How do sickle cells or spherocytes interfere with the erythrocyte sedimentation rate (ESR)?

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How Sickle Cells and Spherocytes Affect Erythrocyte Sedimentation Rate

Sickle cells and spherocytes prevent normal rouleaux formation, causing a falsely decreased erythrocyte sedimentation rate (ESR) (answer C).

Mechanism of ESR and Abnormal Red Cell Impact

The ESR is a common laboratory test that measures how quickly red blood cells settle at the bottom of a test tube over a specific time period. This process depends on several key factors:

Normal Rouleaux Formation

  • In normal conditions, red blood cells tend to stack together like coins (rouleaux formation)
  • This stacking increases the mass-to-surface area ratio, causing faster sedimentation
  • Rouleaux formation is primarily influenced by plasma proteins (especially fibrinogen) and red cell membrane properties

How Sickle Cells Interfere with ESR

  • Sickle cells have abnormal membrane properties due to HbS polymerization that damages the cell membrane and cytoskeleton 1
  • These cellular factors prevent normal rouleaux formation despite having elevated fibrinogen levels 2
  • Studies have demonstrated that patients with sickle cell anemia have abnormally low sedimentation rates due to these cellular factors 2
  • Even when plasma from healthy subjects is substituted, the sedimentation rates remain low, confirming this is a cell-related phenomenon 2

How Spherocytes Affect ESR

  • Spherocytes, like sickle cells, have altered membrane properties that prevent normal stacking
  • Their spherical shape (rather than biconcave) reduces surface contact between cells
  • This altered geometry prevents effective rouleaux formation, resulting in falsely decreased ESR values

Evidence from Research Studies

Research has specifically demonstrated that:

  • Asymptomatic patients with sickle cell anemia have abnormally low sedimentation rates in relation to their hematocrits 2
  • The low sedimentation rate persists even when plasma from healthy control subjects is substituted 2
  • During painful sickle cell crisis, ESR may increase due to changes in both cellular factors and elevated plasma fibrinogen levels 2

Clinical Implications

Understanding how sickle cells and spherocytes affect ESR has important clinical implications:

  • Falsely decreased ESR in patients with sickle cell disease or spherocytosis may mask inflammatory conditions
  • During sickle cell crisis, ESR may normalize or even increase due to changes in red cell properties and plasma factors
  • Clinicians should interpret ESR results with caution in patients with these red cell abnormalities

The primary mechanism by which sickle cells and spherocytes interfere with ESR is through prevention of normal rouleaux formation, leading to falsely decreased values.

References

Guideline

Sickle Cell Disease Pathophysiology

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 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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