What are the primary causes and treatments of microcytic anemia?

Primary Causes and Treatments of Microcytic Anemia

Iron deficiency anemia is the most common cause of microcytic anemia worldwide, accounting for approximately 80% of cases, followed by anemia of chronic disease, thalassemia, and other rare conditions. 1, 2

Causes of Microcytic Anemia

Microcytic anemia is characterized by small red blood cells with MCV <80 fL, often with hypochromia (low MCHC). The main causes include:

1. Iron Deficiency Anemia

• Most common cause (80% of microcytic anemias)
• Laboratory findings:
  • Low MCV (<80 fL)
  • Low serum ferritin (<15 μg/L)
  • Low transferrin saturation
  • Elevated RDW
  • Low or normal RBC count 1

2. Anemia of Chronic Disease (ACD)

• Associated with inflammatory conditions, cancer, infections
• Laboratory findings:
  • Low or normal MCV
  • Normal or high serum ferritin (>100 μg/L)
  • Low transferrin saturation
  • Normal or slightly elevated RDW 3, 1

3. Thalassemia

• Hereditary disorder of hemoglobin synthesis
• Laboratory findings:
  • Very low MCV
  • Normal ferritin
  • Normal transferrin saturation
  • Normal RDW
  • Normal or elevated RBC count 1

4. Other Rare Causes

• Lead poisoning
• Sideroblastic anemia
• Hemoglobinopathies (HbC, D, E, S) 3, 4

Diagnostic Approach

Laboratory Evaluation

• Complete blood count with MCV, MCHC, and RDW
• Iron studies:
  • Serum ferritin
  • Transferrin saturation
  • Serum iron
  • Total iron binding capacity (TIBC)
• Reticulocyte count
• Inflammatory markers (CRP, ESR) 1

Differential Diagnosis Table

Parameter	Iron Deficiency	Anemia of Chronic Disease	Thalassemia
MCV	Low (<80 fL)	Low or normal	Very low
Serum Ferritin	Low (<15 μg/L)	Normal or high (>100 μg/L)	Normal
Transferrin Saturation	Low	Low	Normal
RDW	Elevated	Normal or slightly elevated	Normal
RBC Count	Low or normal	Low or normal	Normal or elevated
Inflammatory Markers	Normal	Elevated	Normal

Treatment Approaches

1. Iron Deficiency Anemia

• Oral iron supplementation:
  • Ferrous sulfate 200 mg 2-3 times daily
  • Continue for 3 months after hemoglobin normalization to replenish stores
  • Consider adding vitamin C to enhance absorption 1
• Parenteral iron:
  • Consider if oral therapy fails or is not tolerated
  • Useful in cases of malabsorption or when losses exceed oral replacement capacity 1, 5
• Investigate underlying cause:
  • Particularly important in postmenopausal women
  • Consider GI evaluation (endoscopy, colonoscopy) to rule out occult bleeding 1

2. Anemia of Chronic Disease

• Treat underlying condition when possible
• Consider erythropoietin in selected cases
• Intravenous iron may be beneficial in some cases 3, 2

3. Thalassemia

• Treatment depends on severity:
  • Mild forms (traits) usually require no specific treatment
  • Severe forms may require blood transfusions
  • Iron chelation therapy may be necessary for transfusion-dependent patients 6

4. Other Causes

• Treatment directed at specific etiology
• For sideroblastic anemia: pyridoxine (vitamin B6) may help in some cases
• For lead poisoning: chelation therapy 4

Monitoring and Follow-up

• Check hemoglobin and red cell indices after 4-6 weeks of treatment
• Target hemoglobin increase of at least 2 g/dL within 4 weeks 3
• Continue iron therapy for at least 3 months after normalization of hemoglobin
• Target ferritin level of at least 100 ng/mL 1

Common Pitfalls and Caveats

• Ferritin is an acute phase reactant and may be falsely elevated in inflammatory conditions
• Up to 15% of iron-deficient patients may have coexisting B12 deficiency
• Failing to investigate the underlying cause of iron deficiency can lead to missed diagnoses
• Premature discontinuation of iron therapy before replenishing stores can lead to recurrence 1
• Mixed deficiencies (iron and folate/B12) can occur, particularly in malabsorption 3

Special Considerations

• Pregnant women, infants, and elderly are at higher risk for iron deficiency
• Athletes may have increased iron requirements
• Post-bariatric surgery patients often have impaired iron absorption
• Limited blood transfusion may be required for symptomatic severe anemia 1, 2