What are the types of microcytic anemia and their treatments?

Types of Microcytic Anemia and Their Treatments

Microcytic anemia is primarily caused by iron deficiency, thalassemias, anemia of chronic disease, and genetic disorders affecting iron metabolism or heme synthesis. Understanding the specific type is crucial for appropriate treatment and management of potential complications.

Classification of Microcytic Anemias

1. Iron Deficiency Anemia (IDA)

• Causes: Blood loss (GI bleeding, menstruation), malabsorption, inadequate intake
• Laboratory findings: Low serum ferritin (<30 μg/L without inflammation, <100 μg/L with inflammation), low transferrin saturation (<15%), high TIBC 1
• Treatment:
  • Oral iron supplementation (first-line)
  • IV iron for malabsorption or intolerance to oral therapy
  • Identify and treat underlying cause (e.g., GI bleeding, malabsorption) 2

2. Thalassemias

• Causes: Genetic defects in globin chain synthesis
• Laboratory findings: Normal or elevated ferritin, normal iron studies, abnormal hemoglobin electrophoresis
• Treatment:
  • Mild forms (trait): No specific treatment needed
  • Severe forms: Regular blood transfusions and iron chelation therapy 1, 3

3. Anemia of Chronic Disease (ACD)

• Causes: Chronic inflammation, infection, malignancy
• Laboratory findings: Normal/high ferritin, low transferrin saturation, normal/low TIBC
• Treatment:
  • Treat underlying condition
  • Iron supplementation if concurrent iron deficiency exists
  • Consider erythropoiesis-stimulating agents in selected cases 1

4. Genetic Disorders of Iron Metabolism or Heme Synthesis

a. Sideroblastic Anemias

• Causes: Defects in genes involved in heme synthesis (ALAS2, SLC25A38, GLRX5, STEAP3)
• Laboratory findings: Ring sideroblasts in bone marrow, iron overload
• Treatment:
  • X-linked sideroblastic anemia (XLSA): Pyridoxine 50-200 mg daily (lifelong)
  • Iron chelation therapy for iron overload
  • HSCT for severe cases (especially SLC25A38 defects) 1

b. Iron-Refractory Iron Deficiency Anemia (IRIDA)

• Causes: TMPRSS6 gene mutations
• Laboratory findings: Microcytic anemia unresponsive to oral iron, low TSAT, low-normal ferritin
• Treatment: IV iron supplementation 1

c. Other Rare Genetic Disorders

• DMT1 deficiency (SLC11A2): Oral iron, EPO, transfusions
• Aceruloplasminemia: Iron chelation
• Atransferrinemia (TF gene): Plasma infusions, iron chelation
• ABCB7 defects: No specific treatment for mild anemia 1, 3

Diagnostic Approach

1. Initial Assessment:

   • Complete blood count with MCV, reticulocyte count
   • Serum ferritin, transferrin saturation, CRP (to assess inflammation)

2. Further Workup Based on Initial Results:

   • Low ferritin + low TSAT → Iron deficiency anemia
   • Normal/high ferritin + low TSAT + elevated inflammatory markers → Anemia of chronic disease
   • Normal/high ferritin + normal/high TSAT + family history → Consider thalassemia (hemoglobin electrophoresis)
   • Refractory to iron therapy → Consider genetic disorders 1

3. Special Considerations:

   • Presence of ring sideroblasts → Sideroblastic anemia
   • Photosensitivity + anemia → Consider erythropoietic protoporphyria or congenital erythropoietic porphyria
   • Ataxia + anemia → Consider ABCB7 defect 1

Clinical Pearls

• Reticulocyte count helps distinguish between decreased production (low reticulocytes) and increased destruction/loss (high reticulocytes) of RBCs 1
• In inflammatory conditions, ferritin can be falsely elevated despite iron deficiency 1
• Combined deficiencies (e.g., iron deficiency with B12/folate deficiency) can result in a normocytic picture despite underlying microcytic process 1
• Iron overload can be more harmful than anemia in certain genetic disorders like sideroblastic anemia 1
• Family screening is recommended for genetic causes of microcytic anemia 1

By systematically evaluating patients with microcytic anemia and understanding the underlying pathophysiology, appropriate treatment strategies can be implemented to address both the anemia and any potential complications.