk patients 1

Important consideration: Younger patients have the lowest pretest probability of malignancy but face the greatest lifetime carcinogenesis risk from CT radiation exposure, warranting careful risk-benefit assessment. 1

Follow-Up Protocol for Persistent Hematuria After Negative Workup

• Repeat urinalysis at 6,12,24, and 36 months 2, 4
• Monitor blood pressure at each visit 2, 4
• Refer to nephrology if hematuria persists with development of:
  • Hypertension 2, 4
  • Proteinuria >500 mg/24 hours 2, 4
  • Evidence of glomerular bleeding (red cell casts, dysmorphic RBCs) 2, 4
• Refer back to urology if patient develops:
  • Gross hematuria 3
  • Significant increase in degree of microscopic hematuria 3
  • New urologic symptoms 3

Common Pitfalls to Avoid

• Never screen asymptomatic adults with urinalysis for cancer detection 1
• Never defer evaluation in patients on anticoagulation – hematuria in this setting still requires full workup 1, 2
• Never rely on dipstick alone – always confirm microscopically 1, 3
• Never skip asking about gross hematuria in routine review of systems, as it significantly increases cancer risk (odds ratio 7.2) but is often underreported 4
• Studies show that primary care physicians frequently fail to fully evaluate hematuria according to guidelines, with only 36% of men and 8% of women appropriately referred to urology 6