What is the appropriate workup for a patient presenting with hematuria (blood in urine)?

Hematuria Workup

All patients with confirmed hematuria (≥3 RBCs per high-power field on microscopic examination) require systematic evaluation to exclude malignancy and other serious pathology, with the workup intensity determined by risk stratification based on age, sex, smoking history, and whether the hematuria is gross or microscopic. 1, 2

Initial Confirmation and Documentation

• Confirm dipstick findings with microscopic urinalysis showing ≥3 RBCs per high-power field on at least two of three properly collected clean-catch midstream urine specimens before initiating any workup 1, 2
• Dipstick tests have only 65-99% specificity and can produce false positives from myoglobin, hemoglobin, or other substances 1
• Document whether hematuria is gross (visible) or microscopic (only detected under microscope) 1
• Note urine color: tea-colored or cola-colored suggests glomerular source, while bright red suggests lower urinary tract bleeding 1, 3

Risk Stratification for Malignancy

Use the AUA/SUFU risk stratification system to determine evaluation intensity 2:

High-Risk Features (requires complete urologic evaluation):

• Any gross hematuria (30-40% malignancy risk) 1, 3
• Males ≥60 years 1
• Smoking history >30 pack-years 1, 2
• Occupational exposure to benzenes or aromatic amines 1, 3
• History of prior gross hematuria 1
• Irritative voiding symptoms without infection 1

Intermediate-Risk Features:

• Males 40-59 years 1
• Women ≥60 years 1
• Smoking history 10-30 pack-years 1

Low-Risk Features:

• Women <60 years 1
• Males <40 years 1
• Never smoker or <10 pack-years 1
• 3-10 RBCs/HPF 1

Distinguishing Glomerular from Non-Glomerular Sources

Before proceeding with urologic workup, assess for glomerular disease 1, 2:

Features Suggesting Glomerular Source (requires nephrology referral):

• >80% dysmorphic RBCs on phase contrast microscopy 1, 3
• Red blood cell casts (pathognomonic for glomerular disease) 1, 3
• Significant proteinuria (protein-to-creatinine ratio >0.2 g/g) 1
• Tea-colored or cola-colored urine 1, 3
• Elevated serum creatinine or declining renal function 1
• Hypertension accompanying hematuria 1

Laboratory Tests for Glomerular Assessment:

• Complete urinalysis with microscopic sediment examination 1, 2
• Spot urine protein-to-creatinine ratio 1
• Serum creatinine, BUN, complete metabolic panel 1, 2
• If glomerular disease suspected: complement levels (C3, C4), ANA, ANCA 1

Complete Urologic Evaluation (for Non-Glomerular Hematuria)

All high-risk patients and most intermediate-risk patients require both upper and lower tract evaluation 1, 2:

Upper Tract Imaging:

• Multiphasic CT urography is the preferred modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis 1, 2
• CT urography should include unenhanced, nephrographic phase, and excretory phase images 1
• If CT contraindicated: MR urography or renal ultrasound with retrograde pyelography (though less optimal) 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/high-risk microscopic hematuria 1, 2
• Flexible cystoscopy is preferred over rigid cystoscopy (less pain, equivalent or superior diagnostic accuracy) 1
• Cystoscopy evaluates bladder mucosa, urethra, and ureteral orifices for transitional cell carcinoma 1

Additional Testing:

• Voided urine cytology in high-risk patients to detect high-grade urothelial carcinomas and carcinoma in situ 1
• Urine culture if infection suspected (preferably before antibiotics) 1

Special Clinical Scenarios

Anticoagulation/Antiplatelet Therapy:

• Never attribute hematuria to anticoagulation or antiplatelet medications 1, 3
• These medications may unmask underlying pathology but do not cause hematuria themselves 1, 3
• Proceed with full evaluation regardless of anticoagulation status 1

Urinary Tract Infection:

• If UTI suspected, obtain urine culture before antibiotics 1
• Persistent hematuria after appropriate antibiotic therapy requires full urologic evaluation 1
• Do not prescribe additional antibiotics without completing cancer workup 1

Trauma-Related Hematuria:

• Gross hematuria after trauma requires contrast-enhanced CT 1
• Blood at urethral meatus with pelvic fracture 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 complete workup is negative but hematuria persists 1, 2:

• Repeat urinalysis at 6,12,24, and 36 months 1, 2
• Monitor blood pressure at each visit 1, 2
• Consider nephrology referral if hematuria persists with development of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2

Immediate Re-Evaluation Required If:

• Recurrent gross hematuria develops 1
• Significant increase in degree of microscopic hematuria 1
• New urologic symptoms appear 1
• Development of hypertension, proteinuria, or declining renal function 1

Critical Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited – it carries a 30-40% malignancy risk and requires urgent urologic referral 1, 3
• Do not defer evaluation in patients on anticoagulation – these medications unmask rather than cause hematuria 1, 3
• Do not treat asymptomatic bacteriuria in patients with hematuria – this delays cancer diagnosis and provides false reassurance 1
• Do not rely on dipstick alone – always confirm with microscopic examination showing ≥3 RBCs/HPF 1, 2
• Do not skip cystoscopy in high-risk patients – bladder cancer is the most frequently diagnosed malignancy in hematuria cases 1, 3