What is the best course of action and treatment plan for a patient with hypochromic microcytic anemia, including options for those who cannot tolerate the constipation caused by iron treatment?

Management of Hypochromic Microcytic Anemia

First-Line Treatment

Start oral iron supplementation with ferrous sulfate 324 mg (65 mg elemental iron) once to three times daily for at least three months after anemia correction to replenish iron stores. 1, 2

Oral Iron Therapy Details

• Dosing options: Ferrous sulfate 200-324 mg three times daily is the standard regimen 1, 2
• Enhance absorption: Add ascorbic acid (vitamin C) to improve iron uptake 1, 2
• Expected response: Hemoglobin should rise ≥10 g/L (≥1 g/dL) within 2 weeks, confirming iron deficiency 1, 2, 3
• Duration: Continue for at least 3 months after hemoglobin normalizes to replete iron stores 1, 2, 3

Common Side Effects

• Gastrointestinal discomfort, nausea, constipation, or diarrhea are expected with oral iron 4
• Avoid taking within 2 hours of tetracycline antibiotics due to absorption interference 4

Options for Patients Unable to Tolerate Constipation

Alternative Oral Formulations

If ferrous sulfate causes intolerable constipation, switch to alternative oral iron formulations such as ferrous gluconate or ferrous fumarate. 1, 2

• These alternative formulations may be better tolerated while maintaining efficacy 1, 2
• Iron bisglycinate formulations offer enhanced GI tolerability and improved absorption 5

Intravenous Iron Therapy

For patients with true oral intolerance or malabsorption, intravenous iron (iron sucrose or iron gluconate) is the appropriate next step. 2, 6

• Indications: Malabsorption, losses exceeding maximal oral replacement capacity, or genuine intolerance to all oral formulations 2, 6
• Expected response: Hemoglobin increase of at least 2 g/dL within 4 weeks 2
• Formulations: Iron sucrose or iron gluconate are preferred IV options 2

Diagnostic Workup Before Treatment

Essential Laboratory Tests

• Serum ferritin: Most specific test for iron deficiency; <15 μg/L indicates absent stores, <30 μg/L indicates low stores, and <45 μg/L provides optimal sensitivity/specificity 1, 2, 3
• Transferrin saturation (TSAT): More sensitive than hemoglobin alone for detecting iron deficiency 1, 2
• Complete blood count: Low MCV with elevated RDW (>14.0%) strongly suggests iron deficiency rather than thalassemia 1, 2, 3

Investigate Underlying Cause

In adults with confirmed iron deficiency, investigate the source of iron loss—particularly gastrointestinal bleeding or malignancy. 1, 2

• Men with Hb <110 g/L or non-menstruating women with Hb <100 g/L warrant fast-track GI referral 2
• Upper and lower endoscopy should be performed to exclude malignancy, especially in patients over 50 years 1
• Consider celiac disease screening if malabsorption is suspected 2

Monitoring Protocol

• Initial monitoring: Check hemoglobin, MCV, and iron studies at 2 weeks, 4 weeks, and 3 months 2, 3
• Long-term follow-up: Monitor at three-monthly intervals for one year, then after a further year 1, 2
• Provide additional oral iron if hemoglobin or MCV falls below normal during follow-up 1, 2, 3

When Oral Iron Fails

Evaluation for Non-Response

If no hemoglobin rise occurs within 2-4 weeks, consider non-compliance, ongoing blood loss, malabsorption, or rare genetic disorders. 2

• Malabsorption: Proceed to IV iron therapy 2, 6
• Ongoing blood loss: Intensify investigation for source 1, 2
• Genetic disorders: Consider testing for IRIDA, SLC11A2, STEAP3, SLC25A38, ALAS2, or ABCB7 defects if extreme microcytosis (MCV <70) or family history present 2

Special Genetic Considerations

• X-linked sideroblastic anemia (ALAS2 defects): Trial pyridoxine (vitamin B6) 50-200 mg daily initially, then maintain lifelong supplementation at 10-100 mg daily 1, 2, 7
• IRIDA (TMPRSS6 defects): Requires repeated IV iron (iron sucrose or iron gluconate), as oral iron is typically ineffective 2
• Vitamin B6 deficiency: Consider in post-gastrointestinal surgery patients with therapy-resistant microcytic anemia 7

Critical Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency: Differentiate from anemia of chronic disease, thalassemia, and sideroblastic anemia to avoid unnecessary iron therapy 2
• Check hemoglobin electrophoresis if microcytosis persists with normal iron studies or if MCV is disproportionately low relative to anemia degree 2
• Avoid overlooking combined deficiencies: Iron deficiency can coexist with B12 or folate deficiency 1, 2
• Monitor for iron overload in patients receiving multiple transfusions or long-term IV iron therapy 2