What is the management approach for a patient with microcytosis (small red blood cells), elevated Red Cell Distribution Width (RDW), and normal hemoglobin levels?

Management of Microcytosis with Elevated RDW and Normal Hemoglobin

The patient with microcytosis (MCV 77), low MCH (24), normal MCHC (31), and markedly elevated RDW (56.3) should be evaluated for iron deficiency with serum ferritin testing, even in the absence of anemia, as this presentation strongly suggests iron deficiency requiring investigation for underlying gastrointestinal pathology. 1, 2

Diagnostic Approach

Initial Laboratory Testing

• Serum ferritin: Most specific test for iron deficiency

  • <15 μg/L is diagnostic of iron deficiency (specificity 0.99)
  • <45 μg/L has good specificity (0.92) and may warrant GI investigation 1
  • Values may be falsely normal in inflammatory conditions

• Additional iron studies:

  • Transferrin saturation (<30% suggests iron deficiency)
  • Serum iron and total iron binding capacity 2

Differential Diagnosis

1. Non-anemic iron deficiency (NAID): Most likely diagnosis given the microcytosis and markedly elevated RDW 1

2. Thalassemia trait: Usually presents with:

   • Microcytosis with normal or only mildly elevated RDW
   • Often elevated red cell count
   • Consider hemoglobin electrophoresis if iron studies are normal 1

3. Combined deficiency: The extremely high RDW (56.3) may indicate combined nutritional deficiencies 2

4. Anemia of chronic disease: Can present with microcytosis but typically has less dramatic RDW elevation 1

5. Rare genetic disorders: Consider if standard workup is negative 1

Management Plan

For Confirmed Iron Deficiency

1. Iron supplementation:

   • Oral iron: 100-200 mg elemental iron daily in divided doses 2
   • Monitor response: Expect normalization of RDW and MCV within 4-8 weeks

2. Investigation for underlying cause:

   • Gastrointestinal evaluation is mandatory in adult men and post-menopausal women 1

     • Upper endoscopy with duodenal biopsies (to rule out celiac disease)
     • Colonoscopy (to rule out colorectal cancer/polyps)
     • Consider small bowel evaluation if upper and lower endoscopies are negative

   • Other causes to assess:

     • Medication history (NSAID use)
     • Menstrual blood loss in premenopausal women
     • Dietary assessment for inadequate iron intake

For Thalassemia Trait (if iron studies normal)

• Hemoglobin electrophoresis to confirm diagnosis
• Genetic counseling if confirmed
• No specific treatment required for the carrier state 1

Monitoring and Follow-up

• Repeat CBC in 4-8 weeks to assess response to iron therapy
• If no improvement in RDW and MCV with iron therapy, reconsider diagnosis
• For confirmed iron deficiency, continue iron supplementation for 3-6 months to replenish stores 2

Important Considerations

• The extremely high RDW (56.3) is unusual even for typical iron deficiency and suggests severe, longstanding deficiency 2
• Do not assume thalassemia without appropriate testing, even in patients from high-risk ethnic groups 2
• Non-anemic iron deficiency should not be dismissed as clinically insignificant, particularly in men and post-menopausal women where GI malignancy must be excluded 1
• The combination of microcytosis with markedly elevated RDW is highly characteristic of iron deficiency, whereas thalassemia typically presents with more homogeneous red cell population (normal or mildly elevated RDW) 2, 3