Causes of Low MCH and MCHC
Iron deficiency is the predominant cause of low MCH and MCHC values, occurring when insufficient iron is available for hemoglobin synthesis in developing red blood cells. 1, 2
Primary Causes
Iron Deficiency (Most Common)
- Iron deficiency accounts for the majority of cases with reduced MCH and MCHC, manifesting as microcytic hypochromic anemia 1, 2
- MCH is actually more sensitive than MCV for detecting iron deficiency because it decreases in both absolute and functional iron deficiency and is less affected by storage conditions or equipment variability 1, 3
- In progressive iron deficiency, anisocytosis and microcytosis appear first, followed by declining MCV and MCH, with MCHC dropping only in the final stage when hemoglobin falls below 9 g/dL 4
- In adult men and postmenopausal women with iron deficiency, gastrointestinal blood loss is the most common etiology and mandates GI evaluation 5, 1, 2
Thalassemia
- Alpha and beta thalassemia trait cause microcytosis and hypochromia with low MCH and MCHC 1, 2
- Key distinguishing feature: MCV is reduced out of proportion to the degree of anemia in thalassemia compared to iron deficiency 1
- Low MCV with RDW ≤14.0% suggests thalassemia minor, while RDW >14.0% suggests iron deficiency 1, 2
Other Causes
- Sideroblastic anemia presents with microcytosis and hypochromia due to defective heme synthesis despite adequate iron availability 1, 2
- Chronic inflammatory conditions can reduce MCH and MCHC, though less commonly than iron deficiency 1
Diagnostic Approach
Initial Laboratory Evaluation
- Serum ferritin is the single most powerful test for iron deficiency: <15 μg/L indicates absent iron stores, <30 μg/L indicates low body iron stores 5, 1, 2
- 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 5, 1, 2
- Transferrin saturation <16-20% indicates insufficient circulating iron for erythropoiesis 5, 1, 2
- Combined ferritin and transferrin saturation assessment distinguishes absolute from functional iron deficiency 1, 2
Red Cell Indices Pattern Recognition
- Low MCV with elevated RDW (>14.0%) → iron deficiency 1, 2
- Low MCV with normal RDW (≤14.0%) → thalassemia minor 1, 2
- Normal MCV with low MCH/MCHC → consider combined deficiencies (iron plus B12/folate) 1
When Iron Studies Are Normal
- Normal iron studies with persistent microcytosis and hypochromia warrant hemoglobin electrophoresis, particularly in patients of Mediterranean, African, Middle Eastern, or Southeast Asian descent 1
Critical Pitfalls to Avoid
Ferritin Misinterpretation
- Ferritin is an acute phase reactant and can be falsely normal or elevated during inflammation, infection, malignancy, or liver disease despite true iron deficiency 5, 1, 2
- In inflammatory bowel disease specifically, ferritin 30-100 μg/L suggests combined iron deficiency and anemia of chronic disease 5
Diagnostic Accuracy Limitations
- MCH, MCV, and MCHC have only moderate diagnostic accuracy (area under ROC curve 0.60-0.73) for detecting empty iron stores, with normal values not excluding iron deficiency in anemic patients 3, 6
- At cutoff limits providing 90% sensitivity, specificity is only approximately 50% 3
Combined Deficiencies
- Concurrent B12 or folate deficiency can mask microcytosis, resulting in normal MCV while MCH and MCHC remain low 1
- Elevated RDW may be the only clue to combined deficiency states 5
Treatment Approach
Iron Deficiency Management
- In patients with confirmed iron deficiency anemia undergoing elective surgery, preoperative iron therapy (oral or intravenous) reduces transfusion requirements and increases hemoglobin within 2-4 weeks 5
- Therapeutic response to 3 weeks of oral iron supplementation confirms iron deficiency diagnosis when other tests are equivocal 5
- Small bowel biopsies should be obtained during upper endoscopy as 2-3% of patients with iron deficiency anemia have celiac disease 5