What are the causes and management of an increased Red Cell Distribution Width (RDW)?

Causes and Management of Increased Red Cell Distribution Width (RDW)

An elevated Red Cell Distribution Width (RDW) is primarily associated with iron deficiency anemia, vitamin deficiencies, hemolysis, inflammatory conditions, and various chronic diseases, requiring targeted diagnostic workup and treatment of the underlying cause. 1, 2

Common Causes of Increased RDW

• Elevated RDW indicates heterogeneity in red blood cell size (anisocytosis) and is commonly seen in:
  • Iron deficiency anemia (particularly with low MCV) 1, 2
  • Early iron deficiency (may have normal MCV) 1
  • Vitamin B12 or folate deficiency 1, 2
  • Hemolytic conditions 3
  • Inflammatory disorders including COVID-19 1
  • Cardiovascular diseases 4, 5
  • Liver and kidney failure 4
  • Cancer 4
  • Chronic obstructive pulmonary disease 4
  • Polycythemia vera (during active disease) 6

Diagnostic Approach

• Minimum workup for elevated RDW should include:

  • Complete blood count with MCV 1, 2
  • Reticulocyte count 1, 2
  • Serum ferritin 1, 2
  • Transferrin saturation 1, 2
  • C-reactive protein (CRP) 1, 2

• Interpretation based on MCV:

  • Microcytic anemia (low MCV) + high RDW: strongly suggests iron deficiency anemia 1, 2
  • Normocytic anemia (normal MCV) + high RDW: may indicate early iron deficiency, vitamin B12/folate deficiency, or hemolysis 1
  • Macrocytic anemia (high MCV) + high RDW: suggests vitamin B12 or folate deficiency 7

Management Strategy

• For iron deficiency anemia:

  • Confirm diagnosis with serum ferritin (<30 μg/L without inflammation, <100 μg/L with inflammation) 2
  • Initiate iron supplementation (oral or intravenous) 2
  • Investigate potential sources of blood loss, particularly gastrointestinal causes 2
  • For adult men and post-menopausal women, perform both upper and lower gastrointestinal endoscopy to exclude malignancy 2

• For vitamin deficiencies:

  • Provide appropriate vitamin supplementation (B12, folate) 1
  • Investigate underlying cause of deficiency 7

• For inflammatory conditions:

  • Address the underlying inflammatory disorder 1
  • Monitor RDW as a potential marker of disease activity 4

Important Clinical Considerations

• RDW is an inexpensive and readily available parameter that provides valuable diagnostic and prognostic information 3, 4
• Serial monitoring of RDW may help assess response to treatment 2
• An elevated RDW has been identified as an independent risk factor for mortality in various conditions 4, 5
• RDW values can vary between laboratory instruments, so interpret according to the specific laboratory's reference range 1

Common Pitfalls to Avoid

• Assuming iron deficiency based solely on microcytosis without checking RDW 2
• Failing to investigate for gastrointestinal malignancy in adult men and post-menopausal women with iron deficiency anemia 2
• Overlooking the possibility of combined deficiencies (e.g., iron and B12), which may result in a normal MCV despite abnormal RDW 2
• Assuming all cases of vitamin B12 deficiency have elevated RDW (approximately 31% may have normal RDW values) 7
• Attributing microcytosis to thalassemia in certain ethnic groups without laboratory confirmation 2