What are the causes and treatments of microcytic anemia?

Causes of Microcytic Anemia

The main causes of microcytic anemia are iron deficiency anemia, anemia of chronic disease, thalassemias, and sideroblastic anemia, with iron deficiency being the most common cause worldwide (approximately 80%). 1, 2

Common Causes of Microcytic Anemia

1. Iron Deficiency Anemia

• Most common cause globally (80% of all anemias) 3
• Characterized by:
  • Low ferritin (<30 μg/L without inflammation, <100 μg/L with inflammation)
  • Low transferrin saturation (<16%)
  • High TIBC
  • Elevated RDW 1
• Common in:
  • Infants and toddlers
  • Premenopausal or pregnant women
  • Elderly individuals 3
• Etiologies:
  • Menstruation
  • Pregnancy
  • Gastrointestinal bleeding
  • Malabsorption 2

2. Anemia of Chronic Disease (ACD)

• Second most common cause of microcytic anemia 3
• Laboratory findings:
  • Ferritin >100 μg/L
  • Low transferrin saturation (<20%)
  • Low/normal TIBC 1
• Results from functional iron deficiency due to inflammatory processes
• Common in hospitalized patients and the elderly 3

3. Thalassemias

• Genetic disorders affecting globin chain synthesis
• Features:
  • Particularly low MCV despite absence of systemic iron deficiency
  • Normal or elevated ferritin
  • Can range from mild to transfusion-dependent 4, 5

4. Sideroblastic Anemia

• Characterized by ring sideroblasts in bone marrow
• Can be:
  • Congenital (genetic disorders affecting heme synthesis)
  • Acquired (medications, alcohol, lead poisoning)
• May present with both microcytic and normocytic features 1, 4

Genetic Causes of Microcytic Anemia

1. Iron-Refractory Iron Deficiency Anemia (IRIDA)

• Autosomal recessive disorder
• Caused by TMPRSS6 mutations
• Features:
  • Microcytic anemia (less severe with age)
  • Low transferrin saturation
  • Low-to-normal ferritin
  • Poor response to oral iron 6

2. Congenital Erythropoietic Porphyria (CEP)

• Can present as microcytic hypochromic hemolytic anemia
• Associated with:
  • UROS gene mutations (autosomal recessive)
  • GATA1 mutations (X-linked)
• Additional features:
  • Photosensitivity
  • Hemolysis 6

Diagnostic Approach

1. Initial Laboratory Evaluation:

   • Complete blood count with MCV (<80 μm³ indicates microcytosis)
   • Peripheral blood smear
   • Complete iron studies (ferritin, transferrin saturation, TIBC)
   • Inflammatory markers (CRP) 1

2. Differential Diagnosis Algorithm:

   • Low ferritin (<30 μg/L) → Iron deficiency anemia
   • High ferritin (>100 μg/L) with low transferrin saturation → Anemia of chronic disease
   • Very low MCV with normal/high ferritin → Consider thalassemia
   • Poor response to iron therapy → Consider sideroblastic anemia or IRIDA 6, 1

3. Advanced Testing (when initial evaluation is inconclusive):

   • Bone marrow examination (gold standard for iron deficiency)
   • Hemoglobin electrophoresis (for thalassemias)
   • Genetic testing for hereditary disorders
   • Evaluation for porphyrias if photosensitivity present 6, 2

Common Pitfalls and Caveats

• Misinterpreting ferritin levels: Ferritin is an acute phase reactant and may be elevated despite iron deficiency in inflammatory states 1
• Overlooking combined deficiencies: Iron deficiency can coexist with other causes of anemia
• Inappropriate iron therapy: Can be harmful in conditions like sideroblastic anemia or thalassemia 7
• Failure to identify underlying cause: Especially important in iron deficiency anemia, where the source of blood loss must be identified 2
• Not considering genetic causes: Disorders like IRIDA and sideroblastic anemia require specific management approaches 1

By systematically evaluating patients with microcytic anemia using this approach, clinicians can accurately diagnose the underlying cause and implement appropriate treatment strategies to improve outcomes.