How can a urine analysis be negative for Red Blood Cells (RBCs) but still show a significant presence of blood?

Discrepancy Between Negative RBC Count and Positive Blood Detection in Urinalysis

A urinalysis can show positive for blood on dipstick testing while being negative for RBCs on microscopic examination due to hemoglobinuria or myoglobinuria, which requires critical distinction to guide proper diagnostic workup. 1

Mechanisms Explaining This Discrepancy

The American Urological Association (AUA) guidelines emphasize that urinalysis with microscopic examination is crucial to distinguish between three distinct conditions that can cause a positive blood result on dipstick testing:

1. True Hematuria: Intact red blood cells in urine
2. Hemoglobinuria: Free hemoglobin in urine without intact RBCs
3. Myoglobinuria: Myoglobin in urine from muscle breakdown 1

How This Happens

• Hemolysis of RBCs: When RBCs lyse or rupture before or during urinalysis, they release free hemoglobin that reacts with the dipstick test while no intact cells remain for microscopic detection 1
• Sensitivity Differences: Dipstick tests can detect hemoglobin at concentrations equivalent to as few as 5-10 RBCs/HPF, making them more sensitive than microscopic examination 2
• Sample Handling: Delayed examination, improper storage, or exposure to temperature extremes can cause RBC lysis 1

Clinical Implications

This discrepancy has important diagnostic implications:

• False Positive Dipstick: The reagent strip test for blood has high sensitivity (94%) but very low specificity (6%), meaning it often detects blood when no clinically significant pathology exists 2
• Diagnostic Accuracy: Microscopic examination helps differentiate true hematuria from hemoglobinuria/myoglobinuria, guiding appropriate further testing 1

Common Causes of Hemoglobinuria Without RBCs

• Intravascular Hemolysis: Hemolytic anemias, transfusion reactions
• Rhabdomyolysis: Muscle injury releasing myoglobin
• Trauma: Including catheter-related trauma 1
• Hemolytic Conditions: Certain medications, toxins, or genetic disorders

Proper Evaluation Approach

1. Confirm with Repeat Testing: Verify findings with properly collected specimens
2. Additional Laboratory Tests: Complete blood count, renal function, liver function, and coagulation studies 1
3. Imaging and Cystoscopy: Based on risk stratification:
   • CT urography (92% sensitivity, 93% specificity) for detecting stones and malignancies
   • Ultrasound (50% sensitivity, 95% specificity) as an alternative 1, 2

Important Considerations

• Risk Stratification: Age and RBC count are significant predictors of genitourinary cancer 2
• Dysmorphic RBCs: Assessment of RBC shape can help differentiate glomerular from non-glomerular bleeding sources 3
• False Negatives: Microscopic examination alone may miss significant pathology; combined testing (dipstick and microscopy) is recommended 4

Common Pitfalls to Avoid

• Assuming Benign Cause: Never assume catheter trauma alone is the source of hematuria without proper investigation 1
• Overlooking Hemolysis: Failure to recognize hemolysis can lead to missed diagnoses of systemic conditions
• Inadequate Follow-up: Patients with unexplained positive dipstick for blood require appropriate evaluation even with negative microscopy 1
• Improper Sample Handling: Examine urine samples promptly to prevent RBC lysis that can cause this discrepancy

By understanding these mechanisms, clinicians can appropriately interpret urinalysis results and determine the necessary follow-up investigations based on the patient's risk factors and clinical presentation.