What is the significance of Red Cell Distribution Width (RDW) in a patient with microcytic anemia?

What is RDW (Red Cell Distribution Width)?

RDW is a laboratory measurement that quantifies the variation in size of circulating red blood cells, calculated by dividing the standard deviation of red blood cell volume by the mean corpuscular volume (MCV) and multiplying by 100 to express as a percentage. 1

Technical Definition and Calculation

• RDW-CV (coefficient of variation) is the primary clinical tool, calculated using the formula: RDW (%) = {SD of red blood cell volume (fL)/MCV (fL)} × 100 1
• Normal RDW range is typically 11.0-14.0%, with values ≤14.0% considered normal (representing the 95th percentile in reference populations) 1
• RDW-SD represents the absolute standard deviation of red blood cell volumes measured in femtoliters, providing direct measurement without normalization to MCV 1

Critical Clinical Significance in Microcytic Anemia

The combination of low MCV and elevated RDW (>14-16.9%) is pathognomonic for iron deficiency anemia, mandating immediate serum ferritin testing and comprehensive gastrointestinal evaluation in adult men and post-menopausal women to exclude malignancy. 2

Distinguishing Iron Deficiency from Thalassemia Trait

• High RDW (>14.0%) with low MCV strongly indicates iron deficiency anemia, reflecting heterogeneous red cell populations as iron stores become progressively depleted 2, 3
• Normal or mildly elevated RDW with low MCV suggests thalassemia minor, which typically presents with more uniform red cell size 2, 1
• The elevated RDW in iron deficiency reflects the presence of both older normal-sized cells and newer microcytic cells being produced under iron-deficient conditions 3

Important caveat: While this distinction is useful, research shows that almost half of thalassemia cases may also present with increased RDW, limiting its specificity 4, 5. Therefore, sequential evaluation including iron studies and hemoglobin analysis remains essential 4.

Diagnostic Algorithm When RDW is Elevated

When RDW >14.0% is detected, follow this algorithmic approach:

Step 1: Assess MCV Pattern

• Low MCV + High RDW → Iron deficiency anemia (most likely) 2, 1
• Normal MCV + High RDW → Early iron deficiency, vitamin B12/folate deficiency, or hemolysis 1
• Normal MCV + High RDW with normal hemoglobin → Consider combined deficiency (iron plus folate or B12) 2

Step 2: Confirm with Iron Studies

• Measure serum ferritin immediately (the single most powerful test) 2, 3
  • Ferritin <30 μg/L confirms iron deficiency in absence of inflammation 2, 1
  • Ferritin <100 μg/L may indicate iron deficiency if concurrent inflammation, malignancy, or hepatic disease present 2, 1
• Measure transferrin saturation (<30% supports iron deficiency) 2
• Measure C-reactive protein (CRP) to interpret ferritin correctly in context of inflammation 2, 3

Step 3: Investigate Source in High-Risk Populations

• All adult men and post-menopausal women with confirmed iron deficiency require complete gastrointestinal evaluation, regardless of symptom presence or severity 2
• Upper endoscopy with mandatory small bowel biopsies to exclude malignancy and detect coeliac disease (present in 2-3% of IDA patients) 2
• Colonoscopy or CT colonography to exclude colonic cancer/polyps 2

Additional Clinical Contexts for Elevated RDW

Beyond microcytic anemia, elevated RDW occurs in:

• Inflammatory conditions including acute COVID-19, where erythrocyte membrane injury and reduced deformability occur 1
• Inflammatory bowel disease, helping distinguish iron deficiency from anemia of chronic disease 1
• Cancer patients, particularly lung cancer with platinum-based chemotherapy causing accelerated red cell turnover 1

Treatment Implications

Once iron deficiency is confirmed (ferritin <30 μg/L), initiate oral iron supplementation immediately and continue for 3-6 months after hemoglobin normalizes to replete iron stores. 2

• Recheck CBC in 4-6 weeks to confirm reticulocyte response and declining RDW 3
• Address underlying cause including stopping NSAIDs/anticoagulants when possible 2
• For vitamin deficiencies, provide appropriate B12 or folate supplementation 1

Key Pitfalls to Avoid

• Do not rely on RDW alone to differentiate iron deficiency from thalassemia—sensitivity is only 67.9% and specificity 25% for iron deficiency 5
• Do not ignore normal RDW if clinical suspicion for iron deficiency exists—32% of iron deficiency cases may have normal RDW 5
• Always interpret RDW alongside other parameters including hemoglobin, MCV, ferritin, and transferrin saturation 1
• Consider absolute RDW (RDW-SD) rather than relative RDW (RDW-CV) in discriminant formulas, as this improves diagnostic performance 6