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

Evaluation and Management of Hematuria

Initial Confirmation and Triage

All patients with gross hematuria require immediate urologic referral regardless of whether it is self-limited, while microscopic hematuria must first be confirmed with microscopic urinalysis showing ≥3 RBCs per high-power field before initiating any evaluation. 1, 2

• Do not rely on dipstick testing alone—confirm all heme-positive dipstick results with microscopic examination demonstrating ≥3 erythrocytes per high-powered field 1, 3
• Specifically ask all patients about any history of gross hematuria during routine review of systems, as visible blood significantly increases cancer risk (odds ratio 7.2) and is often underreported 1, 3
• Gross hematuria carries >10% risk of malignancy and mandates prompt urologic evaluation even if self-limited 1, 4

Exclude Benign Transient Causes

Before proceeding with extensive workup, rule out the following reversible causes 2, 3:

• Menstruation, vigorous exercise, sexual activity, trauma 2, 3
• Viral illness 3
• Urinary tract infection: obtain urine culture if suspected, treat appropriately, and repeat urinalysis 6 weeks after treatment to confirm resolution 3
• Repeat urinalysis 48 hours after cessation of the potential benign cause 3

Determine Glomerular vs. Non-Glomerular Source

Perform comprehensive urinalysis with sediment examination to assess 2, 3:

• Dysmorphic RBCs (>80% suggests glomerular source) 2, 3
• Red cell casts (pathognomonic for glomerular disease) 2, 3
• Proteinuria: quantify with 24-hour urine collection if dipstick shows persistent proteinuria 3
• Serum creatinine to assess renal function 2, 3

Nephrology Referral Criteria

Refer to nephrology if any of the following are present 2, 3:

• Proteinuria >500 mg/24 hours (or >1,000 mg/24 hours) 2, 3
• Red cell casts or predominantly dysmorphic RBCs (>80%) 2, 3
• Elevated serum creatinine 2, 3
• Development of hypertension with persistent hematuria 2, 3

Risk Stratification for Urologic Malignancy

High-Risk Factors Requiring Complete Urologic Evaluation

Patients with any of the following require cystoscopy and upper tract imaging 2, 3, 5:

• Age ≥40 years (or ≥60 years per AUA) 2, 3, 5
• Smoking history (severity depends on pack-years) 2, 3, 5
• Occupational exposure to chemicals/dyes (benzenes or aromatic amines) 2, 3
• History of gross hematuria 2, 3
• Irritative voiding symptoms 2, 3
• History of pelvic irradiation 2, 3
• Analgesic abuse 2, 3
• Male sex (higher prevalence of significant urologic disease) 5

Complete Urologic Evaluation for High-Risk Patients

Upper Tract Imaging

CT urography is the preferred imaging modality for comprehensive evaluation of the upper urinary tract to identify hydronephrosis, urinary calculi, and renal/ureteral lesions 2, 5

Cystoscopy

Cystoscopy is mandatory in all patients ≥40 years of age and in patients <40 years with risk factors for bladder cancer 2, 5

Urine Cytology

• Do not obtain urinary cytology or other urine-based molecular markers in the initial evaluation of hematuria 1
• Urine cytology is recommended only in patients with risk factors for transitional cell carcinoma (age >40 years, smoking, occupational exposures, pelvic irradiation, irritative voiding symptoms, history of gross hematuria, analgesic abuse) 2
• May be considered specifically for carcinoma in situ risk or irritative voiding symptoms 5

Critical Caveat: Anticoagulation is Not an Excuse

Pursue full evaluation of hematuria even if the patient is receiving antiplatelet or anticoagulant therapy—do not attribute hematuria solely to these medications without investigation 1, 3

Follow-Up Protocol for Negative Initial Workup

If initial urologic evaluation is negative but hematuria persists 2, 3:

• Repeat urinalysis at 6,12,24, and 36 months 2, 3
• Monitor blood pressure at each follow-up visit 2, 3
• Further workup is warranted if patient develops gross hematuria, significant increase in degree of microscopic hematuria, or new urologic symptoms 5

Common Pitfalls to Avoid

• Never use screening urinalysis for cancer detection in asymptomatic adults 1
• Do not delay evaluation in high-risk patients, as early detection of urologic malignancy significantly impacts mortality and morbidity 5
• Do not rely on dipstick alone—specificity is only 65-99% 5
• For high-risk patients, a single urinalysis with ≥3 RBC/HPF may warrant full evaluation rather than waiting for confirmation on multiple specimens 5