What is the treatment for microcytic hypochromic anemia?

Treatment of Microcytic Hypochromic Anemia

Oral ferrous sulfate 200 mg (65 mg elemental iron) three times daily for at least 3 months after anemia correction is the first-line treatment for confirmed iron deficiency anemia, but you must first confirm iron deficiency with serum ferritin and RDW before starting iron therapy to avoid harm in thalassemia and genetic disorders. 1, 2

Diagnostic Confirmation Before Treatment

Do not treat empirically—confirm the diagnosis first:

• Measure serum ferritin, transferrin saturation, complete blood count with RDW, and examine the peripheral smear before initiating any iron therapy 1, 3
• Ferritin <15 μg/L confirms absent iron stores with 99% specificity; <30 μg/L indicates low body iron stores 1, 2
• Use a ferritin cutoff of 45 μg/L for optimal sensitivity and specificity, especially when inflammation may be present 1, 2, 3
• RDW >14.0% with low MCV strongly suggests iron deficiency anemia, while RDW ≤14.0% points toward thalassemia trait 1, 2, 3
• Transferrin saturation <16-20% confirms iron deficiency when ferritin may be falsely elevated by inflammation 2

Treatment Algorithm by Etiology

For Confirmed Iron Deficiency Anemia

Standard oral iron therapy:

• Ferrous sulfate 200 mg (65 mg elemental iron) three times daily is the recommended regimen 1, 2
• Continue treatment for at least 3 months after anemia correction to fully replenish iron stores 1, 2
• Alternative formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate is not tolerated 2
• Adding ascorbic acid (vitamin C) enhances iron absorption 2

Expected response and monitoring:

• Expect hemoglobin increase of at least 2 g/dL within 4 weeks of starting oral iron 1, 2
• A hemoglobin rise ≥10 g/L within 2 weeks confirms iron deficiency as the cause 2
• Monitor hemoglobin and red cell indices at 3-month intervals for one year, then annually 1, 2

When oral iron fails:

• Consider intravenous iron if malabsorption is present, oral iron is not tolerated, or rapid iron replenishment is necessary 2, 4
• Intravenous formulations include iron sucrose or iron gluconate 2
• Expect the same hemoglobin increase of at least 2 g/dL within 4 weeks with IV iron 2

For Thalassemia Trait

No iron supplementation unless concurrent iron deficiency is documented:

• Thalassemia trait requires no treatment in the absence of proven iron deficiency 1, 3
• Provide genetic counseling and family screening 1
• Iron supplementation in thalassemia without true deficiency can cause harm through iron overload 1, 3

For Genetic Disorders of Iron Metabolism

Iron-refractory iron deficiency anemia (IRIDA):

• Initial treatment is oral iron or oral iron combined with ascorbic acid 1
• If oral iron fails, intravenous iron (iron sucrose or iron gluconate) is required 2
• IRIDA is caused by TMPRSS6 mutations and typically shows remarkably low transferrin saturation with low-to-normal ferritin 2, 4

X-linked sideroblastic anemia (ALAS2 defects):

• Initial treatment with pyridoxine (vitamin B6) 50-200 mg per day 1, 2
• If responsive, continue lifelong supplementation at 10-100 mg daily 2

SLC25A38 defects:

• Hematopoietic stem cell transplantation (HSCT) is the only curative option 1, 2
• Symptomatic treatment includes erythrocyte transfusions and iron chelation therapy 2

SLC11A2 and STEAP3 defects:

• Treatment may include oral iron supplementation and/or erythropoietin (EPO) and/or erythrocyte transfusions based on individual needs 2
• For STEAP3 defects, manage systemic iron loading with chelation 2

For Iron Overload (in genetic disorders or transfusion-dependent patients)

• Phlebotomy is the preferred method when tolerated 1
• Iron chelation therapy is recommended when phlebotomies are not tolerated due to decreasing hemoglobin 1
• Monitor for iron overload with MRI of the liver in specific cases 2

Critical Pitfalls to Avoid

Never give iron empirically:

• Do not assume all microcytic anemia is iron deficiency—thalassemia and genetic disorders require different management 1, 3, 5
• Iron supplementation without confirming iron deficiency can cause harm in thalassemia and genetic iron metabolism disorders through iron overload 1, 3
• An extremely low MCV (such as 51 fL) raises strong suspicion for thalassemia trait or genetic disorders, not simple iron deficiency 3

Always investigate the source of iron loss:

• In adult men with hemoglobin <110 g/L or non-menstruating women with hemoglobin <100 g/L, fast-track gastrointestinal referral is warranted 2
• Common sources include gastrointestinal bleeding, heavy menstrual bleeding, malabsorption disorders (celiac disease, H. pylori, atrophic gastritis), and dietary inadequacy 2, 6, 4

Do not overlook combined deficiencies:

• Iron deficiency can coexist with vitamin B12 or folate deficiency, recognizable by elevated RDW 2
• Check B12 and folate levels if clinical suspicion exists 2

Special Considerations

In inflammatory conditions:

• Ferritin can be falsely elevated by inflammation, infection, malignancy, or liver disease 2, 7
• Use transferrin saturation <16-20% to confirm iron deficiency when ferritin is borderline (30-100 μg/L) 2
• Measure C-reactive protein to identify inflammatory states 2

Anemia of chronic disease:

• Characterized by ferritin >100 μg/L with transferrin saturation <20% 2, 7
• Treatment should primarily target the underlying disease 7
• Conventional therapy includes red blood cell transfusions, iron, and erythropoietin 7