What does it mean if a urinalysis is negative for blood but red blood cells (RBCs) are present?

Understanding Urinalysis Results: RBCs Present but Negative for Blood

A urinalysis showing red blood cells (RBCs) but testing negative for blood typically indicates the presence of intact RBCs without free hemoglobin, which can occur in several clinical scenarios that require appropriate evaluation based on risk stratification. 1

Why This Discrepancy Occurs

This apparent contradiction can happen for several reasons:

• Dipstick sensitivity limitations: The dipstick test detects free hemoglobin/myoglobin but may miss intact RBCs if there are fewer than 5-10 RBCs/HPF
• Laboratory processing time: RBCs may lyse between collection and microscopic examination
• Specimen concentration: Dilute urine may show fewer RBCs than are actually present
• Non-hemoglobin RBCs: In some conditions, RBCs may be present but contain little hemoglobin

Clinical Significance and Evaluation

The presence of RBCs in urine, even with a negative dipstick, still constitutes microhematuria and requires appropriate evaluation:

Risk Stratification Approach

According to the AUA/SUFU guidelines, patients with ≥3 RBCs/HPF should be risk-stratified into low, intermediate, or high-risk categories based on:

1. Age:

   • Low risk: Women <50 years, men <40 years
   • Intermediate risk: Women 50-59 years, men 40-59 years
   • High risk: Anyone ≥60 years

2. Smoking history:

   • Low risk: Never smoker or <10 pack-years
   • Intermediate risk: 10-30 pack-years
   • High risk: >30 pack-years

3. RBC count:

   • Low risk: 3-10 RBC/HPF
   • Intermediate risk: 11-25 RBC/HPF
   • High risk: >25 RBC/HPF

4. Other factors:

   • History of gross hematuria (high risk)
   • Additional risk factors for urothelial cancer 1, 2

Evaluation Algorithm

1. Initial assessment:

   • Determine if RBCs are dysmorphic (suggesting glomerular source) or isomorphic (suggesting lower urinary tract source)
   • Check for proteinuria, RBC casts, or renal insufficiency which suggest renal parenchymal disease 1

2. For suspected glomerular bleeding:

   • Evaluate for systemic diseases (lupus, vasculitis)
   • Consider nephrology referral
   • Renal biopsy may be indicated

3. For suspected non-glomerular source:

   • Complete urologic evaluation based on risk stratification
   • High and intermediate risk: CT urography and cystoscopy
   • Low risk: Consider repeat urinalysis in 6 months 1

Special Considerations

Potential False Positives for RBCs

• Rhabdomyolysis: Can cause positive dipstick for blood with absent RBCs (due to myoglobinuria) 3
• Concentrated specimen techniques: May increase RBC cast detection but are not routinely performed 4

Follow-up Recommendations

For patients with a negative evaluation:

• Most can be safely discharged from urologic care
• Consider repeat UA for high-risk patients (heavy smokers, multiple risk factors)
• Any development of gross hematuria, increased microhematuria, or new urologic symptoms warrants prompt re-evaluation 1

Common Pitfalls to Avoid

1. Don't ignore microhematuria even with negative dipstick - the presence of RBCs still requires evaluation
2. Don't assume benign causes without appropriate risk-stratified evaluation
3. Don't over-test low-risk patients with persistent stable microhematuria after negative evaluation
4. Don't miss glomerular causes - check for dysmorphic RBCs, proteinuria, and RBC casts

The 2025 AUA/SUFU guidelines emphasize shared decision-making regarding follow-up after a negative evaluation, recognizing that most patients with a negative risk-stratified evaluation don't require ongoing monitoring 1.