What is the step‑by‑step approach to evaluating and managing gross or microscopic hematuria, including history, physical exam, laboratory tests, imaging, and referral?

Approach to Hematuria

Begin by confirming true hematuria 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—dipstick testing alone has only 65-99% specificity and should never trigger a full workup without microscopic confirmation. 1

Initial Confirmation and Risk Stratification

Confirm True Hematuria

• Obtain microscopic urinalysis on properly collected specimens; dipstick positivity from myoglobin, hemoglobin, or menstrual contamination produces false positives 1
• Require ≥3 RBC/HPF on microscopy before proceeding with any imaging or invasive procedures 1
• In women, perform urethral and vaginal examination to exclude local contamination if clean-catch specimens are unreliable 1

Distinguish Gross vs. Microscopic Hematuria

• Gross (visible) hematuria carries a 30-40% malignancy risk and mandates urgent urologic referral within 24-48 hours, even if self-limited 1, 2
• Microscopic hematuria carries 0.5-5% overall cancer risk, but 7-20% in higher-risk subgroups 1
• Any history of prior gross hematuria automatically elevates cancer risk to >10% even if current presentation is microscopic 2

Exclude Transient Benign Causes

• Recent vigorous exercise, sexual activity, viral illness, trauma, or menstruation can cause self-limited hematuria 1
• If history suggests transient causes, repeat urinalysis 48 hours after cessation of the activity 1
• If hematuria resolves after eliminating transient causes, no further evaluation is needed 1

History: Key Risk Factors for Malignancy

High-Risk Features (Require Full Urologic Evaluation)

• Age ≥60 years (both men and women) 1
• Smoking history >30 pack-years 1
• Occupational exposure to benzenes, aromatic amines, or other bladder carcinogens 1
• History of gross hematuria (even if remote) 2
• Irritative voiding symptoms (urgency, frequency, nocturia) without documented infection 1
• Degree of microscopic hematuria >25 RBC/HPF 1

Intermediate-Risk Features (Shared Decision-Making)

• Age 40-59 years (men) 1
• Smoking history 10-30 pack-years 1

Symptoms Suggesting Specific Etiologies

• Tea-colored or cola-colored urine suggests glomerular disease and warrants nephrology referral in addition to urologic evaluation 1
• Flank pain with hematuria suggests urolithiasis or renal mass 1
• Dysuria, urgency, frequency, and fever suggest urinary tract infection 1
• Painless gross hematuria has stronger association with cancer than hematuria with flank pain 2

Physical Examination

Focused Examination Elements

• Vital signs including blood pressure (hypertension accompanying hematuria suggests glomerular disease) 1
• Abdominal examination for masses, flank tenderness, or palpable bladder 3
• Digital rectal examination in men to assess prostate (abnormal exam suspicious for prostate cancer requires immediate urologic referral) 3
• Cardiovascular examination if glomerulonephritis suspected (assess for volume overload, hypertension) 1
• In women, urethral and vaginal examination to exclude local contamination 1

Laboratory Tests

Initial Laboratory Workup

• Microscopic urinalysis with sediment examination to assess for dysmorphic RBCs (>80% suggests glomerular origin), red cell casts (pathognomonic for glomerular disease), white blood cells, bacteria, and crystals 1
• Spot urine protein-to-creatinine ratio to quantify proteinuria (normal <0.2 g/g; >0.5 g/g strongly suggests renal parenchymal disease) 1
• Serum creatinine and complete metabolic panel to assess renal function 1
• Urine culture if infection suspected, preferably before initiating antibiotics 1

Distinguishing Glomerular from Non-Glomerular Sources

Glomerular indicators (warrant nephrology referral in addition to urologic evaluation):

• Dysmorphic RBCs >80% on urinary sediment 1
• Red cell casts (pathognomonic for glomerular disease) 1
• Significant proteinuria (protein-to-creatinine ratio >0.5 g/g) 1
• Elevated serum creatinine or declining renal function 1
• Tea-colored or cola-colored urine 1

Non-glomerular indicators (proceed with urologic evaluation):

• Normal-shaped RBCs with minimal proteinuria 1
• Absence of dysmorphic RBCs or casts 1
• Bright red blood suggesting lower urinary tract source 1

Additional Testing for Glomerular Disease (If Indicated)

• Complement levels (C3, C4) to evaluate for post-infectious glomerulonephritis or lupus nephritis 1
• Antinuclear antibody (ANA) and anti-double-stranded DNA if lupus suspected 1
• ANCA testing (PR3, MPO) if vasculitis suspected 1
• Complete blood count with platelets to evaluate for coagulopathy 1

Testing NOT Recommended in Initial Evaluation

• Do not obtain urine cytology or urine-based molecular markers in the initial evaluation of hematuria 1, 2
• These tests have poor sensitivity for low-grade tumors and should not replace cystoscopy 1

Imaging

For High-Risk Patients (Age ≥60, Smoking >30 Pack-Years, Gross Hematuria, or Other High-Risk Features)

Multiphasic CT urography is the preferred imaging modality with 96% sensitivity and 99% specificity for urothelial malignancy 1

• Includes unenhanced phase (detects calculi), nephrographic phase (evaluates renal parenchyma and masses), and excretory phase (assesses urothelium of upper tracts, ureters, and bladder) 1
• Detects renal cell carcinoma, transitional cell carcinoma, and urolithiasis in a single study 1

Alternative imaging when CT contraindicated:

• MR urography for patients with renal insufficiency or contrast allergy 1
• Renal ultrasound with retrograde pyelography (less optimal but acceptable) 1

Critical pitfall: Renal ultrasound alone is insufficient for comprehensive upper tract evaluation and detects only 75% of urinary tract stones and 38% of ureteral stones 1

For Intermediate-Risk Patients

• Shared decision-making regarding CT urography versus ultrasound 1
• Consider patient preferences, radiation exposure, and cost 1

For Low-Risk Patients Without Benign Explanation

• Renal and bladder ultrasound may be appropriate first-line imaging 1
• If hematuria persists after negative ultrasound, proceed to CT urography 1

Pediatric Imaging Considerations

• Isolated microscopic hematuria without proteinuria in children does not require imaging 4, 1
• Renal and bladder ultrasound is appropriate for children with gross hematuria to exclude nephrolithiasis, anatomic abnormalities, and rarely tumors 4, 1
• CT is not appropriate for isolated nonpainful, nontraumatic hematuria in children 4
• In traumatic hematuria with congenital renal abnormalities, multiorgan injury, deceleration injury, localized flank pain, or ecchymosis, perform contrast-enhanced CT even with only microscopic hematuria 4

Cystoscopy

Indications for Cystoscopy

Mandatory cystoscopy for:

• All patients with gross hematuria regardless of age 1
• All patients ≥40 years with microscopic hematuria 1
• Microscopic hematuria patients with any high-risk features (smoking, occupational exposure, irritative symptoms) 1

Flexible cystoscopy is preferred over rigid cystoscopy because it causes less pain, has fewer post-procedure symptoms, and demonstrates equivalent or superior diagnostic accuracy (87-100% sensitivity, 98-100% negative predictive value) 1

Critical Pitfall

Imaging alone cannot substitute for cystoscopy—bladder cancer (the most common malignancy in hematuria patients) must be directly visualized, and CT cannot reliably exclude bladder malignancy 1

Management of Urinary Tract Infection with Hematuria

If Infection Suspected

• Obtain urine culture before initiating antibiotics 1
• Treat appropriately and repeat urinalysis 6 weeks after treatment 1
• If hematuria resolves with infection treatment in a low-risk patient, no additional evaluation is necessary 1
• If hematuria persists after treating infection, proceed with full urologic evaluation 1

Critical Pitfall

Pyuria, dysuria, or positive urine culture does not exclude concurrent urinary tract malignancy—infection may mask cancer, and persistent hematuria after treatment mandates complete urologic workup 1

Anticoagulation Considerations

Anticoagulant and antiplatelet medications do not cause hematuria—they may only unmask underlying pathology that requires investigation. 1, 2, 3

• Proceed with full urologic evaluation regardless of anticoagulation status 1, 2, 3
• Do not defer or delay evaluation based on medication use 1, 2, 3

Referral Guidelines

Immediate Urologic Referral (Within 24-48 Hours)

• Any gross hematuria in adults (30-40% malignancy risk) 1, 2, 3
• Microscopic hematuria with high-risk features (age ≥60, smoking >30 pack-years, occupational exposure, irritative symptoms, history of gross hematuria) 1, 3
• Hematuria with abnormal digital rectal exam suspicious for prostate cancer 3
• Hematuria with bladder wall thickening or other anatomic abnormalities on imaging 1

Nephrology Referral (In Addition to Urologic Evaluation)

• Protein-to-creatinine ratio >0.5 g/g (or >500 mg/24 hours) 1
• Dysmorphic RBCs >80% or presence of red cell casts 1
• Elevated serum creatinine or declining renal function 1
• Hypertension accompanying hematuria and proteinuria 1
• eGFR <30 mL/min/1.73 m² 3

Critical point: The presence of glomerular features does not eliminate the need for urologic evaluation—malignancy can coexist with medical renal disease 1

Follow-Up Protocol for Negative Initial Evaluation

If Complete Workup Is Negative but Hematuria Persists

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

Immediate Re-Evaluation Warranted If:

• Gross hematuria develops 1
• Significant increase in degree of microscopic hematuria 1
• New urologic symptoms appear (irritative voiding, flank pain, dysuria) 1
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 1

Common Pitfalls to Avoid

• Never ignore gross hematuria, even if self-limited—30-40% malignancy risk mandates urgent urologic referral 1, 2
• 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 may unmask underlying pathology but do not cause hematuria 1, 2, 3
• Do not assume infection explains hematuria without follow-up—persistent hematuria after treating infection requires full urologic evaluation 1
• Do not omit cystoscopy based on negative imaging alone—bladder cancer must be directly visualized 1
• Do not attribute hematuria to benign prostatic hyperplasia without proving prostatic origin—gross hematuria from BPH must be confirmed through appropriate evaluation 1
• Hematuria can precede bladder cancer diagnosis by many years—long-term surveillance is essential in high-risk elderly patients 1
• Delays in diagnosis beyond 9 months are associated with worse cancer-specific survival—prompt evaluation is critical 1