How to approach a patient presenting with hematuria?

Approach to the Patient with Blood in the Urine

All patients with gross hematuria require urgent urologic evaluation with cystoscopy and upper tract imaging (CT urography), regardless of whether the bleeding is self-limited or the patient is on anticoagulation, because the malignancy risk exceeds 10-30%. 1, 2, 3

Initial Confirmation and Classification

Confirm true hematuria before proceeding:

• Verify dipstick-positive results with microscopic urinalysis showing ≥3 red blood cells per high-power field (RBC/HPF) on at least two of three properly collected clean-catch midstream specimens 1, 2
• Dipstick tests have only 65-99% specificity and can produce false positives from myoglobin, hemoglobin, or menstrual contamination 1
• 0-2 RBCs/HPF is within normal range and does not warrant urologic workup 1

Classify the hematuria:

• Gross (macroscopic) hematuria: Visible blood in urine; 30-40% malignancy risk 1, 2
• Microscopic hematuria: ≥3 RBCs/HPF; 0.5-5% malignancy risk 1, 2

Critical Rule: Never Defer Evaluation

Anticoagulation or antiplatelet therapy does not explain hematuria and should never defer evaluation—these medications may unmask underlying pathology but do not cause hematuria themselves. 1, 2, 3

Determine the Source: Glomerular vs. Non-Glomerular

Examine urinary sediment and associated findings:

Glomerular Source Indicators:

• Tea-colored urine (not bright red) 1

• 80% dysmorphic red blood cells on microscopy 1

• Red blood cell casts (pathognomonic for glomerular disease) 1
• Significant proteinuria (protein-to-creatinine ratio >0.2 g/g) 1
• Elevated serum creatinine or declining renal function 1

Non-Glomerular Source Indicators:

• Bright red blood or clots 1

• 80% normal (non-dysmorphic) red blood cells 1

• Minimal or no proteinuria 1
• Normal renal function 1

Risk Stratification for Malignancy (Non-Glomerular Hematuria)

The American Urological Association stratifies patients into risk categories:

High-Risk Features (require full urologic evaluation):

• Age: Men ≥60 years, Women ≥60 years 1
• Smoking history >30 pack-years 1
• History of gross hematuria 1, 2
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 1
• Irritative voiding symptoms without infection 1
• History of urologic disorders 1
• ≥25 RBCs/HPF on microscopy 1

Intermediate-Risk Features:

• Age: Men 40-59 years, Women <60 years 1
• Smoking history 10-30 pack-years 1
• 11-25 RBCs/HPF 1

Low-Risk Features:

• Age: Men <40 years 1
• Never smoker or <10 pack-years 1
• 3-10 RBCs/HPF 1

Complete Urologic Evaluation for Non-Glomerular Hematuria

For all gross hematuria and high-risk microscopic hematuria:

Upper Tract Imaging:

• Multiphasic CT urography is the preferred imaging modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 2, 3
• Traditional intravenous urography (IVU) remains acceptable but has limited sensitivity for small renal masses 1
• Renal ultrasound alone is insufficient for comprehensive upper tract evaluation 1

Lower Tract Evaluation:

• Cystoscopy is mandatory for all patients with gross hematuria and intermediate-to-high-risk microscopic hematuria 1, 2, 3
• Flexible cystoscopy is preferred over rigid cystoscopy (less pain, equivalent or superior diagnostic accuracy) 1
• Do not omit cystoscopy based on negative imaging alone 3

Laboratory Testing:

• Serum creatinine, BUN, complete metabolic panel 1
• Complete urinalysis with microscopy 1
• Urine culture if infection suspected (preferably before antibiotics) 1, 3
• Do not obtain urinary cytology or urine-based molecular markers in the initial evaluation (not recommended by current guidelines) 1, 2

Nephrology Evaluation for Glomerular Hematuria

Refer to nephrology when:

• Red blood cell casts or >80% dysmorphic RBCs present 1
• Persistent significant proteinuria (protein-to-creatinine ratio >0.2 for three specimens) 1
• Elevated creatinine or declining renal function 1
• Hypertension with hematuria and proteinuria 1

Additional nephrology workup includes:

• Complement levels (C3, C4) to evaluate for post-infectious glomerulonephritis or lupus nephritis 1
• Antinuclear antibody (ANA) and ANCA testing if vasculitis suspected 1
• Renal ultrasound to evaluate kidney size, echogenicity, and structural abnormalities 1
• Consider renal biopsy for definitive diagnosis 1

Special Clinical Scenarios

Benign Causes to Consider (but still evaluate if persistent):

• Urinary tract infection: Obtain urine culture; re-evaluate after treatment to ensure resolution 1, 3
• Urolithiasis: Painful hematuria with flank pain; CT urography diagnostic 1
• Vigorous exercise: Transient hematuria that resolves with rest 1
• Menstruation: Can contaminate urine samples in women; repeat specimen 1
• Benign prostatic hyperplasia: Can cause hematuria but does not exclude concurrent malignancy 1

Trauma-Related Hematuria:

• Gross hematuria or 4+ hematuria after blunt trauma requires contrast-enhanced CT 1
• Blood at urethral meatus with pelvic fractures requires retrograde urethrography before catheter placement 1
• Isolated microscopic hematuria without clinical findings of visceral trauma does not need emergency investigation 1

Follow-Up Protocol for Negative Initial Evaluation

If initial workup is negative but hematuria persists:

• Repeat urinalysis, blood pressure measurement at 6,12,24, and 36 months 1
• Immediate re-evaluation warranted if: 1
  • Gross hematuria develops
  • Significant increase in degree of microscopic hematuria
  • New urologic symptoms appear
  • Development of hypertension, proteinuria, or evidence of glomerular bleeding

Hematuria can precede bladder cancer diagnosis by many years, making long-term surveillance essential in high-risk patients. 1

Common Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited—30-40% malignancy risk mandates urgent urologic referral 1, 2, 3
• Never attribute hematuria solely to anticoagulation—full urologic evaluation is mandatory 1, 2, 3
• Never assume infection explains gross hematuria without follow-up confirmation after treatment 3
• Never skip cystoscopy based on negative imaging alone for hematuria evaluation 3
• Never obtain urinary cytology in initial evaluation—not recommended by current guidelines 1, 2
• Dipstick positivity alone should not lead to imaging without microscopic confirmation of ≥3 RBCs/HPF 1