How do you manage a patient with microcytosis?

Management of Microcytosis

The management of microcytosis should begin with serum ferritin measurement as the first diagnostic test, followed by a systematic evaluation to determine the underlying cause, with iron deficiency anemia and thalassemia trait being the most common etiologies. 1, 2

Diagnostic Approach

Initial Laboratory Evaluation

• Complete Blood Count (CBC) with hemoglobin measurement
• Serum ferritin (most important initial test)
• Additional tests based on ferritin results:
  • If ferritin is low: Confirm iron deficiency
  • If ferritin is normal/high: Order iron studies (serum iron, total iron-binding capacity, transferrin saturation) and consider hemoglobin electrophoresis 1, 2

Differential Diagnosis Parameters

Use these parameters to differentiate between common causes:

Parameter	Iron Deficiency	Thalassemia Trait	Anemia of Chronic Disease
MCV	Low	Very low (<70 fl)	Low/Normal
RDW	High (>14%)	Normal (≤14%)	Normal/Slightly elevated
Ferritin	Low (<30 μg/L)	Normal	Normal/High
TSAT	Low	Normal	Low
RBC count	Normal/Low	Normal/High	Normal/Low

Management Based on Etiology

1. Iron Deficiency Anemia

• Identify source of blood loss (most common cause in adults is gastrointestinal bleeding)
• Treatment:
  • Oral iron supplementation: Ferrous sulfate 325 mg daily or on alternate days
  • Continue for 3 months after hemoglobin normalizes to replenish iron stores
  • Monitor hemoglobin weekly until stable, then every 2-4 weeks
  • Monitor ferritin and transferrin saturation monthly during initial treatment 1, 2
• Consider IV iron if:
  • No significant improvement after 4-6 weeks of oral therapy
  • Patient cannot tolerate oral iron
  • Malabsorption is present
  • Blood loss exceeds oral replacement capacity 1, 3

2. Thalassemia Trait

• Usually requires no specific treatment
• Genetic counseling may be appropriate
• Avoid unnecessary iron supplementation (could worsen iron overload)
• Patients with beta-thalassemia trait typically have elevated hemoglobin A2 levels 2, 4

3. Anemia of Chronic Disease

• Address the underlying inflammatory condition
• Monitor hemoglobin levels every 2-4 weeks initially
• Consider erythropoiesis-stimulating agents if anemia worsens or becomes symptomatic despite treating the underlying condition 1

4. Other Causes

• Lead toxicity: Chelation therapy if confirmed
• Sideroblastic anemia: Treatment depends on type (acquired vs. inherited)
• Hemoglobinopathies (HbE, HbC, etc.): Management based on specific variant 5, 4

Further Evaluation for Iron Deficiency

If iron deficiency is confirmed, investigate the underlying cause:

• Premenopausal women: Evaluate menstrual blood loss
• Adult men and postmenopausal women: Gastrointestinal evaluation is mandatory to rule out malignancy
• Children and adolescents: Consider dietary factors, malabsorption, or occult blood loss 2, 5

Common Pitfalls to Avoid

• Misinterpreting ferritin levels in the presence of inflammation (ferritin is an acute phase reactant)
• Inadequate duration of iron therapy (continue until iron stores are replenished)
• Overlooking genetic causes of microcytosis
• Failing to investigate the source of blood loss in iron deficiency
• Assuming microcytosis is always due to iron deficiency without proper testing 1, 2

Special Considerations

• In patients with sickle cell trait, microcytosis may be due to co-inherited alpha-thalassemia or iron deficiency 6
• Target parameters for iron supplementation: ferritin >100 ng/mL and TSAT >20% 1
• Pregnant women, infants, and elderly patients are at higher risk for iron deficiency 1