What is the management approach for a patient with microcytic hypochromic anemia, characterized by decreased hemoglobin (Hb), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC)?

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 is the most common cause and should be treated empirically while investigating the underlying source of iron loss. 1, 2

Immediate Diagnostic Workup

Order serum ferritin first—it is the single most specific test for iron deficiency:

• Ferritin <15 μg/L confirms absent iron stores 1, 2
• Ferritin <30 μg/L indicates low body iron stores 1, 2
• Ferritin <45 μg/L provides optimal sensitivity/specificity cutoff in practice 1, 2
• Ferritin >150 μg/L makes iron deficiency unlikely 2

Add transferrin saturation (TSAT) to the initial workup:

• TSAT is more sensitive than hemoglobin alone for detecting iron deficiency 1, 2
• Low TSAT with low ferritin confirms iron deficiency anemia 1, 2

Use RDW to differentiate causes:

• Low MCV + RDW >14.0% strongly suggests iron deficiency anemia 1, 2, 3
• Low MCV + RDW ≤14.0% suggests thalassemia minor 1, 2, 3

First-Line Treatment Protocol

Prescribe oral ferrous sulfate 200 mg (65 mg elemental iron) three times daily:

• Continue for at least 3 months after anemia corrects to replenish iron stores 1, 2, 3
• Add ascorbic acid (vitamin C) to enhance absorption 1
• Alternative formulations if intolerant: ferrous gluconate or ferrous fumarate 1, 2

Expect hemoglobin rise ≥10 g/L within 2 weeks—this confirms iron deficiency: 1, 2, 3

• If no response by 2-4 weeks, suspect non-compliance, ongoing blood loss, malabsorption, or genetic disorders 2, 3
• Expected increase should be at least 2 g/dL within 4 weeks 2, 3

Investigate the Source of Iron Loss

In men and post-menopausal women, gastrointestinal blood loss is the most common cause: 1

• Fast-track GI referral for men with Hb <110 g/L or non-menstruating women with Hb <100 g/L 2
• Consider upper and lower endoscopy based on severity and risk factors 1

In premenopausal women, heavy menstrual bleeding is the leading cause: 2

• Evaluate menstrual history for excessive blood loss 2
• Screen for gastrointestinal sources if menstrual loss doesn't explain severity 1

Screen for malabsorption if dietary history suggests inadequate intake:

• Consider celiac disease testing 2
• Evaluate for inflammatory bowel disease 1

When Oral Iron Fails: Consider IV Iron or Genetic Disorders

Switch to intravenous iron if malabsorption is present:

• Use iron sucrose or iron gluconate 2, 3
• Expect hemoglobin increase of at least 2 g/dL within 4 weeks 2, 3

Suspect genetic disorders if:

• Ferritin is low-normal (>20 mg/L) with low TSAT 3
• Family history of refractory anemia 3
• Anemia incompletely responsive to iron supplementation 3
• Elevated ferritin with increased TSAT (consider SLC11A2 defects) 1

For Iron-Refractory Iron Deficiency Anemia (IRIDA):

• Oral iron is ineffective—do not waste time with it 2, 3
• Requires repeated intravenous iron (iron sucrose or iron gluconate) 2, 3
• Hemoglobin rarely normalizes completely 2

For X-linked Sideroblastic Anemia (ALAS2 defects):

• Start pyridoxine (vitamin B6) 50-200 mg daily 2, 3
• If responsive, continue lifelong maintenance at 10-100 mg daily 2, 3
• Avoid doses >200 mg daily to prevent neurotoxicity 2

Monitoring Schedule

Check hemoglobin and red cell indices at:

• 2 weeks (to confirm response) 3
• 4 weeks (to assess adequacy of response) 3
• 3 months (to ensure correction) 1, 2, 3
• Every 3 months for the first year 1, 2, 3
• Annually thereafter 3

Provide additional oral iron if hemoglobin or MCV falls below normal during follow-up: 1, 2

Monitor for iron overload in patients receiving:

• Multiple transfusions 2
• Long-term iron therapy for genetic disorders 2
• Consider liver MRI if serum ferritin doesn't exclude liver iron loading 1, 2

Critical Pitfalls to Avoid

Do not assume all microcytic anemia is iron deficiency:

• Anemia of chronic disease, thalassemia, and sideroblastic anemia must be differentiated 2, 3
• Unnecessary iron therapy can cause harm in genetic disorders 3

Do not overlook combined deficiencies:

• Iron deficiency can coexist with B12 or folate deficiency 1, 3
• Check B12 and folate if response to iron is suboptimal 1, 3

Order hemoglobin electrophoresis if:

• Microcytosis persists with normal iron studies 2
• Appropriate ethnic background (Mediterranean, African, Southeast Asian) 2
• MCV disproportionately low relative to degree of anemia 2

In genetic sideroblastic anemias, iron overload is more dangerous than the anemia itself:

• Unrecognized tissue iron loading causes severe morbidity and mortality 3
• Monitor ferritin and avoid exceeding 500 mg/L, especially in children 2

In cyanotic congenital heart disease, iron deficiency exacerbates hyperviscosity:

• Microcytic hypochromic iron-deficient red cells have decreased oxygen-carrying capacity and reduced deformability 4
• This further decreases tissue oxygenation and increases bleeding risk 4