What is the clinical significance of Red Cell Distribution Width (RDW)?

Clinical Significance of Red Cell Distribution Width (RDW)

RDW is a valuable hematological parameter that provides significant clinical information beyond anemia classification, serving as both a diagnostic tool and a prognostic marker for various conditions. 1

Definition and Normal Values

• RDW is calculated by dividing the standard deviation of red blood cell volume by MCV and multiplying by 100 to express the result as a percentage 1
• Normal RDW is generally considered to be between 11.0-14.0%, with values above 14.0% corresponding to the 95th percentile in reference populations 1
• RDW reflects the degree of heterogeneity in erythrocyte volume (anisocytosis) 2

Diagnostic Applications

Anemia Differential Diagnosis

• When combined with MCV, RDW helps distinguish between different types of anemias 1:
  • Iron deficiency anemia: Low MCV with elevated RDW (>14.0%) 1, 3
  • Thalassemia minor: Low MCV with normal or only mildly elevated RDW 1
  • Early iron deficiency: Normal MCV with elevated RDW 1
  • Vitamin B12 or folate deficiency: High MCV with elevated RDW 3

Important Diagnostic Considerations

• A normal RDW with microcytosis (low MCV) suggests thalassemia trait rather than iron deficiency 1
• A wide size range of red cells (high RDW) can help identify iron deficiency when microcytosis and macrocytosis co-exist, resulting in a normal MCV 1
• RDW should always be interpreted alongside other hematologic parameters including hemoglobin, MCV, and other red cell indices 1

Prognostic Value

• Elevated RDW has been associated with increased mortality risk in the general population 2
• RDW elevation is observed in various conditions beyond anemia, including 2:
  • Cardiovascular diseases 4
  • Venous thromboembolism 2
  • Cancer 2
  • Diabetes 2
  • Respiratory conditions (pneumonia, COPD) 2
  • Liver and kidney failure 2
  • Inflammatory conditions, including COVID-19 1

Recommended Workup for Abnormal RDW

• Minimum workup for elevated RDW should include 1, 3:
  • Complete blood count with MCV
  • Reticulocyte count
  • Serum ferritin
  • Transferrin saturation
  • CRP (to assess for inflammation)
• If iron deficiency is suspected, confirmation with serum ferritin (<30 μg/L in absence of inflammation, <100 μg/L with inflammation) is recommended 3

Common Pitfalls and Limitations

• Assuming iron deficiency based solely on microcytosis without checking RDW 3
• Relying exclusively on RDW to differentiate thalassemia from iron deficiency, as studies show up to half of thalassemia cases may have elevated RDW 5, 6
• Failing to investigate for gastrointestinal malignancy in adult men and post-menopausal women with iron deficiency anemia 3
• Overlooking the possibility of combined deficiencies (e.g., iron and B12), which may result in a normal MCV despite abnormal RDW 3
• RDW values can vary between different laboratory instruments, so values should be interpreted according to the specific laboratory's reference range 1

Underlying Mechanisms of Elevated RDW

• Increased RDW reflects deregulation of erythrocyte homeostasis involving 2:
  • Impaired erythropoiesis
  • Abnormal red blood cell survival
  • Oxidative stress
  • Inflammation
  • Poor nutritional status
  • Erythrocyte fragmentation
  • Alteration of erythropoietin function