What is the approach to a patient with mildly low Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC) levels?

Approach to Mildly Low MCH and MCHC

Mildly low MCH and MCHC indicate hypochromic anemia requiring immediate iron studies (serum ferritin and transferrin saturation) to confirm iron deficiency, which is the most common cause and must be diagnosed and treated promptly. 1

Initial Diagnostic Workup

Order the following tests immediately:

• Serum ferritin - the single most specific test for iron deficiency 2, 1
• Transferrin saturation - provides additional confirmation and is less affected by inflammation 1
• Complete blood count with MCV - to assess for microcytosis and classify the anemia 1
• C-reactive protein (CRP) - to identify inflammation that may falsely elevate ferritin 1
• Reticulocyte count - to assess bone marrow response 1

Interpreting Iron Studies

Without Inflammation (Normal CRP):

• Ferritin <15 μg/L = absent iron stores, confirms iron deficiency 2, 1
• Ferritin <30 μg/L = low iron stores, indicates iron deficiency 2, 1
• Ferritin <45 μg/L = optimal cutoff balancing sensitivity and specificity 2

With Inflammation (Elevated CRP):

• Ferritin up to 100 μg/L may still indicate iron deficiency 1, 3
• Ferritin 30-100 μg/L suggests combined iron deficiency and anemia of chronic disease 3, 4
• Ferritin >150 μg/L essentially excludes absolute iron deficiency even with inflammation 2, 3, 4

Critical pitfall: Ferritin is an acute phase protein and can be falsely normal or elevated during inflammation, infection, malignancy, or liver disease despite true iron deficiency 4. Use the higher cutoff of 45-100 μg/L depending on inflammation severity 1, 4.

Why MCH and MCHC Matter

• MCH is more reliable than MCV for detecting iron deficiency because it is less dependent on storage conditions and laboratory equipment, and decreases in both absolute and functional iron deficiency 2, 1, 4
• Low MCHC indicates hypochromia (red blood cells contain less hemoglobin than normal), which strongly suggests iron deficiency 1
• MCH may be more sensitive for iron deficiency than MCV and can detect early iron deficiency before microcytosis develops 2, 3

Differential Diagnosis Algorithm

If Iron Studies Confirm Iron Deficiency (Ferritin <30-45 μg/L or Transferrin Saturation <16-20%):

Investigate the underlying cause immediately: 1, 3

• Adult men and post-menopausal women: Gastrointestinal evaluation is mandatory - perform upper endoscopy and colonoscopy to exclude GI malignancy and blood loss 3, 4
• During upper endoscopy: Obtain small bowel biopsies as 2-3% of patients with iron deficiency have celiac disease 4
• Pre-menopausal women: Assess menstrual blood loss 3
• All patients: Screen for NSAID use (causes occult GI bleeding), evaluate for malabsorption if GI symptoms present, and consider chronic kidney disease 3

If Iron Studies Are Normal Despite Low MCH/MCHC:

Order hemoglobin electrophoresis to evaluate for thalassemia trait, particularly in patients of Mediterranean, African, Middle Eastern, or Southeast Asian descent 2, 3. In thalassemia, MCV is typically reduced out of proportion to the level of anemia 2, 4.

Consider other causes: 3

• Anemia of chronic disease (especially with inflammatory conditions)
• Sideroblastic anemia
• Combined deficiencies (iron plus B12/folate deficiency can mask microcytosis while MCH/MCHC remain low)

Treatment Approach for Confirmed Iron Deficiency

Start oral iron supplementation immediately: 1

• Ferrous sulfate 325 mg (65 mg elemental iron) 1-3 times daily between meals 1
• Expected response: Hemoglobin increase of 1-2 g/dL every 2-4 weeks 1
• Duration: Continue for 3-6 months after hemoglobin normalizes to replenish iron stores 1, 3

A good response to iron therapy (Hb rise ≥10 g/L within 2 weeks) is highly suggestive of absolute iron deficiency, even if iron study results are equivocal 2. This therapeutic trial confirms the diagnosis when other tests are unclear 4.

Consider intravenous iron if: 1, 3

• Patient is intolerant to oral iron
• Poor response to oral iron
• Malabsorption present
• Inflammatory bowel disease
• Severe anemia requiring rapid correction

Monitoring and Follow-up

• Repeat CBC after 4-8 weeks of treatment to assess response 3
• Monitor serum ferritin to ensure adequate repletion of iron stores 3
• If persistent or recurrent iron deficiency: Reassess compliance, consider repeat endoscopic evaluation, and evaluate for occult sources of blood loss 3

Key Clinical Pearls

• Do not rely on MCV alone - iron deficiency can present with normal MCV in early stages, and MCH may be more sensitive 1, 4
• Low MCH with normal MCV may represent early iron deficiency before microcytosis develops 3
• Both microcytosis and hypochromia lose sensitivity for iron deficiency in the presence of chronic disease, thalassemia, or vitamin B12/folate deficiency 2
• Always investigate the cause of iron deficiency, as it often indicates ongoing blood loss requiring evaluation 1, 3