What is the management approach for a patient with microcytic hypochromic anemia, characterized by low hemoglobin (Hb), low hematocrit (Hct), low mean corpuscular volume (MCV), and low mean corpuscular hemoglobin (MCH)?

Management of Microcytic Hypochromic Anemia

Start with oral ferrous sulfate 200 mg three times daily for at least three months after hemoglobin normalizes, as iron deficiency anemia is the overwhelming cause of this presentation and responds predictably to treatment. 1, 2

Initial Diagnostic Workup

The minimum laboratory evaluation must include: 3, 1

• Serum ferritin (most specific test): <30 μg/L indicates low iron stores, <45 μg/L provides optimal sensitivity/specificity in practice 1, 2
• Transferrin saturation (TSAT): <16-20% confirms iron deficiency 1, 2
• Red cell distribution width (RDW): >14.0% with low MCV strongly suggests iron deficiency rather than thalassemia 1, 2
• C-reactive protein (CRP): If elevated, ferritin up to 100 μg/L may still indicate iron deficiency 3, 2
• Reticulocyte count: Low/normal indicates deficiency states; elevated suggests hemolysis 3

Critical distinction: Low MCV + RDW >14.0% = iron deficiency; Low MCV + RDW ≤14.0% = thalassemia minor. 1, 2

First-Line Treatment Protocol

Oral iron supplementation: 1, 2

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

Expected response: Hemoglobin should rise ≥10 g/L (≥1 g/dL) within 2 weeks, confirming iron deficiency. 1, 2

When Treatment Fails (No Response in 2-4 Weeks)

Investigate these causes systematically: 1, 2

1. Non-compliance or inadequate dosing (most common)

2. Ongoing blood loss:

   • Men with Hb <110 g/L or non-menstruating women with Hb <100 g/L warrant urgent GI evaluation 1
   • Heavy menstrual bleeding in premenopausal women 1

3. Malabsorption disorders: 3, 1

   • Celiac disease (screen with serology)
   • H. pylori infection
   • Autoimmune atrophic gastritis
   • Switch to IV iron (iron sucrose or iron gluconate) if malabsorption confirmed, expecting Hb rise ≥2 g/dL within 4 weeks 1, 2

4. Thalassemia trait: Order hemoglobin electrophoresis if MCV disproportionately low relative to anemia severity or if iron studies normal 1, 2

5. Anemia of chronic disease: TSAT <20% with ferritin >100 μg/L and elevated inflammatory markers 3, 1

Rare Genetic Causes (Consider if Refractory)

IRIDA (Iron-Refractory Iron Deficiency Anemia): 3, 1

• Remarkably low TSAT with low-to-normal ferritin
• Fails oral iron but may respond to IV iron (though rarely normalizes completely)
• Autosomal recessive TMPRSS6 mutations 3

X-linked sideroblastic anemia (ALAS2 defects): 3, 1

• Trial pyridoxine (vitamin B6) 50-200 mg daily initially
• If responsive, continue lifelong at 10-100 mg daily 3, 1

Other genetic disorders (SLC11A2, STEAP3, SLC25A38): Consider if extreme microcytosis (MCV <70), family history, or failure of all standard therapies. 3, 1

Monitoring Strategy

• First year: Check hemoglobin and MCV every 3 months 1, 2
• Second year: Recheck once 1, 2
• Provide additional oral iron if hemoglobin or MCV falls below normal 1, 2
• For transfusion-dependent patients: Monitor for iron overload; consider liver MRI to detect toxic iron loading early 1

Critical Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency: Anemia of chronic disease, thalassemia, and sideroblastic anemia require different management. 1
• Do not miss combined deficiencies: Iron deficiency can coexist with B12 or folate deficiency, especially in IBD patients or those with extensive small bowel disease. 3
• Do not overlook the source of iron loss: Always investigate GI or gynecologic blood loss in adults with confirmed iron deficiency. 1
• Do not use ferritin alone in inflammatory states: Add TSAT, as ferritin can be falsely elevated by inflammation. 3, 1, 2
• Mean corpuscular hemoglobin (MCH) is more reliable than MCV in iron deficiency because it's less dependent on storage conditions and is reduced in both absolute and functional iron deficiency. 1