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

Management of Hematuria (Blood in Urine)

Confirm true hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field before initiating any workup, then proceed with urgent urologic evaluation for gross hematuria or risk-stratified evaluation for microscopic hematuria. 1

Initial Confirmation and Assessment

Do not rely on dipstick testing alone—dipstick has only 65-99% specificity and requires microscopic confirmation with ≥3 RBCs per high-power field on at least two of three properly collected clean-catch midstream urine specimens. 1, 2

Exclude Benign Transient Causes First:

• Recent vigorous exercise (can cause transient hematuria) 1
• Menstruation in women (causes contamination) 1
• Recent sexual activity or minor trauma 2
• Viral illness 2

If a benign transient cause is suspected, repeat urinalysis 48 hours after cessation of the activity—if hematuria resolves, no further evaluation is needed. 2

Critical Rule: Never attribute hematuria to anticoagulation or antiplatelet therapy

These medications may unmask underlying pathology but do not cause hematuria themselves—evaluation must proceed regardless. 1, 2

Distinguish Between Gross and Microscopic Hematuria

Gross (Visible) Hematuria:

• Carries 30-40% risk of malignancy 1, 3
• Requires urgent urologic referral immediately, even if self-limited 1, 3
• All patients need cystoscopy and CT urography regardless of age or other factors 1, 3

Microscopic Hematuria:

• Carries 2.6-4% overall malignancy risk (higher in specific risk groups) 1, 2
• Requires risk stratification before determining evaluation pathway 1, 2

Risk Stratification for Microscopic Hematuria

High-Risk Features (Require Full Urologic Evaluation):

• Age ≥60 years (males or females) 1, 2
• Smoking history >30 pack-years 1, 2

• 25 RBCs per high-power field 1, 2

• Any history of gross hematuria 1, 2
• Occupational exposure to benzenes, aromatic amines, or other chemicals/dyes 1, 2, 3
• Irritative voiding symptoms (urgency, frequency, nocturia) without infection 1, 2

Intermediate-Risk Features:

• Women age 50-59 years or men age 40-59 years 1, 2
• Smoking history 10-30 pack-years 1, 2
• 11-25 RBCs per high-power field 1, 2

Low-Risk Features:

• Women <50 years or men <40 years 1, 2
• Never smoker or <10 pack-years 1, 2
• 3-10 RBCs per high-power field 1, 2

Determine Source: Glomerular vs. Non-Glomerular

Glomerular Source Indicators:

• Tea-colored or cola-colored urine 1, 3
• Significant proteinuria (>500 mg/24 hours or protein-to-creatinine ratio >0.5 g/g) 1, 2
• Dysmorphic RBCs >80% on microscopy 1, 2
• Red blood cell casts (pathognomonic for glomerular disease) 1, 2
• Elevated serum creatinine 1, 2

If glomerular features present: Refer to nephrology in addition to completing urologic evaluation—both evaluations should proceed as malignancy can coexist with medical renal disease. 1, 2

Non-Glomerular (Urologic) Source Indicators:

• Normal-shaped RBCs (>80%) 1
• Minimal or no proteinuria 1, 3
• Normal serum creatinine 1, 3
• Bright red blood 1

Complete Urologic Evaluation Protocol

For High-Risk Patients or Gross Hematuria:

1. Upper Tract Imaging:

   • Multiphasic CT urography is the preferred modality (detects renal cell carcinoma, transitional cell carcinoma, and urolithiasis) 1, 2, 4
   • Includes unenhanced, nephrographic, and excretory phases 1
   • Alternative: MR urography if CT contraindicated 1, 3
   • Renal ultrasound alone is insufficient for comprehensive evaluation 1

2. Lower Tract Evaluation:

   • Cystoscopy is mandatory for all gross hematuria and high-risk microscopic hematuria 1, 2
   • Flexible cystoscopy preferred over rigid (less pain, equivalent diagnostic accuracy) 1, 2

3. Laboratory Testing:

   • Serum creatinine to assess renal function 1, 2, 3
   • Complete urinalysis with microscopy 1, 2
   • Urine culture if infection suspected (obtain before antibiotics) 1, 2
   • Voided urine cytology in high-risk patients (age >80 years, high-grade tumor concern) 1, 3

For Intermediate-Risk Patients:

Cystoscopy with urinary tract imaging through shared decision-making. 1, 2

For Low-Risk Patients:

May undergo repeat urinalysis in 6 months or proceed with evaluation based on patient preference. 2

Special Consideration: Hematuria with Urinary Tract Infection

If UTI is suspected or confirmed:

• Obtain urine culture before starting antibiotics 1, 2
• Treat infection appropriately 2
• Repeat urinalysis 6 weeks after completing antibiotic treatment 2
• If hematuria resolves with treatment, no additional evaluation needed 2
• If hematuria persists after treating infection, proceed with full urologic evaluation—do not prescribe additional antibiotics as this delays cancer diagnosis 1, 2

Follow-Up Protocol for Negative Initial Evaluation

If complete workup is negative but hematuria persists:

• Repeat urinalysis at 6,12,24, and 36 months 1, 2, 3
• Monitor blood pressure at each visit 1, 2, 3
• Consider repeat complete evaluation within 3-5 years for persistent hematuria in high-risk patients 1, 2
• After two consecutive negative annual urinalyses, no further testing needed 1

Immediate Re-Evaluation Required If:

• Gross hematuria develops 1, 2, 3
• Significant increase in degree of microscopic hematuria 1, 2
• New urologic symptoms appear 1, 2
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2

Critical Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited—30-40% malignancy risk mandates urgent urologic referral 1, 3
• Never defer evaluation due to anticoagulation—these medications unmask but do not cause hematuria 1, 2
• Never rely solely on dipstick—confirm with microscopic urinalysis showing ≥3 RBCs/HPF 1, 2
• Never assume UTI explains persistent hematuria—if hematuria persists 6 weeks after treating infection, full urologic evaluation is required 2
• Never delay urologic referral in elderly patients—age ≥60 years is automatically high-risk 1, 2, 3
• Hematuria can precede bladder cancer diagnosis by many years—long-term surveillance is essential in high-risk patients 1