Hematuria: Diagnostic and Treatment Approach
Immediate Classification and Triage
All patients with gross (visible) hematuria require urgent urologic referral with cystoscopy and upper tract imaging, regardless of whether bleeding is self-limited, because gross hematuria carries a 30-40% risk of malignancy. 1, 2
For microscopic hematuria, confirm the diagnosis with microscopic urinalysis showing ≥3 red blood cells per high-power field on at least two of three properly collected clean-catch midstream specimens before initiating any workup—dipstick testing alone has only 65-99% specificity and produces false positives. 1, 2, 3
Initial Evaluation: Exclude Benign Transient Causes
Before pursuing extensive evaluation, exclude:
- Menstruation (repeat urinalysis after menses) 2
- Vigorous exercise (transient hematuria resolves within 48-72 hours) 2
- Recent sexual activity or trauma 3
- Active urinary tract infection (treat infection, then repeat urinalysis 6 weeks post-treatment to confirm resolution) 4
Critical caveat: Anticoagulation or antiplatelet therapy does NOT explain hematuria and should never defer evaluation—these medications may unmask underlying pathology requiring investigation. 1, 2
Distinguish Glomerular from Non-Glomerular Sources
Perform comprehensive urinalysis with sediment examination to determine the source:
Glomerular hematuria indicators:
- >80% dysmorphic red blood cells on phase-contrast microscopy 2, 3
- Red blood cell casts (pathognomonic for glomerular disease) 2
- Tea-colored or cola-colored urine 2
- Significant proteinuria (protein-to-creatinine ratio >0.2 g/g) 2
Non-glomerular hematuria indicators:
- >80% normal-appearing red blood cells 2
- Bright red blood 2
- Associated flank pain, dysuria, or irritative voiding symptoms 2
If glomerular features are present, refer to nephrology for evaluation of glomerulonephritis, IgA nephropathy, Alport syndrome, or other renal parenchymal disease. 2, 3
Risk Stratification for Urologic Malignancy
For confirmed non-glomerular microscopic hematuria, stratify patients by malignancy risk:
High-risk features (require complete urologic evaluation):
- Age ≥60 years (males) or ≥60 years (females) 2, 4
- Smoking history >30 pack-years 2, 4
- Any history of gross hematuria (even if remote or self-limited) 1, 2
- Occupational exposure to benzenes, aromatic amines, or other chemicals/dyes 2, 4
- Irritative voiding symptoms (urgency, frequency, nocturia) without infection 2
- History of pelvic irradiation 3
- Chronic analgesic abuse 3
Intermediate-risk features:
Low-risk features:
- Males <40 years without other risk factors 2
- Females <50 years without other risk factors 2
- Never smoker or <10 pack-years 2
Complete Urologic Evaluation for High and Intermediate Risk
For all high-risk patients and most intermediate-risk patients, perform:
Upper Tract Imaging
Multiphasic CT urography is the preferred imaging modality (unenhanced, nephrographic, and excretory phases) to detect renal cell carcinoma, transitional cell carcinoma, and urolithiasis. 2, 3, 4
- If CT is contraindicated (renal insufficiency, contrast allergy), use MR urography or renal ultrasound with retrograde pyelography as alternatives, though these are less optimal. 2
- Renal ultrasound alone is insufficient for comprehensive upper tract evaluation. 2
Lower Tract Evaluation
Cystoscopy is mandatory for all patients with gross hematuria and for microscopic hematuria patients with risk factors. 1, 2, 3
- Flexible cystoscopy is preferred over rigid cystoscopy—it causes less pain, has fewer post-procedure symptoms, and demonstrates equivalent or superior diagnostic accuracy. 2, 3
- Cystoscopy visualizes bladder mucosa, urethra, and ureteral orifices to exclude transitional cell carcinoma. 2
Additional Testing
- Voided urine cytology should be obtained in high-risk patients to detect high-grade urothelial carcinomas and carcinoma in situ. 2, 3
- Do NOT obtain urinary cytology or urine-based molecular markers in the initial evaluation of low-risk microscopic hematuria—current guidelines do not recommend this. 1
- Assess serum creatinine to evaluate renal function. 2, 3
Management of Low-Risk Microscopic Hematuria
For patients without risk factors and with no identified benign cause:
Shared decision-making approach regarding whether to pursue complete urologic evaluation versus surveillance, as the malignancy risk is approximately 2.6-4% in this population. 2, 4
If surveillance is chosen:
- Repeat urinalysis at 6,12,24, and 36 months 2, 3
- Monitor blood pressure at each visit 2, 3
- Immediate re-evaluation is warranted if:
Nephrology Referral Indications
Refer to nephrology if:
- Persistent significant proteinuria (protein-to-creatinine ratio >0.2 g/g on three specimens) 2
- Red blood cell casts or >80% dysmorphic RBCs 2, 3
- Elevated creatinine or declining renal function 2, 4
- Hypertension with hematuria and proteinuria 2
- Hematuria persists with development of glomerular features during surveillance 2, 3
Critical Pitfalls to Avoid
Never screen asymptomatic adults with urinalysis for cancer detection—this leads to unnecessary cascades of testing and anxiety. 1
Never attribute hematuria to medications (including anticoagulants, antiplatelets, or Cialis)—these do not cause hematuria but may unmask underlying pathology. 1, 2
Never ignore gross hematuria, even if self-limited—30-40% malignancy risk mandates urgent evaluation. 1, 2
Never delay evaluation with repeated courses of antibiotics in patients with persistent hematuria despite appropriate antibiotic therapy—this delays cancer diagnosis and provides false reassurance. 2
Never obtain urine culture in truly asymptomatic patients—asymptomatic bacteriuria should not be treated and does not explain hematuria. 2
Do not defer evaluation in patients taking anticoagulation or antiplatelet therapy—evaluation should proceed regardless. 1, 2