What is the diagnosis and treatment for a patient with hypochromic anemia, indicated by low Mean Corpuscular Hemoglobin (MCH) and low Mean Corpuscular Hemoglobin Concentration (MCHC), but normal other blood parameters?

Low MCH and Low MCHC with Normal Other Parameters

The most likely diagnosis is iron deficiency anemia, and you should start oral ferrous sulfate 200 mg three times daily for at least 2-4 weeks, expecting a hemoglobin rise of ≥10 g/L within 2 weeks to confirm the diagnosis. 1, 2

Diagnostic Approach

MCH is actually more reliable than MCV as a marker of iron deficiency because it's less dependent on storage conditions and laboratory equipment, and it's reduced in both absolute and functional iron deficiency. 1, 2 Low MCH combined with low MCHC strongly suggests hypochromic anemia, most commonly from iron deficiency. 3, 1

Essential Initial Testing

• Serum ferritin is the single most useful test to confirm iron deficiency, with a cutoff of 45 μg/L providing optimal sensitivity and specificity in practice. 1, 2
• Ferritin <15 μg/L indicates absent iron stores, while <30 μg/L indicates low body iron stores. 1
• Add transferrin saturation (TSAT) if ferritin appears falsely normal due to inflammation (ferritin is an acute phase reactant). 3, 2
• TSAT <16-20% suggests iron deficiency, while TSAT <20% with ferritin >100 μg/L indicates anemia of chronic disease. 3, 1

Critical Pitfall to Avoid

Normal ferritin does not exclude iron deficiency in the presence of inflammation. In inflammatory conditions, ferritin up to 100 μg/L may still be consistent with iron deficiency. 1 This is why TSAT becomes essential when inflammation is suspected. 3, 2

Differential Diagnosis Beyond Iron Deficiency

While iron deficiency is most common, consider these alternatives if iron studies are normal or treatment fails:

• Thalassemia trait: Look for MCV disproportionately low relative to degree of anemia, normal or low RDW (≤14.0%), and appropriate ethnic background. 1, 2 Order hemoglobin electrophoresis if suspected. 1
• Anemia of chronic disease: TSAT <20% with ferritin >100 μg/L, presence of inflammatory markers. 3, 1
• Sideroblastic anemia: Consider if there's failure to respond to iron therapy. 2, 4

Treatment Algorithm

First-Line Therapy

• Start oral ferrous sulfate 200 mg three times daily for at least 2-4 weeks initially. 1, 2, 5
• Alternative formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate is not tolerated. 1
• Adding ascorbic acid (vitamin C) enhances iron absorption. 1
• Take with meals to minimize gastrointestinal discomfort such as nausea, constipation, or diarrhea. 5

Confirming the Diagnosis Through Treatment Response

A hemoglobin rise of ≥10 g/L within 2 weeks strongly confirms iron deficiency, even if initial iron studies were equivocal. 1, 2 This therapeutic trial is diagnostically valuable when iron studies are borderline or confounded by inflammation. 2

• If response is positive, continue iron therapy for 3 months total to replenish iron stores, not just correct anemia. 1, 2
• Check hemoglobin, MCV, and MCH after 2-4 weeks of therapy. 2

When to Escalate to IV Iron

Consider intravenous iron if:

• Malabsorption is present (celiac disease, H. pylori infection, autoimmune atrophic gastritis). 1
• Failure to respond to oral iron within 2-4 weeks despite adequate dosing and compliance. 1, 2
• Expect hemoglobin increase of at least 2 g/dL within 4 weeks of IV iron. 1

Investigation of Underlying Cause

You must investigate the source of iron loss in adults, particularly:

• Men with hemoglobin <110 g/L warrant fast-track GI referral. 1
• Non-menstruating women with hemoglobin <100 g/L warrant fast-track GI referral. 1
• Consider investigation at any level of anemia with confirmed iron deficiency, especially with more severe degrees. 1

Look for:

• Gastrointestinal blood loss: History of melena, hematochezia, or occult bleeding. 1
• Menstrual blood loss: Most common cause in premenopausal women. 1
• Malabsorption disorders: Screen for celiac disease if suspected. 1
• Dietary inadequacy: Though less common in developed countries. 1

Monitoring and Follow-Up

• Monitor hemoglobin and red cell indices at 3-monthly intervals for one year, then after a further year. 1
• Provide additional oral iron if hemoglobin or MCV falls below normal. 1
• Monitor for iron overload in patients receiving multiple transfusions or long-term therapy. 1

Rare Genetic Considerations (If Treatment Fails)

If there's failure to respond to both oral and IV iron, consider genetic disorders of iron metabolism:

• IRIDA (iron-refractory iron deficiency anemia): Remarkably low TSAT with low-to-normal ferritin, requires repeated IV iron. 1
• SLC11A2, STEAP3, SLC25A38, ALAS2 defects: Consider if extreme microcytosis (MCV <70) or family history present. 1
• X-linked sideroblastic anemia (ALAS2 defects): Trial of pyridoxine (vitamin B6) 50-200 mg daily. 1