What is the appropriate evaluation and management for an adult with a newly identified low mean corpuscular hemoglobin?

Evaluation and Management of Low Mean Corpuscular Hemoglobin (MCH)

Low MCH indicates hypochromic anemia and requires immediate iron studies to confirm iron deficiency, which is the most common cause, followed by investigation of the underlying source of iron loss. 1

Initial Laboratory Evaluation

Order iron studies immediately when low MCH is identified, as MCH is a more reliable marker of iron deficiency than MCV because it is less dependent on storage conditions and laboratory equipment, and decreases in both absolute and functional iron deficiency. 2, 1

Essential First-Line Tests

• Serum ferritin is the single most specific test for iron deficiency in the absence of inflammation 2, 1, 3:

  • <15 μg/L confirms absent iron stores 2, 1
  • <30 μg/L indicates low body iron stores 2, 1
  • 30-100 μg/L with inflammation suggests combined iron deficiency and anemia of chronic disease 3

  • 150 μg/L essentially excludes absolute iron deficiency even with concurrent inflammation 3, 4

• Transferrin saturation provides insight into circulating iron available for red cell production 1, 3:

  • <16-20% indicates insufficient iron for erythropoiesis 1, 3
  • Less affected by inflammation than ferritin 1

• Complete blood count with MCV determines if anemia is microcytic, which further supports iron deficiency 1

• C-reactive protein (CRP) assesses for inflammation that can falsely elevate ferritin 1

Critical Pitfall to Avoid

Do not dismiss apparently normal ferritin levels in patients with inflammatory conditions (infection, malignancy, liver disease, chronic inflammatory diseases), as ferritin is an acute phase reactant and can be falsely normal or elevated despite true iron deficiency. 2, 3, 4 In inflammatory states, use higher ferritin cutoffs (45-100 μg/L) to diagnose iron deficiency. 2, 3

Diagnostic Algorithm Based on Iron Studies

If Iron Deficiency is Confirmed (Ferritin <30 μg/L or <100 μg/L with inflammation)

Investigate the underlying cause immediately, as iron deficiency in adults is presumed to be caused by blood loss until proven otherwise. 1, 5

Mandatory Evaluation in Adult Men and Post-Menopausal Women

• Upper endoscopy and colonoscopy to exclude gastrointestinal malignancy, as GI blood loss is the most common cause 1, 4
• Small bowel biopsy during endoscopy to rule out celiac disease, as 2-3% of patients with iron deficiency anemia have celiac disease 3
• Screen for NSAID use, which causes occult GI bleeding 4

Additional Considerations in Pre-Menopausal Women

• Assess menstrual blood loss patterns 4
• If menstrual losses do not explain severity, proceed with GI evaluation 4

If Iron Studies Are Normal Despite Low MCH

Order hemoglobin electrophoresis, particularly in patients with appropriate ethnic background (Mediterranean, African, Southeast Asian descent), as thalassemia trait causes microcytosis with low MCH but normal iron studies. 2, 1, 3 In thalassemia, MCV is typically reduced out of proportion to the level of anemia. 2, 3

Other diagnoses to consider include anemia of chronic disease and sideroblastic anemia. 2, 1, 5

Treatment Approach for Confirmed Iron Deficiency

First-Line Oral Iron Therapy

• Initiate ferrous sulfate 325 mg (65 mg elemental iron) 1-3 times daily between meals 1
• Expect hemoglobin increase of approximately 1-2 g/dL every 2-4 weeks 1
• Continue iron supplementation for 3-6 months after hemoglobin normalizes to replenish iron stores 1, 4
• Check hemoglobin, reticulocytes, and iron studies after 4-8 weeks of therapy 1

When to Use Intravenous Iron

Consider parenteral iron if: 1, 4

• Patient is intolerant to oral iron
• Poor response to oral iron after 4-8 weeks
• Malabsorption is present
• Severe anemia requiring rapid correction
• Inflammatory bowel disease is present

Diagnostic Confirmation Through Treatment Response

A hemoglobin rise ≥10 g/L within a 2-week timeframe in anemic patients is highly suggestive of absolute iron deficiency, even if iron study results are equivocal. 2 Therapeutic response to 3 weeks of oral iron supplementation confirms iron deficiency diagnosis when other tests are equivocal. 3

Key Clinical Pitfalls

• Do not rely on MCV alone, as iron deficiency can present with normal MCV in early stages, and MCH may be more sensitive for detecting iron deficiency 1, 3
• Do not forget that low MCH with normal MCV may represent early iron deficiency before microcytosis develops 4
• Do not skip investigation of the underlying cause, as iron deficiency often indicates ongoing blood loss requiring evaluation, and the possibility of gastrointestinal malignancy must be considered 1, 4, 5