What is the initial workup for a patient with a low Mean Corpuscular Hemoglobin (MCH)?

Initial Workup for Low Mean Corpuscular Hemoglobin (MCH)

The initial workup for a patient with low Mean Corpuscular Hemoglobin (MCH) should include a complete blood count with differential, serum ferritin, iron studies (serum iron, total iron-binding capacity, transferrin saturation), and peripheral blood smear examination to differentiate between iron deficiency anemia and other microcytic anemias. 1, 2

Diagnostic Approach

Step 1: Complete Blood Count (CBC) with Differential

• Evaluate other red blood cell indices:
  • Mean Corpuscular Volume (MCV) - often low in iron deficiency
  • Mean Corpuscular Hemoglobin Concentration (MCHC)
  • Red Blood Cell (RBC) count
  • Hemoglobin and Hematocrit levels
  • Red Cell Distribution Width (RDW) - typically elevated in iron deficiency

Step 2: Iron Studies

• Serum ferritin (primary marker for tissue iron stores)
  • <15 μg/L is highly specific for iron deficiency (specificity 0.99)
  • <30 μg/L indicates absent/low iron stores in non-inflammatory states
  • <45 μg/L is considered optimal cutoff for clinical practice 1
• Transferrin saturation (<20% suggests iron deficiency)
• Serum iron level
• Total iron-binding capacity (TIBC)

Step 3: Peripheral Blood Smear Examination

• Evaluate RBC morphology for:
  • Microcytosis
  • Hypochromia
  • Anisocytosis (variation in cell size)
  • Poikilocytosis (variation in cell shape)

Differential Diagnosis Considerations

When evaluating low MCH, it's important to distinguish between:

1. Iron Deficiency Anemia:

   • Low ferritin, low serum iron, high TIBC, low transferrin saturation
   • Typically shows progressive decrease in MCH, MCV, and MCHC 2, 3

2. Thalassemia Trait:

   • Normal or elevated ferritin, normal iron studies
   • Consider hemoglobin electrophoresis (elevated HbA2 in beta-thalassemia trait) 3

3. Anemia of Chronic Disease:

   • Low serum iron, low TIBC, normal/high ferritin
   • Less severe reduction in MCH and MCV 3, 4

4. Lead Toxicity:

   • Consider in specific exposure risk populations
   • Blood lead level testing if suspected

5. Sideroblastic Anemia:

   • Rare cause of microcytosis with low MCH
   • May require bone marrow examination for diagnosis 3

Important Clinical Considerations

• MCH has been shown to have high diagnostic value for iron deficiency anemia with an area under the ROC curve of 0.81 in recent studies 2

• Relying solely on hemoglobin and hematocrit without iron studies may miss early iron depletion states, as these parameters decrease only when severe iron deficiency is present 5

• In adult patients with confirmed iron deficiency anemia, further investigation for source of blood loss is essential, particularly evaluation of the gastrointestinal tract to rule out malignancy 3

• Serum ferritin can be falsely elevated in inflammatory states, requiring higher cutoff values to diagnose iron deficiency in these conditions 1

• Reticulocyte count should be included to assess bone marrow response to anemia 1

• If initial testing is inconclusive, bone marrow examination with iron staining may be necessary in select cases 4

By following this systematic approach to low MCH, clinicians can efficiently diagnose the underlying cause and initiate appropriate treatment to address the specific etiology.