What does a low mean corpuscular hemoglobin (MCH) and/or low mean corpuscular hemoglobin concentration (MCHC) on a complete blood count (CBC) indicate?

What Low MCH and MCHC Mean on a Complete Blood Count

Low MCH (mean corpuscular hemoglobin) and low MCHC (mean corpuscular hemoglobin concentration) indicate hypochromic red blood cells—cells that contain less hemoglobin than normal—and iron deficiency is by far the most common cause. 1

Primary Interpretation

MCH is actually a more reliable marker of iron deficiency than MCV or MCHC because it is less dependent on storage conditions and laboratory equipment, and it decreases in both absolute and functional iron deficiency. 2, 1 When you see low MCH with low MCHC, you are looking at red blood cells that are underfilled with hemoglobin, which strongly suggests insufficient iron availability for hemoglobin synthesis. 3

Stages of Iron Deficiency Reflected in Lab Values

Iron deficiency progresses through predictable stages that are reflected in CBC parameters 4:

• Early stage: Anisocytosis (elevated RDW) and increased percentage of microcytic cells appear first, while hemoglobin may still be normal and transferrin saturation drops below 32%. 4
• Middle stage: MCV and MCH decline, hemoglobin becomes mildly low (but usually above 9 g/dL), and transferrin saturation falls below 16%. 4
• Advanced stage: MCHC finally drops, hemoglobin falls below 9 g/dL, and transferrin saturation remains below 16%. 4

This means that by the time MCHC is low, you are looking at fairly advanced iron deficiency. 4

Immediate Diagnostic Workup Required

Order a complete iron panel immediately: serum ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), and C-reactive protein (CRP). 5, 1 The CRP is essential because ferritin is an acute-phase reactant and can be falsely normal or elevated during inflammation, infection, malignancy, or liver disease despite true iron deficiency. 3

Interpreting Ferritin Results

Serum ferritin is the single most specific test for iron deficiency 2, 1:

• Ferritin <15 μg/L: Confirms absent iron stores—iron deficiency is certain. 2, 1
• Ferritin <30 μg/L: Indicates low body iron stores in patients without inflammation. 2, 1
• Ferritin 30-100 μg/L with inflammation: May still indicate iron deficiency; suspect combined iron deficiency and anemia of chronic disease. 3
• Ferritin >150 μg/L: Makes absolute iron deficiency unlikely even with concurrent inflammation. 2, 3

Transferrin saturation <16-20% supports iron deficiency and is less affected by inflammation than ferritin. 1, 3

Additional Essential Tests

• Reticulocyte count: A low or inappropriately normal reticulocyte count in anemia indicates inadequate bone marrow response to red cell loss. 5
• Complete blood count with MCV: Determines whether the anemia is microcytic (MCV <80 fL), which further supports iron deficiency. 5

Differential Diagnosis When Iron Studies Are Normal

If iron studies come back normal despite low MCH and MCHC, order hemoglobin electrophoresis—especially in patients of Mediterranean, African, or Southeast Asian descent—to evaluate for thalassemia trait. 1, 3 In thalassemia trait, the MCV is typically reduced out of proportion to the degree of anemia, and patients have microcytosis with low MCH but normal iron parameters. 2, 1

Other conditions to consider when iron studies are normal include 3:

• Anemia of chronic disease: Usually presents with normocytic anemia, low serum iron, ferritin >100 μg/L, and TSAT <20%. 3
• Sideroblastic anemia: Can present with microcytosis and hypochromia. 3
• Combined deficiencies: In patients with simultaneous iron and vitamin B12/folate deficiency, the MCV may appear normal while MCH and MCHC remain low. 3

Critical Pitfalls to Avoid

Do not rely on MCV alone, as iron deficiency can present with normal MCV in early stages, and MCH may be more sensitive. 2, 3 The combination of low MCH with elevated RDW is highly suggestive of iron deficiency even when MCV remains normal. 5

Do not dismiss apparently normal ferritin values in inflammatory states. Use higher ferritin thresholds (45-100 μg/L) to diagnose iron deficiency when inflammation is present. 2, 1 Ferritin is an acute-phase reactant and can mask true iron deficiency during infection, inflammatory bowel disease, malignancy, or chronic inflammatory conditions. 3

Do not forget to investigate the underlying cause of iron deficiency, as it often indicates ongoing blood loss requiring evaluation. 1 In adult men and postmenopausal women with confirmed iron deficiency, gastrointestinal evaluation is mandatory because GI blood loss is the most common cause. 3

Treatment Approach for Confirmed Iron Deficiency

Initiate oral iron supplementation with ferrous sulfate 325 mg (65 mg elemental iron) once to three times daily between meals. 1 Expect hemoglobin to increase approximately 1-2 g/dL every 2-4 weeks. 1

A rise in hemoglobin of ≥10 g/L (≈1 g/dL) within 2 weeks of iron therapy strongly confirms absolute iron deficiency, even if iron study results were equivocal. 2, 1 This therapeutic response serves as both diagnostic confirmation and treatment. 3

Continue iron supplementation for 3-6 months after hemoglobin normalizes to replenish iron stores, and recheck hemoglobin, reticulocytes, and iron studies after 4-8 weeks of therapy. 1 Consider parenteral iron if the patient is intolerant to oral iron, has poor response to oral therapy, or has severe anemia requiring rapid correction. 1