What is the treatment for microcytosis?

Treatment of Microcytosis

The treatment of microcytosis depends entirely on identifying and treating the underlying cause—first exclude iron deficiency with serum ferritin testing, then investigate for thalassemia, anemia of chronic disease, or genetic disorders of iron metabolism. 1, 2

Initial Diagnostic Workup

Serum ferritin is the most powerful and specific test for iron deficiency and should be the first laboratory test ordered when evaluating microcytosis. 1, 2

• Ferritin <30 μg/L confirms iron deficiency and warrants treatment with oral iron supplementation 2
• Ferritin 30-100 μg/L in the presence of inflammation may still indicate iron deficiency, as ferritin is an acute phase reactant that can be falsely elevated 1, 2
• Ferritin >100 μg/L essentially excludes iron deficiency as the cause of microcytosis 1

Red cell distribution width (RDW) helps differentiate causes: elevated RDW (>14.0%) suggests iron deficiency, while normal RDW points toward thalassemia trait. 2, 3

Treatment Based on Etiology

Iron Deficiency Anemia (Most Common Cause)

First-line treatment is oral ferrous sulfate 200 mg three times daily for at least 3 months after anemia correction. 2

• Adding ascorbic acid (vitamin C) enhances iron absorption and may improve response in patients with partial resistance to oral iron 1, 2
• Investigate the source of iron loss before treating—in adult men and post-menopausal women, gastrointestinal blood loss is the most common cause and malignancy must be excluded 1, 2, 3
• Intravenous iron (iron sucrose or iron gluconate) should be used for patients who fail oral therapy due to malabsorption, intolerance, or ongoing blood loss 1, 2

Common pitfall: Failing to investigate the underlying cause of iron deficiency can miss gastrointestinal malignancy, which may present asymptomatically with iron deficiency anemia. 1

Iron Refractory Iron Deficiency Anemia (IRIDA)

IRIDA due to TMPRSS6 gene defects presents with microcytic anemia, remarkably low transferrin saturation, and resistance to oral iron. 1

• Most patients with severe TMPRSS6 defects do not respond to oral iron and require intravenous iron administration 1
• Repeated intravenous iron (iron sucrose or iron gluconate) increases hemoglobin and ferritin, though complete normalization is rarely achieved 1
• Diagnosis requires homozygous or compound heterozygous pathogenic TMPRSS6 mutations to confirm with certainty 1

Genetic Disorders of Iron Metabolism or Heme Synthesis

When ferritin and/or transferrin saturation are elevated, or when low transferrin saturation occurs with low-normal ferritin (>20 mg/L), consider genetic disorders. 1

• Family history, refractoriness to iron supplementation, neurologic disease, or photosensitivity suggest these rare genetic conditions 1
• In sideroblastic anemias, iron overload is of greater consequence than the anemia itself—unrecognized tissue iron loading can lead to severe morbidity and mortality 1
• Allogeneic hematopoietic stem cell transplantation is the only curative treatment for severe genetic disorders like congenital erythropoietic porphyria 1
• Chronic erythrocyte transfusion with iron chelation is recommended for symptomatic management when transplant is not feasible 1

Thalassemia Trait

Do NOT initiate empiric iron therapy before confirming iron deficiency, as this causes iron overload in thalassemia patients. 4

• Thalassemia trait typically shows microcytosis disproportionate to anemia (MCV 60-70 fL), elevated RBC count (>5.0 million/μL), and normal or elevated ferritin 4, 3
• Hemoglobin electrophoresis showing elevated HbA2 confirms beta-thalassemia trait 3, 5
• Genetic counseling and partner testing are essential, particularly for reproductive planning 4

Anemia of Chronic Disease

Characterized by low iron, low total iron-binding capacity (TIBC), and normal or high ferritin—treatment focuses on managing the underlying chronic condition. 2, 3

Monitoring and Follow-Up

Monitor hemoglobin and red cell indices at 3-month intervals for one year, then annually after initiating iron therapy. 2

• An acceptable response is hemoglobin increase of at least 2 g/dL within 4 weeks of treatment 2
• In genetic disorders requiring iron supplementation or transfusions, monitor iron status closely to detect toxic iron loading early 2

Critical Pitfalls to Avoid

Treating all microcytosis as iron deficiency without confirming the diagnosis can cause iron overload in thalassemia patients and delay diagnosis of genetic disorders. 1, 4

Failing to investigate gastrointestinal blood loss in men and post-menopausal women can miss occult malignancy. 1, 2

Not considering genetic testing in patients with refractory microcytic anemia despite adequate iron supplementation delays appropriate diagnosis and management. 2