What is the treatment for microcytic anemia?

Treatment of Microcytic Anemia

For iron deficiency anemia (the most common cause), start ferrous sulfate 200 mg three times daily, providing approximately 65 mg elemental iron per dose, and continue for at least three months after hemoglobin normalizes to replenish iron stores. 1

Diagnostic Differentiation Before Treatment

The etiology determines treatment approach, so proper diagnosis is essential:

• Serum ferritin <45 μg/L indicates iron deficiency with optimal sensitivity and specificity, though <15 μg/L confirms absent iron stores and <30 μg/L indicates low body iron stores 1, 2
• Low MCV with RDW >14.0% suggests iron deficiency anemia, while low MCV with RDW ≤14.0% suggests thalassemia minor 1, 2
• Transferrin saturation provides additional confirmation when ferritin is equivocal 2

Treatment Algorithm by Etiology

Iron Deficiency Anemia (Most Common)

First-line oral iron therapy:

• Ferrous sulfate 200 mg (65 mg elemental iron) three times daily 1, 3
• Alternative formulations if not tolerated: ferrous gluconate or ferrous fumarate 2
• Add ascorbic acid to enhance absorption 1, 2
• Continue treatment for at least 3 months after anemia correction to replenish stores 1, 2

Expected response:

• Hemoglobin should rise ≥10 g/L within 2 weeks, confirming iron deficiency 1, 2
• Hemoglobin should increase at least 2 g/dL within 4 weeks 2

For non-responders or intolerance:

• Consider intravenous iron if malabsorption present 2
• Evaluate for genetic disorders of iron metabolism (IRIDA due to TMPRSS6 defects) 1, 2
• Test for thalassemia if RDW is normal or near-normal 2

Iron-Refractory Iron Deficiency Anemia (IRIDA)

• Start with oral iron or oral iron combined with ascorbic acid 1
• Monitor serum ferritin closely—should not exceed 500 μg/L to avoid iron overload toxicity 1, 4
• Consider intravenous iron (iron sucrose or ferric gluconate) for severe TMPRSS6 defects, though complete normalization is rarely achieved 2

X-Linked Sideroblastic Anemia (ALAS2 Defects)

• Initial pyridoxine (vitamin B6) 50-200 mg daily 4, 2
• For responders: lifelong supplementation at 10-100 mg daily to avoid neurotoxicity from excessive doses 4, 2
• Monitor regularly for iron overload 4

Other Genetic Causes

SLC25A38 defects:

• Hematopoietic stem cell transplantation (HSCT) is the only curative option 4, 2
• Symptomatic treatment: erythrocyte transfusions and iron chelation therapy 4, 2

STEAP3 defects:

• Erythrocyte transfusions combined with erythropoietin (EPO) 4, 2
• Monitor and treat systemic iron loading with chelation therapy 4

SLC11A2 defects:

• Oral iron supplementation, EPO, and/or erythrocyte transfusions based on individual needs 4, 2
• Consider MRI of liver to assess iron loading, as normal serum ferritin doesn't exclude liver iron loading 4, 2

Myelodysplastic Syndrome with Ring Sideroblasts (MDS-RS)

• Luspatercept shows promising results, especially with SF3B1 mutation 1, 4

Monitoring and Follow-Up

During treatment:

• Monitor hemoglobin and red cell indices at 3-month intervals for one year, then after another year 2
• Check serum ferritin and transferrin saturation to assess iron store repletion 2
• Provide additional oral iron if hemoglobin or MCV falls below normal 2

For iron overload risk (transfusion-dependent or genetic disorders):

• Regular monitoring of ferritin, transferrin saturation, and liver enzymes 1, 4
• Phlebotomy is preferred for managing iron overload when tolerated 1, 4
• Iron chelation therapy when phlebotomy not tolerated 1, 4
• Consider MRI of liver in specific cases to detect toxic iron loading early 4, 2

Critical Pitfalls to Avoid

• Do not overlook combined deficiencies—iron deficiency can coexist with B12 or folate deficiency 1, 2
• Family screening and genetic counseling are essential for hereditary forms 1, 4
• Do not assume all microcytic anemia is iron deficiency—thalassemia and genetic disorders require different management 2
• In genetic disorders with iron metabolism defects, excessive iron supplementation can cause toxicity 1, 4