What does a low Mean Corpuscular Hemoglobin (MCH) on a Complete Blood Count (CBC) indicate clinically?

Clinical Significance of Low MCH on CBC

A low Mean Corpuscular Hemoglobin (MCH) on a Complete Blood Count (CBC) most commonly indicates iron deficiency, which requires prompt evaluation for underlying causes, particularly gastrointestinal bleeding in adults. 1

What is MCH?

MCH measures the average amount of hemoglobin contained in each red blood cell. Normal values typically range from 27-33 picograms (pg) per cell. When MCH is low, it indicates hypochromia (reduced hemoglobin content in red blood cells).

Primary Causes of Low MCH

Low MCH is most commonly associated with:

1. Iron Deficiency - The most common cause, characterized by:

   • Reduced hemoglobin synthesis
   • Progressive development of microcytosis (small red cells)
   • Hypochromia (pale red cells) 1

2. Thalassemia - Hereditary disorders of hemoglobin synthesis:

   • Alpha or beta-thalassemia trait
   • Characterized by microcytosis with disproportionately normal hemoglobin 2

3. Anemia of Chronic Disease/Inflammation:

   • Functional iron deficiency despite adequate iron stores
   • Inflammatory cytokines impair iron utilization 1

4. Sideroblastic Anemia:

   • Defective heme synthesis
   • Iron accumulates in mitochondria of red cell precursors 3

5. Lead Toxicity:

   • Interferes with heme synthesis
   • More common in pediatric populations 3

Diagnostic Algorithm

1. First-line test: Serum ferritin measurement

   • Low ferritin (<30 μg/L) confirms iron deficiency 3
   • Note: Ferritin is an acute phase reactant and may be falsely elevated in inflammation 1

2. If ferritin is not low or is borderline:

   • Check transferrin saturation (TSAT) - <15% suggests iron deficiency 1
   • Total iron-binding capacity (TIBC)
   • Serum iron level
   • Consider inflammatory markers (CRP) 1

3. Additional tests to differentiate causes:

   • Red cell distribution width (RDW):
     • High RDW (>14%) with low MCH suggests iron deficiency
     • Normal RDW with low MCH suggests thalassemia trait 1
   • Hemoglobin electrophoresis:
     • Elevated HbA2 (>3.5%) suggests beta-thalassemia trait 2
     • Presence of Hb Bart's suggests alpha-thalassemia 4
   • Lead levels if exposure suspected 3

Clinical Significance and Management

1. For confirmed iron deficiency:

   • In adults: Must investigate for source of blood loss, particularly gastrointestinal tract 3
   • Consider endoscopy to rule out gastrointestinal malignancy
   • Iron replacement therapy

2. For thalassemia trait:

   • Genetic counseling
   • Avoid unnecessary iron therapy 2

3. For anemia of chronic disease:

   • Address underlying condition
   • Consider erythropoiesis-stimulating agents in selected cases 1

Important Clinical Pearls

• MCH may be a more reliable marker of iron deficiency than MCV as it is less dependent on storage and counting machine used 1
• MCH decreases earlier than MCHC in developing iron deficiency 5
• Three stages of progressive iron deficiency can be identified:
  1. Early: Anisocytosis and microcytosis with normal hemoglobin
  2. Intermediate: Declining MCV and MCH with mild anemia
  3. Advanced: Low MCHC with hemoglobin <9 g/dL 5
• Always consider thalassemia in patients with persistent microcytosis despite iron therapy, especially in at-risk ethnic populations 1
• Rare cases of microcytosis with elevated RBC count may occur in polycythemia with iron deficiency 6

Common Pitfalls to Avoid

• Assuming all microcytosis/low MCH is iron deficiency
• Failing to investigate for source of blood loss in adults with iron deficiency
• Overlooking thalassemia trait in patients from high-prevalence regions
• Misinterpreting normal ferritin in inflammatory states (may mask iron deficiency)
• Prescribing iron supplements for thalassemia trait patients who don't need them

By systematically evaluating low MCH with appropriate follow-up testing, clinicians can identify the underlying cause and implement appropriate management to improve patient outcomes.