Causes of Low MCH and MCHC
Low MCH (Mean Corpuscular Hemoglobin) and MCHC (Mean Corpuscular Hemoglobin Concentration) are primarily caused by iron deficiency, which impairs hemoglobin synthesis in developing red blood cells, resulting in hypochromic (pale) red cells. 1
Primary Causes
Iron Deficiency
- Iron deficiency is the most common cause of reduced MCH and MCHC, occurring when insufficient iron is available for hemoglobin synthesis in erythroid precursors 1
- MCH is a more reliable marker than MCV for detecting iron deficiency because it is less dependent on storage conditions and counting equipment, and decreases in both absolute and functional iron deficiency 1
- Iron deficiency progresses in stages: anisocytosis and microcytosis appear first, followed by decreased MCV and MCH, with MCHC declining only in the final, most severe stage when hemoglobin typically falls below 9 g/dL 2
- In children with low iron availability for erythropoiesis, MCH decreases along with MCV, while RDW increases 1
Thalassemia and Hemoglobinopathies
- Thalassemia (particularly alpha and beta thalassemia trait) causes microcytosis and hypochromia with low MCH and MCHC 1, 3
- In thalassemia, MCV is typically reduced out of proportion to the level of anemia, helping distinguish it from iron deficiency 1
- When alpha-thalassemia coexists with iron deficiency, Hb, MCV, MCHC, and MCH values are significantly lower compared to isolated alpha-thalassemia 3
Anemia of Chronic Disease
- Chronic inflammatory conditions can cause reduced MCH and MCHC, though this is less common than in iron deficiency 1
- Both microcytosis and hypochromia lose sensitivity for iron deficiency in the presence of chronic disease 1
Sideroblastic Anemia
- This rare disorder of heme synthesis can present with microcytosis and hypochromia, resulting in low MCH and MCHC 1
Diagnostic Approach
Initial Laboratory Evaluation
- Serum ferritin is the single most useful marker for iron deficiency, with levels <15 μg/L indicating absent iron stores and <30 μg/L indicating low body iron stores 1
- Transferrin saturation provides insight into circulating iron available for erythropoiesis 1
- Combined assessment of ferritin and transferrin saturation is useful for diagnosing absolute versus functional iron deficiency 1
Key Diagnostic Distinctions
- In iron deficiency, MCHC is significantly lower than in other causes of microcytic anemia 4, 3
- The difference between calculated MCHC and directly measured MCHC shows potential value for differentiating iron deficiency from other causes of microcytic anemia 4
- Low MCV with RDW >14.0% suggests iron deficiency, while low MCV with RDW ≤14.0% suggests thalassemia minor 5
Important Caveats
- Serum ferritin is an acute phase protein and can be falsely normal or elevated in inflammatory conditions despite true iron deficiency; ferritin >150 μg/L is unlikely to occur with absolute iron deficiency even with inflammation 1
- MCH may be more sensitive for iron deficiency than MCV 1
- In patients with combined deficiencies (iron plus B12/folate), MCV may appear normal while MCH and MCHC remain low 5, 6
When to Suspect Alternative Diagnoses
- Normal iron studies with microcytosis and hypochromia warrant hemoglobin electrophoresis, particularly in patients with appropriate ethnic background for thalassemia 1
- In adult men and post-menopausal women with iron deficiency, gastrointestinal evaluation is mandatory as GI blood loss is the most common cause 5
Clinical Significance
MCH decreases earlier in iron deficiency than MCHC, making it a more sensitive early marker 2. MCHC typically remains normal until severe iron deficiency develops with hemoglobin below 9 g/dL and transferrin saturation below 16% 2. This temporal sequence means that low MCHC indicates advanced iron depletion requiring urgent evaluation and treatment.