What does an elevated Red Cell Distribution Width (RDW) indicate?

Elevated Red Cell Distribution Width (RDW): Clinical Significance and Diagnostic Approach

An elevated Red Cell Distribution Width (RDW) indicates increased variability in red blood cell size (anisocytosis) and serves as an important marker for various underlying conditions including nutritional deficiencies, inflammatory disorders, and hematologic abnormalities that warrant further investigation. 1

Understanding RDW Values

• RDW is calculated by dividing the standard deviation of red blood cell volume by Mean Corpuscular Volume (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% considered elevated 1
• Elevated RDW reflects heterogeneity in red blood cell size, which can result from various pathophysiological processes 1, 2

Common Causes of Isolated RDW Elevation

Nutritional Deficiencies

• Iron deficiency (even in early stages before anemia develops) 1
• Vitamin B12 or folate deficiency 1
• Vitamin D deficiency (studies show an inverse relationship between 25OHD levels and RDW) 3

Inflammatory Conditions

• Chronic and acute inflammatory states can impair erythropoiesis and increase RDW 2
• Inflammatory cytokines affect bone marrow function and red blood cell production 4
• COVID-19 and other infectious conditions can elevate RDW through erythrocyte membrane injury 1

Hematologic Disorders

• Early iron deficiency anemia (may present with elevated RDW before MCV decreases) 1
• Mixed anemias (where more than one mechanism is present) 1
• Hemolytic conditions (affecting red blood cell survival) 2

Diagnostic Approach to Elevated RDW

Initial Evaluation

• Complete blood count with review of other red cell indices, particularly MCV 1
• Reticulocyte count to assess bone marrow response 1
• Inflammatory markers including CRP 1

Based on MCV Results:

• Normal MCV with elevated RDW:

  • Consider early iron deficiency, early B12/folate deficiency, or mixed nutritional deficiencies 1
  • May indicate concurrent microcytosis and macrocytosis averaging to normal MCV 1

• Low MCV (microcytosis) with elevated RDW:

  • Strongly suggests iron deficiency anemia 1
  • Can help differentiate from thalassemia minor, which classically presents with microcytosis but normal or only mildly elevated RDW (though this distinction is not absolute) 1, 5

• High MCV (macrocytosis) with elevated RDW:

  • Suggests vitamin B12 or folate deficiency 1
  • Consider alcohol use, liver disease, or myelodysplastic syndrome 2

Recommended Additional Testing

• Serum ferritin (< 30 μg/L without inflammation, < 100 μg/L with inflammation suggests iron deficiency) 1
• Transferrin saturation to assess iron status 1
• Vitamin B12 and folate levels if macrocytosis is present 1
• Consider vitamin D levels, particularly in patients with chronic conditions 3

Clinical Significance and Prognostic Value

• Elevated RDW has been associated with increased mortality in various conditions 2
• In cardiovascular disease, elevated RDW correlates with poorer outcomes 4
• In critically ill patients, elevated RDW is associated with decreased ventilator-free days 6
• RDW may reflect underlying oxidative stress and systemic inflammation 4, 2

Important Caveats

• RDW values can vary between laboratory instruments, so interpret according to the specific laboratory's reference range 1
• Even with normal RDW, if anemia is present, a complete workup is still warranted 1
• An isolated elevated RDW without anemia should not be dismissed and may represent early stages of nutritional deficiencies 1, 2
• Almost half of thalassemia cases may present with elevated RDW, limiting its specificity in differentiating from iron deficiency 5