Hereditary Spherocytosis Can Cause a Falsely Normal or Decreased ESR
The correct answer is C. Hereditary spherocytosis. Hereditary spherocytosis can cause falsely normal or decreased erythrocyte sedimentation rate (ESR) due to the altered shape and decreased deformability of red blood cells.
Mechanism of ESR and How Hereditary Spherocytosis Affects It
ESR measures the rate at which red blood cells (RBCs) settle in a tube of anticoagulated blood over a specific time period. The test depends on:
- RBC shape and deformability
- RBC surface charge
- Plasma protein composition
In hereditary spherocytosis:
- RBCs have reduced membrane surface area and increased sphericity 1
- These spherical RBCs have decreased ability to aggregate into rouleaux formations
- The decreased rouleaux formation prevents normal sedimentation
- This results in falsely normal or decreased ESR values despite potential underlying inflammation
Why Other Options Are Incorrect
Multiple myeloma (Option A) - Multiple myeloma typically causes an elevated ESR due to increased production of immunoglobulins and plasma proteins that enhance rouleaux formation 2.
Hyperfibrinogenemia (Option B) - Increased fibrinogen levels promote rouleaux formation and lead to an elevated ESR, not a decreased one 2.
Rheumatoid arthritis (Option D) - Rheumatoid arthritis is characterized by systemic inflammation that typically causes an elevated ESR due to increased acute phase reactants 2.
Characteristics of Hereditary Spherocytosis
Hereditary spherocytosis is characterized by:
- Genetic defects in red cell membrane proteins (spectrin, ankyrin, band 3, or protein 4.2)
- Band 3 deficiency occurs in approximately 23% of cases 3
- Spectrin deficiency correlates with decreased membrane mechanical stability 1
- Reduced surface area-to-volume ratio of RBCs
- Increased osmotic fragility
- Increased autohemolysis 4
Even "silent" forms of hereditary spherocytosis that present with minimal clinical symptoms can affect ESR measurements 4. These silent forms may have:
- Normal hemoglobin levels
- Normal RBC counts
- Normal or slightly elevated reticulocyte counts
- Decreased osmotic resistance of RBCs
Clinical Relevance
Understanding conditions that can falsely decrease ESR is important because:
- ESR is commonly used to assess inflammation in various conditions
- A falsely normal or decreased ESR in a patient with hereditary spherocytosis might mask underlying inflammatory conditions
- When interpreting ESR in patients with known or suspected hereditary spherocytosis, clinicians should consider using alternative inflammatory markers like CRP, which is not affected by RBC morphology 5
The American College of Cardiology recommends ordering high-sensitivity CRP as the primary test for detecting inflammation due to its higher sensitivity and specificity compared to ESR, particularly in cases where RBC morphology might affect ESR results 5.