What is the diagnosis and treatment for low Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC)?

Diagnosis of Low MCH and MCHC

Low MCH and MCHC indicate hypochromic anemia, most commonly caused by iron deficiency, and require immediate iron studies (serum ferritin and transferrin saturation) to confirm the diagnosis and guide treatment. 1, 2

Understanding the Laboratory Findings

Low MCH (Mean Corpuscular Hemoglobin) is a more reliable marker of iron deficiency than MCHC because it is less dependent on storage conditions and laboratory equipment, and decreases in both absolute and functional iron deficiency. 1, 2

• Low MCHC (Mean Corpuscular Hemoglobin Concentration) indicates hypochromia, meaning red blood cells contain less hemoglobin than normal 1, 3
• These findings together strongly suggest iron deficiency anemia, though other causes must be excluded 3, 4

Immediate Diagnostic Workup

Obtain the following tests to establish the diagnosis:

• Serum ferritin - the single most specific test for iron deficiency, with levels <15 μg/L confirming absent iron stores and <30 μg/L indicating low body iron stores 1, 2
• Transferrin saturation - values <16-20% support iron deficiency and are less affected by inflammation than ferritin 1, 2
• Complete blood count with MCV - to determine if the anemia is microcytic (MCV <80 fL), which further supports iron deficiency 1, 3
• Reticulocyte count - to assess bone marrow response; low or normal values indicate impaired red cell production 1, 2
• C-reactive protein (CRP) - to assess for inflammation, which can falsely elevate ferritin 2, 3

Interpreting Ferritin in Context

Critical caveat: Ferritin is an acute phase reactant and can be falsely normal or elevated in the presence of inflammation, chronic disease, malignancy, or liver disease. 1

• In patients without inflammation: ferritin <30 μg/L confirms iron deficiency 1
• In patients with inflammation (elevated CRP or active disease): ferritin up to 100 μg/L may still indicate iron deficiency 1, 2
• Ferritin >150 μg/L makes absolute iron deficiency unlikely even with inflammation 1
• If ferritin is 30-100 μg/L with inflammation, consider a combination of true iron deficiency and anemia of chronic disease 1

Differential Diagnosis Algorithm

If iron studies confirm iron deficiency (low ferritin and/or low transferrin saturation):

• Investigate the underlying cause - gastrointestinal bleeding in adult men and postmenopausal women, menstrual losses in premenopausal women, or malabsorption 1, 2, 3
• Begin oral iron supplementation as first-line therapy 3

If iron studies are normal despite low MCH/MCHC:

• Consider thalassemia trait - obtain hemoglobin electrophoresis, particularly in patients of Mediterranean, African, Middle Eastern, or Southeast Asian descent 1, 2
• In thalassemia, MCV is typically reduced out of proportion to the degree of anemia 1
• Consider anemia of chronic disease - assess for underlying inflammatory conditions with ferritin >100 μg/L and transferrin saturation <20% 1
• Consider sideroblastic anemia - rare cause requiring bone marrow examination 1

Treatment Approach for Confirmed Iron Deficiency

Initiate oral iron supplementation:

• Ferrous sulfate 325 mg (65 mg elemental iron) 1-3 times daily between meals 3
• Expect hemoglobin increase of approximately 1-2 g/dL every 2-4 weeks 3
• Continue iron supplementation for 3-6 months after hemoglobin normalizes to replenish iron stores 3
• Check hemoglobin, reticulocytes, and iron studies after 4-8 weeks of therapy 3

Consider parenteral iron if:

• Patient is intolerant to oral iron 3
• Poor response to oral iron after 4-8 weeks 3
• Severe anemia requiring rapid correction 3
• Malabsorption is suspected 5

Common Pitfalls to Avoid

• Do not rely on MCV alone - iron deficiency can present with normal MCV in early stages, and MCH may be more sensitive 1, 6
• Do not dismiss normal ferritin in inflammatory states - use the higher cutoff of 45-100 μg/L depending on inflammation severity 1
• Do not stop investigating if one test is normal - isolated abnormalities of MCV or ferritin may not be diagnostic; look for patterns across multiple parameters 7
• Do not forget to investigate the cause - iron deficiency in adults often indicates ongoing blood loss requiring evaluation 1, 3