What Decreased MCH and MCHC Indicate
Decreased MCH and MCHC indicate hypochromic anemia, most commonly caused by iron deficiency, and require immediate iron studies (serum ferritin, transferrin saturation, and CRP) to confirm the diagnosis and guide treatment. 1
Primary Interpretation
Low MCH 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
Low MCHC indicates hypochromia, meaning red blood cells contain less hemoglobin than normal, which strongly suggests iron deficiency anemia, though other causes must be excluded. 1
In the progression of iron deficiency, MCHC drops late in the disease course—typically when hemoglobin falls below 9 g/dL and transferrin saturation is less than 16%, representing the final stage of iron deficiency. 2
Immediate Diagnostic Workup
When you detect decreased MCH and MCHC, order the following tests immediately:
Serum ferritin (the single most specific test for iron deficiency): <15 μg/L confirms absent iron stores; <30 μg/L indicates low body iron stores. 1
Transferrin saturation: Values <16-20% support iron deficiency and are less affected by inflammation than ferritin. 1
C-reactive protein (CRP): Assesses for inflammation, which can falsely elevate ferritin and requires using higher ferritin thresholds (45-100 μg/L) for diagnosis. 1, 3
Complete blood count with MCV: Determines if the anemia is microcytic, which further supports iron deficiency. 1
Reticulocyte count: Assesses bone marrow response, with low or normal values indicating impaired red cell production. 1
Interpreting Ferritin Based on Inflammatory Status
The ferritin threshold for diagnosing iron deficiency changes dramatically with inflammation:
Without inflammation: Ferritin <30 μg/L confirms iron deficiency. 1, 3
With inflammation: Ferritin up to 100 μg/L may still indicate iron deficiency because ferritin is an acute-phase reactant. 1, 3
Ferritin >150 μg/L: Makes absolute iron deficiency unlikely even with inflammation. 1
Ferritin 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:
Investigate the underlying cause (gastrointestinal bleeding, malabsorption, menstrual losses) and begin oral iron supplementation as first-line therapy. 1
In nondialysis patients without erythropoietic-stimulating agents who lack obvious blood loss, finding iron deficiency should prompt careful assessment for gastrointestinal bleeding. 4
If Iron Studies Are Normal Despite Low MCH/MCHC:
Order hemoglobin electrophoresis—especially in individuals of Mediterranean, African, or Southeast Asian descent—to evaluate for thalassemia trait, which produces microcytosis with low MCH but normal iron parameters. 1
In thalassemia trait, MCV is typically reduced disproportionately to the degree of anemia, and red blood cell count is often elevated. 1
Consider anemia of chronic disease or sideroblastic anemia as alternative diagnoses. 1
If Coexisting Vitamin B12 Deficiency Is Present:
The presence of low vitamin B12 with iron deficiency creates a mixed picture where macrocytic changes from B12 deficiency can be masked by microcytic changes from iron deficiency, potentially resulting in normal MCV despite both deficiencies. 3
Treat vitamin B12 deficiency first to prevent irreversible neurological damage, followed by iron supplementation. 3
Treatment Approach for Confirmed Iron Deficiency
Without active inflammation: Initiate oral iron supplementation with ferrous sulfate 325 mg (65 mg elemental iron) 1-3 times daily between meals, expecting hemoglobin increase of approximately 1-2 g/dL every 2-4 weeks. 1
With active inflammation: Parenteral iron is preferred because systemic inflammation inhibits oral iron absorption. 3
Continue iron supplementation for 3-6 months after hemoglobin normalizes to replenish iron stores, and check hemoglobin, reticulocytes, and iron studies after 4-8 weeks of therapy. 1
Consider parenteral iron if the patient is intolerant to oral iron, has a poor response to oral iron, or has severe anemia requiring rapid correction. 1
Critical 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
Do not dismiss normal ferritin in inflammatory states: Use the higher cutoff of 45-100 μg/L depending on inflammation severity. 1, 3
Do not assume normal MCV excludes B12 deficiency when iron deficiency coexists: The two deficiencies can neutralize each other's effects on MCV. 3
Do not forget to investigate the cause of iron deficiency: It often indicates ongoing blood loss requiring evaluation. 1
Be aware of false MCHC elevation: Cold agglutination and lipemia can cause spuriously elevated MCHC; if MCHC is abnormally high (>37 g/dL), consider technical interference. 5