How should I evaluate and treat a patient with anemia characterized by low hemoglobin and increased red‑cell distribution width?

Evaluation and Management of Low Hemoglobin with Elevated RDW

Begin with a complete blood count including MCV, reticulocyte count, serum ferritin, transferrin saturation, and CRP to determine the specific cause of anemia, as elevated RDW with low hemoglobin most commonly indicates iron deficiency anemia but can also reflect vitamin B12/folate deficiency, hemolysis, or combined deficiencies. 1

Initial Diagnostic Algorithm Based on MCV

Microcytic Anemia (Low MCV) + Elevated RDW

• This pattern strongly suggests iron deficiency anemia and is the most common presentation you will encounter 1, 2
• The elevated RDW reflects heterogeneous red cell populations with varying degrees of microcytosis as iron stores become progressively depleted 3
• Confirm diagnosis with serum ferritin: <30 μg/L without inflammation or <100 μg/L with concurrent inflammation 1, 2
• Check transferrin saturation (<16-20% supports iron deficiency) 1

Normocytic Anemia (Normal MCV) + Elevated RDW

• This pattern suggests early iron deficiency, vitamin B12 or folate deficiency, hemolysis, or critically—combined deficiencies 1, 2
• Combined iron and vitamin B12/folate deficiency produces normocytic anemia because the macrocytic effect masks the microcytic effect, but RDW remains elevated due to the heterogeneous mixture of cell sizes 1
• Simultaneously evaluate both iron status (ferritin, transferrin saturation) AND vitamin B12/folate levels in all patients with this pattern 1
• Check reticulocyte count to assess for hemolysis or acute blood loss 1

Macrocytic Anemia (High MCV) + Elevated RDW

• Suggests vitamin B12 or folate deficiency, though approximately 31% of pernicious anemia patients may have normal RDW 4
• Measure serum B12, folate, and methylmalonic acid if B12 deficiency is suspected 2

Essential Laboratory Workup

Minimum initial testing includes: 1

• Complete blood count with MCV
• Reticulocyte count
• Serum ferritin
• Transferrin saturation
• C-reactive protein (to assess inflammation)

Add based on clinical context:

• Vitamin B12 and folate levels (especially if normocytic or macrocytic) 1
• Hemoglobin electrophoresis if thalassemia suspected (certain ethnic backgrounds with microcytosis) 1, 5
• Peripheral blood smear review 2

Treatment Based on Confirmed Diagnosis

Iron Deficiency Anemia (Most Common)

• Initiate iron supplementation (oral or intravenous) once diagnosis is confirmed 1, 2
• Investigate the source of blood loss, particularly gastrointestinal causes 1, 2
• For adult men and post-menopausal women: perform both upper and lower endoscopy to exclude malignancy, regardless of anemia severity 1, 5
• Monitor RDW serially to assess treatment response 1

Combined Deficiencies

• Replace both nutrients simultaneously when iron deficiency coexists with B12 or folate deficiency 1
• Failure to recognize combined deficiencies leads to incomplete treatment response 1

Vitamin B12 or Folate Deficiency

• Provide appropriate vitamin supplementation based on confirmed deficiency 2

Critical Pitfalls to Avoid

Do not assume iron deficiency based solely on microcytosis without checking RDW, as thalassemia trait typically shows low MCV with normal or only mildly elevated RDW 1, 2

Do not overlook combined deficiencies (iron plus B12/folate), which maintain normal MCV despite significant nutrient deficits but show elevated RDW 1

Do not fail to investigate for gastrointestinal malignancy in adult men and post-menopausal women with confirmed iron deficiency 1, 5

Do not attribute microcytosis to thalassemia in certain ethnic groups without laboratory confirmation via hemoglobin electrophoresis 1, 5

Important Nuances

While elevated RDW is highly suggestive of iron deficiency when combined with microcytosis, research shows that 32% of anemia of chronic disease cases and up to 66% of beta-thalassemia trait cases can also show elevated RDW 6. Additionally, inflammatory conditions including tuberculosis can elevate RDW independent of iron status 7. This is why confirmatory testing with ferritin and transferrin saturation is mandatory before initiating treatment 1, 2.

The degree of RDW elevation correlates inversely with hemoglobin level and transferrin saturation in iron deficiency, potentially reflecting severity of deficiency 3.