Hematuria Evaluation and Management

Immediate Confirmation and Classification

Confirm true hematuria with microscopic urinalysis showing ≥3 red blood cells per high-power field (RBC/HPF) on a properly collected clean-catch midstream specimen before initiating any workup. 1, 2 Dipstick testing alone has only 65–99% specificity and produces false positives from myoglobin, hemoglobin, menstrual contamination, or other substances. 1

Distinguish Gross vs. Microscopic Hematuria

Gross (visible) hematuria carries a 30–40% malignancy risk and mandates urgent urologic referral within 24–48 hours for cystoscopy and upper tract imaging, even if bleeding appears self-limited. 1
Microscopic hematuria (≥3 RBC/HPF detected only under microscope) requires risk stratification before determining the extent of evaluation. 1

Risk Stratification for Microscopic Hematuria

Use the American Urological Association (AUA) risk categories to guide evaluation intensity: 1, 3

High-Risk Features (require full urologic workup: cystoscopy + CT urography)

Age ≥60 years (both men and women) 1, 3
Smoking history >30 pack-years 1, 3
Any history of gross hematuria (even if remote or self-limited) 1
Occupational exposure to bladder carcinogens (benzenes, aromatic amines, dyes) 1, 3
Irritative voiding symptoms (urgency, frequency, dysuria) without documented infection 1
Degree of hematuria >25 RBC/HPF 1

Intermediate-Risk Features (shared decision-making regarding cystoscopy/imaging)

Men age 40–59 years or women age ≥60 years with lower-risk features 1
Smoking history 10–30 pack-years 1
Hematuria 11–25 RBC/HPF 1

Low-Risk Features (may defer extensive imaging; consider observation)

Men <40 years or women <60 years 1
Never smoker or <10 pack-years 1
Hematuria 3–10 RBC/HPF 1

Differentiate Glomerular vs. Urologic Source

Before proceeding with urologic evaluation, assess for signs of glomerular (kidney parenchymal) disease: 1, 2

Glomerular Indicators (warrant nephrology referral)

>80% dysmorphic RBCs on phase-contrast microscopy 1
Red blood cell casts (pathognomonic for glomerulonephritis) 1
Significant proteinuria: spot urine protein-to-creatinine ratio >0.5 g/g (or >500 mg/24 hours) 1, 2
Elevated serum creatinine or declining renal function 1
Tea-colored or cola-colored urine (suggests glomerular bleeding) 1
Hypertension accompanying hematuria and proteinuria 1

If glomerular features are present, refer to nephrology in addition to completing urologic evaluation—malignancy can coexist with medical renal disease. 1

Urologic (Non-Glomerular) Indicators

Normal-shaped RBCs (>80% eumorphic) 1
Minimal or no proteinuria (<0.2 g/g) 1
Absence of red cell casts 1

Complete Urologic Evaluation (for High-Risk or Persistent Hematuria)

Upper Tract Imaging

Multiphasic CT urography (unenhanced, nephrographic, and excretory phases) is the preferred modality, with 96% sensitivity and 99% specificity for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis. 1, 3
If CT is contraindicated (severe renal insufficiency, contrast allergy, pregnancy), use MR urography or renal ultrasound with retrograde pyelography as alternatives. 1
Renal ultrasound alone is insufficient for comprehensive upper tract evaluation and misses small masses and urothelial lesions. 1

Lower Tract Evaluation

Flexible cystoscopy is mandatory for all patients with gross hematuria and for microscopic hematuria patients ≥40 years or with any high-risk features. 1, 3
Flexible cystoscopy provides equivalent or superior diagnostic accuracy to rigid cystoscopy with less patient discomfort. 1
Bladder cancer accounts for 30–40% of gross hematuria cases and 2.6–4% of microscopic hematuria cases; imaging alone cannot exclude bladder malignancy. 1

Adjunctive Testing

Voided urine cytology should be obtained in high-risk patients (age >60 years, smoking >30 pack-years, occupational exposures) to detect high-grade urothelial carcinomas and carcinoma in situ. 1
Do not use urine cytology or molecular markers as the initial evaluation tool—they are adjuncts only. 1

Laboratory Evaluation

Serum creatinine and BUN to assess renal function 1
Complete urinalysis with microscopy to examine for dysmorphic RBCs, casts, crystals, and degree of proteinuria 1
Urine culture if infection is suspected—obtain before starting antibiotics 1, 2

Special Clinical Scenarios

Hematuria with Concurrent Urinary Tract Infection (UTI)

Obtain urine culture before initiating antibiotics. 1, 2
Treat the UTI appropriately, then repeat urinalysis 6 weeks after completing antibiotics to confirm resolution of hematuria. 1, 2
If hematuria resolves after infection treatment in a low-risk patient, no further urologic workup is needed. 1, 2
If hematuria persists 6 weeks post-treatment, proceed immediately with full urologic evaluation (CT urography + cystoscopy). 1, 2
Never delay urologic evaluation in patients >35–40 years or with high-risk features while treating UTI—age alone is sufficient to warrant full workup. 1
Pyuria does not exclude malignancy; infection may mask cancer. 1

Hematuria in Patients on Anticoagulation/Antiplatelet Therapy

Do not attribute hematuria to anticoagulants or antiplatelet agents—these medications may unmask underlying pathology but do not cause hematuria. 1, 2
Evaluation must proceed identically to non-anticoagulated patients. 1

Transient Benign Causes to Exclude

Recent vigorous exercise 1
Sexual activity or trauma 1, 2
Menstruation (obtain catheterized specimen if clean-catch is unreliable) 1
Viral illness 2

If a benign transient cause is suspected, repeat urinalysis 48 hours after cessation of the activity. 2 If hematuria resolves, no further evaluation is needed in low-risk patients. 2

Follow-Up Protocol for Negative Initial Evaluation

If the complete urologic workup (cystoscopy + imaging) is negative but hematuria persists: 1, 2

Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit. 1, 2
After two consecutive negative annual urinalyses, further testing is unnecessary. 1
Consider repeat comprehensive evaluation (cystoscopy + imaging) within 3–5 years for persistent hematuria in high-risk patients. 1

Triggers for Immediate Re-Evaluation

Development of gross hematuria 1, 2
Significant increase in degree of microscopic hematuria 1, 2
New urologic symptoms (flank pain, irritative voiding, dysuria) 1, 2
Emergence of hypertension, proteinuria, or evidence of glomerular bleeding 1, 2

Nephrology Referral Indications

Refer to nephrology when any of the following are present: 1, 2

Protein-to-creatinine ratio >0.5 g/g (or >500 mg/24 hours), especially if persistent or rising 1, 2
>80% dysmorphic RBCs or presence of red cell casts 1
Elevated serum creatinine or declining renal function 1
Hypertension accompanying hematuria and proteinuria 1

Critical Pitfalls to Avoid

Never ignore gross hematuria, even if self-limited—30–40% malignancy risk mandates urgent urologic referral. 1
Do not rely solely on dipstick testing—confirm with microscopic urinalysis showing ≥3 RBC/HPF before initiating workup. 1
Do not defer evaluation due to anticoagulation—these medications unmask but do not cause hematuria. 1
**Do not assume age <40 years excludes malignancy**—high-risk features (smoking, occupational exposure, degree of hematuria >30 RBC/HPF) warrant full evaluation regardless of age. 1
Do not delay cancer diagnosis by treating presumed UTI without follow-up—persistent hematuria after infection treatment requires immediate urologic assessment. 1, 2
Imaging alone cannot exclude bladder cancer—cystoscopy is mandatory for complete evaluation. 1

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