What are mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) and their clinical significance?

Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC)

Definitions and Measurement

MCH represents the average mass of hemoglobin per red blood cell (measured in picograms), while MCHC measures the concentration of hemoglobin in a given volume of packed red blood cells (measured in g/dL). 1

• MCH is calculated from hemoglobin and red blood cell count, while MCHC is derived from hemoglobin and hematocrit. 2
• MCHC values significantly above the reference range (typically 32-36 g/dL) are not physiologically possible due to limitations on hemoglobin solubility. 3
• These parameters are routinely reported as part of a standard complete blood count by automated analyzers. 1

Clinical Significance in Anemia Evaluation

Low MCH and MCHC indicate hypochromic anemia, most commonly caused by iron deficiency, followed by thalassemia and chronic inflammatory conditions. 1, 4

Iron Deficiency

• MCH is a more reliable marker than MCV for detecting iron deficiency because it decreases in both absolute and functional iron deficiency and is less dependent on storage conditions and counting equipment. 4
• In iron deficiency, MCH decreases along with MCV, while red cell distribution width (RDW) increases. 4
• MCH may be more sensitive for iron deficiency than MCV alone. 4
• In a diagnostic accuracy study, MCH showed an area under the ROC curve of 0.67 for diagnosing iron deficiency in adolescents. 5

Thalassemia

• Thalassemia (particularly alpha and beta thalassemia trait) causes microcytosis and hypochromia with low MCH and MCHC. 4
• In thalassemia, MCV is typically reduced out of proportion to the level of anemia, helping distinguish it from iron deficiency. 4
• Low MCV with RDW ≤14.0% suggests thalassemia minor, while low MCV with RDW >14.0% suggests iron deficiency. 4

Chronic Disease

• Chronic inflammatory conditions can cause reduced MCH and MCHC, though this is less common than in iron deficiency. 4
• Mean corpuscular volume (MCV) is considered a late marker of iron deficiency in the context of anemia evaluation. 1

Diagnostic Approach When MCH/MCHC Are Low

Begin by measuring serum ferritin and transferrin saturation to distinguish iron deficiency from other causes of hypochromic anemia. 1, 4

Iron Studies Interpretation

• Serum ferritin <15 μg/L indicates absent iron stores; <30 μg/L indicates low body iron stores. 4
• Transferrin saturation <16-20% indicates insufficient circulating iron for erythropoiesis. 4
• Ferritin is an acute phase reactant and can be falsely normal or elevated during inflammation, infection, malignancy, or liver disease despite true iron deficiency. 4
• In the presence of inflammation, ferritin up to 100 μg/L may still indicate iron deficiency, but ferritin >150 μg/L essentially excludes absolute iron deficiency even with concurrent inflammation. 4

Algorithmic Approach

• If ferritin <30 μg/L (or <100 μg/L with inflammation) AND transferrin saturation <20%, diagnose iron deficiency anemia and initiate oral iron supplementation. 4
• When ferritin >100 μg/L AND transferrin saturation <20%, diagnose anemia of chronic disease and focus treatment on the underlying inflammatory condition. 4
• For ferritin 30-100 μg/L, suspect combined iron deficiency and anemia of chronic disease; consider a therapeutic trial of iron while concurrently managing the inflammatory disease. 4
• Normal iron studies with microcytosis and hypochromia warrant hemoglobin electrophoresis, particularly in patients with appropriate ethnic background for thalassemia. 4

Critical Pitfalls to Avoid

• In patients with combined deficiencies (iron plus B12/folate), MCV may appear normal while MCH and MCHC remain low. 4
• In adult men and post-menopausal women with iron deficiency, gastrointestinal evaluation is mandatory as GI blood loss is the most common cause. 4
• Abnormalities in two or more cell lines (white blood cells, hemoglobin, and platelets) should be evaluated carefully and likely warrant discussion with a hematologist. 1
• Elevated MCHC values should prompt critical evaluation of the peripheral smear, as they can indicate certain types of hemolytic anemia and are not physiologically possible above certain thresholds. 3

Special Considerations

• In hemochromatosis, MCH and MCHC values are typically elevated due to increased iron uptake and hemoglobin synthesis by immature erythroid cells. 6, 7
• Therapeutic response to 3 weeks of oral iron supplementation confirms iron deficiency diagnosis when other tests are equivocal. 4