What is the best explanation for a low red blood cell (RBC) count with a normal hemoglobin (Hb) level in a patient with anemia?

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Discrepancy Between Low RBC Count and Normal Hemoglobin in Anemia

The most likely explanation for a female patient with anemia having a low RBC count (2.70 x 10^6/μL) but normal hemoglobin (14.5 g/dL) is rouleaux formation (option D).

Understanding the Discrepancy

When analyzing these laboratory values, several key observations can be made:

  • The patient has a significantly low RBC count (2.70 x 10^6/μL), which would typically suggest anemia
  • The hemoglobin level (14.5 g/dL) is normal or even slightly elevated for a female patient
  • All quality control measures are reported as acceptable

Why Rouleaux Formation Explains This Pattern

Rouleaux formation occurs when RBCs stack together like coins, causing automated analyzers to count these stacks as single cells, resulting in:

  1. Falsely decreased RBC count (as multiple cells are counted as one)
  2. Normal or even elevated hemoglobin (as the total hemoglobin content is still accurately measured)

This creates the paradoxical finding of "anemia" by RBC count with normal hemoglobin levels 1.

Ruling Out Other Options

A. Technologist Error

  • With acceptable quality control, systematic technologist error is unlikely
  • The specific pattern of low RBC with normal Hb is consistent with a known analytical interference rather than random error

B. Lipemia

  • While lipemia can interfere with some laboratory measurements, it typically affects multiple parameters and doesn't create this specific pattern of low RBC with normal Hb
  • Lipemia more commonly affects chemistry tests rather than causing this specific hematological pattern

C. High Anticoagulant to Blood Ratio

  • Excess anticoagulant would dilute the sample, causing both RBC count and hemoglobin to be proportionally decreased
  • This would not explain the discrepancy between these two parameters 2

Clinical Significance of Rouleaux Formation

Rouleaux formation is often associated with:

  • Plasma cell disorders (multiple myeloma, Waldenström's macroglobulinemia)
  • Inflammatory conditions with elevated fibrinogen or globulins
  • Paraproteinemias
  • Some autoimmune disorders

The presence of rouleaux can be confirmed by examining a peripheral blood smear, which would show the characteristic stacking of RBCs 2.

Laboratory Implications

When rouleaux formation is suspected:

  • Request a peripheral blood smear examination to confirm
  • Consider additional testing for conditions associated with rouleaux formation
  • Interpret automated CBC results with caution
  • Consider diluting the sample to break up the rouleaux and obtain more accurate cell counts

Conclusion

The discrepancy between the low RBC count and normal hemoglobin level in this anemic patient is best explained by rouleaux formation (option D), which creates a falsely low RBC count while hemoglobin measurement remains accurate. This finding should prompt further investigation for underlying conditions that cause increased plasma proteins and rouleaux formation.

References

Guideline

Diagnosis and Management of Anemia and Polycythemia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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