Treatment of Microcytic Anemia
The first-line treatment for microcytic anemia is oral iron supplementation with ferrous sulfate 200 mg three times daily for at least three months after correction of anemia to replenish iron stores. 1
Diagnostic Approach
- Assess iron parameters (ferritin, transferrin saturation) to differentiate between iron deficiency anemia and other causes of microcytic anemia 1, 2
- Serum ferritin <15 μg/L indicates absent iron stores, while <30 μg/L indicates low body iron stores 1
- A cut-off of 45 μg/L provides optimal sensitivity and specificity for iron deficiency in practice 1
- A low MCV with RDW >14.0% suggests iron deficiency anemia, while a low MCV with RDW ≤14.0% suggests thalassemia minor 1, 3
Treatment Algorithm Based on Etiology
Iron Deficiency Anemia (Most Common Cause)
- Oral iron supplementation with ferrous sulfate 200 mg three times daily (providing approximately 65 mg elemental iron per tablet) 1, 4
- Alternative formulations include ferrous gluconate and ferrous fumarate if ferrous sulfate is not tolerated 1, 5
- Ascorbic acid can be added to enhance iron absorption 1
- Continue treatment for at least three months after correction of anemia to replenish iron stores 1, 4
- A good response is defined as a hemoglobin rise ≥10 g/L within a 2-week timeframe 1
For Non-Responders to Oral Iron
- Consider intravenous (IV) iron if there is malabsorption or if oral iron is not tolerated 1, 6
- IV iron formulations have shown significant increases in hemoglobin, hematocrit, serum ferritin, and transferrin saturation in clinical trials 6
- Expect a hemoglobin increase of at least 2 g/dL within 4 weeks of starting IV iron therapy 1, 6
Genetic Disorders of Iron Metabolism or Heme Synthesis
- For X-linked sideroblastic anemia (ALAS2 defects), initial treatment with pyridoxine (vitamin B6) 50-200 mg daily is recommended 2, 7
- For pyridoxine-responsive cases, continue lifelong supplementation at 10-100 mg daily 2, 7
- For SLC25A38 defects, consider hematopoietic stem cell transplantation (HSCT) as the only curative option 2, 7
- For STEAP3 defects, treatment includes erythrocyte transfusions combined with erythropoietin (EPO) 2, 7
- For SLC11A2 defects, treatment includes oral iron supplementation, EPO, and/or erythrocyte transfusions based on individual needs 1, 2
- For iron-refractory iron deficiency anemia (IRIDA) due to TMPRSS6 defects:
Monitoring and Follow-up
- Monitor hemoglobin concentration and red cell indices at three-monthly intervals for one year and then after a further year 1
- Provide additional oral iron if hemoglobin or MCV falls below normal 1
- For patients receiving multiple transfusions or long-term iron therapy, monitor for iron overload 1, 2
- Consider MRI of the liver in specific cases to detect toxic iron loading early 1, 2
Management of Iron Overload
- Regular monitoring of iron parameters (ferritin, TSAT) and liver enzymes is essential 2, 7
- Phlebotomy is the preferred method for managing iron overload when tolerated 2, 7
- Iron chelation therapy is recommended when phlebotomies are not tolerated 2, 7
Special Considerations
- For patients with Myelodysplastic Syndrome with Ring Sideroblasts (MDS-RS), especially with SF3B1 mutation, luspatercept has shown promising results 7
- Family screening and genetic counseling are important for hereditary forms of microcytic anemia 2, 7
- Avoid overlooking combined deficiencies, such as iron deficiency coexisting with B12 or folate deficiency 1
Common Pitfalls and Caveats
- Failing to identify the underlying cause of iron deficiency, particularly gastrointestinal bleeding in adults 4, 9
- Overlooking genetic disorders in patients with refractory anemia despite adequate iron supplementation 8
- Not continuing iron therapy long enough to replenish iron stores after hemoglobin normalization 1, 4
- Misdiagnosing thalassemia as iron deficiency anemia, leading to unnecessary iron therapy 1, 3
- Not monitoring for iron overload in patients receiving multiple transfusions or long-term iron therapy 1, 2