Microscopic Hematuria: 3–5 RBC/HPF
A finding of 3–5 red blood cells per high-power field on urine microscopy meets the diagnostic threshold for microscopic hematuria and warrants systematic evaluation to exclude urologic malignancy, urolithiasis, infection, and glomerular disease. 1, 2, 3
Clinical Significance
- Microscopic hematuria is definitively diagnosed at ≥3 RBCs/HPF on microscopic examination of a properly collected clean-catch midstream urine specimen. 1, 2, 3
- A count of 3–5 RBCs/HPF places the patient in the low-risk category for degree of hematuria according to AUA/SUFU risk stratification (3–10 RBCs/HPF = low risk), but age, smoking history, and other risk factors determine the intensity of workup—not RBC count alone. 1, 2
- Malignancy accounts for 2.6–4% of microscopic hematuria cases overall, but risk increases substantially with age >35–40 years, male gender, smoking history, and occupational chemical exposure. 1, 3, 4
Mandatory Confirmation Before Workup
- Do not initiate any urologic evaluation based on dipstick testing alone; dipstick has only 65–99% specificity and yields false positives from myoglobin, hemoglobin, menstrual blood, or contaminants. 1, 2
- Confirm microscopic hematuria with ≥3 RBCs/HPF on at least two of three properly collected specimens before proceeding with imaging or cystoscopy, unless high-risk features are present (gross hematuria, age ≥60 years, smoking >30 pack-years, occupational exposures, irritative voiding symptoms without infection). 1, 2, 3
Risk Stratification Algorithm
Step 1: Assess Age
- Males ≥60 years or females ≥60 years = HIGH RISK → proceed directly to full urologic evaluation (cystoscopy + CT urography). 1, 2
- Males 40–59 years or females with additional risk factors = INTERMEDIATE RISK → shared decision-making regarding cystoscopy and imaging. 1, 2
- Males <40 years and females <60 years with no risk factors = LOW RISK → may defer extensive imaging but still require evaluation if hematuria persists. 1, 2
Step 2: Assess Smoking History
- >30 pack-years = HIGH RISK → full urologic evaluation mandatory. 1, 2
- 10–30 pack-years = INTERMEDIATE RISK → shared decision-making. 1, 2
- <10 pack-years or never smoker = LOW RISK. 1, 2
Step 3: Assess Additional High-Risk Features
- History of gross hematuria (even if remote) = HIGH RISK. 1, 2
- Occupational exposure to benzenes, aromatic amines, or other bladder carcinogens = HIGH RISK. 1, 2, 3
- Irritative voiding symptoms (urgency, frequency, dysuria) without documented infection = HIGH RISK. 1, 2
Distinguishing Glomerular vs. Urologic Source
Glomerular Indicators (Nephrology Referral + Urologic Evaluation)
- >80% dysmorphic RBCs on urinary sediment examination with phase-contrast microscopy. 1, 3
- Red blood cell casts (pathognomonic for glomerular disease). 1, 3
- Significant proteinuria: spot urine protein-to-creatinine ratio >0.5 g/g (or >500 mg/24 hours). 1, 3
- Elevated serum creatinine or declining eGFR. 1, 3
- Tea-colored or cola-colored urine. 1
Urologic Indicators (Urologic Evaluation Only)
- <17% dysmorphic RBCs or normal-shaped RBCs. 3
- Minimal or no proteinuria (protein-to-creatinine ratio <0.2 g/g). 1, 3
- Normal renal function (normal serum creatinine and eGFR). 1, 3
Critical Pitfall: The presence of glomerular features does not eliminate the need for urologic evaluation—malignancy can coexist with medical renal disease. 1
Complete Urologic Evaluation Protocol
For Intermediate- and High-Risk Patients:
Upper Tract Imaging
- Multiphasic CT urography (unenhanced, nephrographic, and excretory phases) is the preferred imaging modality; it provides 96% sensitivity and 99% specificity for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis. 1, 3, 4
- Alternative imaging (if CT contraindicated): MR urography or renal ultrasound with retrograde pyelography. 1
Lower Tract Evaluation
- Flexible cystoscopy is mandatory for all patients ≥35–40 years with microscopic hematuria or any patient with high-risk features, to visualize bladder mucosa, urethra, and ureteral orifices. 1, 2, 3, 4
- Flexible cystoscopy is preferred over rigid cystoscopy because it causes less pain and has equivalent or superior diagnostic accuracy. 1, 3
Urine Cytology
- No longer recommended as part of routine evaluation unless high-risk features are present (age >60 years, smoking >30 pack-years, occupational exposures). 1, 4
Special Clinical Scenarios
Urinary Tract Infection
- Treat infection appropriately and repeat urinalysis 6 weeks after treatment completion; if hematuria resolves, no further evaluation is needed. 1, 3, 4
- If hematuria persists after treating infection, proceed with full urologic evaluation—infection does not exclude concurrent malignancy. 1, 3
Anticoagulation/Antiplatelet Therapy
- Do not defer evaluation; these medications may unmask underlying pathology but do not cause hematuria. 1, 3
- Patients on anticoagulation should undergo the same complete evaluation as patients not on these medications. 1, 3
Transient Causes
- Exclude recent vigorous exercise, sexual activity, viral illness, trauma, or menstruation; if history suggests benign transient causes, repeat urinalysis 48 hours after cessation of the activity. 3
- If hematuria resolves after eliminating transient causes, no further evaluation is needed. 3
Follow-Up Protocol for Negative Initial Evaluation
- Repeat urinalysis at 6,12,24, and 36 months with blood pressure monitoring at each visit. 1, 2, 3
- After two consecutive negative annual urinalyses, further testing is unnecessary. 1, 2
- Immediate re-evaluation is warranted if:
- Consider repeat anatomic evaluation (imaging and/or cystoscopy) within 3–5 years if hematuria persists in high-risk patients. 1, 2, 3
Common Pitfalls to Avoid
- Never dismiss microscopic hematuria in patients >35 years—malignancy risk rises markedly after age 35–40 and warrants full evaluation. 1, 3, 4
- Do not rely solely on dipstick testing; confirm with microscopic urinalysis showing ≥3 RBCs/HPF before initiating workup. 1, 2
- Do not assume anticoagulation is the cause; complete the recommended urologic work-up regardless. 1, 3
- Do not skip cystoscopy in favor of imaging alone—bladder cancer (the most common malignancy in hematuria patients) requires direct visualization. 1, 3, 4