Low MCH: Diagnostic Significance and Management
A low Mean Corpuscular Hemoglobin (MCH) indicates hypochromic anemia, most commonly caused by iron deficiency, and requires immediate confirmation with iron studies (serum ferritin and transferrin saturation) followed by investigation of the underlying cause and initiation of oral iron supplementation. 1
What Low MCH Indicates
Low MCH reflects reduced hemoglobin content per red blood cell (hypochromia) and is a more reliable marker of iron deficiency than MCV because it is less dependent on storage conditions and laboratory equipment, and decreases in both absolute and functional iron deficiency. 2
Primary Differential Diagnosis
Low MCH occurs in several conditions that must be distinguished:
- Iron deficiency anemia - the most common cause, characterized by depleted iron stores 2
- Thalassemia - where MCV is typically reduced out of proportion to the degree of anemia 2
- Anemia of chronic disease - particularly when accompanied by inflammation 2
- Sideroblastic anemia - a less common cause requiring bone marrow evaluation 2
The specificity of MCH for iron deficiency is limited, so confirmation with iron studies is mandatory before proceeding with treatment or investigation. 2
Diagnostic Algorithm
Step 1: Confirm Iron Deficiency with Iron Studies
Serum ferritin is the single most specific test for iron deficiency in the absence of inflammation: 2
- Ferritin <15 μg/L - confirms absent iron stores (specificity 0.99) 2
- Ferritin <30 μg/L - indicates low body iron stores in non-inflammatory states 2, 1
- Ferritin <45 μg/L - provides optimal sensitivity-specificity trade-off (specificity 0.92) and warrants consideration of GI investigation, especially with chronic inflammation 2
- Ferritin >150 μg/L - makes absolute iron deficiency unlikely even with inflammation present 2
Add transferrin saturation to the evaluation: 2, 1
- Transferrin saturation <15-16% - confirms iron deficiency 2
- Transferrin saturation <20% - supports iron deficiency diagnosis 1
Step 2: Assess for Inflammation
Check C-reactive protein (CRP) because ferritin is an acute phase reactant that can be falsely elevated in inflammatory conditions. 1 In patients with inflammation, ferritin up to 100 μg/L may still indicate iron deficiency, and the combination suggests both true iron deficiency and anemia of chronic disease. 1
Step 3: Rule Out Alternative Diagnoses
If iron studies are normal despite low MCH, obtain hemoglobin electrophoresis to evaluate for thalassemia, particularly in patients with appropriate ethnic background. 2 This prevents unnecessary gastrointestinal investigation in patients with hemoglobinopathies where MCV is typically reduced out of proportion to anemia severity. 2
Treatment Approach
When Iron Deficiency is Confirmed
Initiate oral iron supplementation as first-line therapy: 1
- Ferrous sulfate 325 mg (65 mg elemental iron) 1-3 times daily between meals 1
- Expect hemoglobin increase of approximately 1-2 g/dL every 2-4 weeks 1
- A good response to iron therapy (Hb rise ≥10 g/L within 2 weeks) is highly suggestive of absolute iron deficiency, even if iron study results are equivocal 2
Continue iron supplementation for 3-6 months after hemoglobin normalizes to replenish iron stores. 1 Check hemoglobin, reticulocytes, and iron studies after 4-8 weeks of therapy to confirm response. 1
Consider parenteral iron if: 1
- Patient is intolerant to oral iron
- Poor response to oral iron occurs
- Severe anemia requires rapid correction
Investigate the Underlying Cause
Investigation should be considered at any level of anemia in the presence of iron deficiency, though the case is stronger with more severe degrees of anemia, as these patients are more likely to have serious underlying GI pathology. 2
In adults with confirmed iron deficiency anemia, investigate for gastrointestinal bleeding or malabsorption as the underlying cause. 1 Fast-track referral is warranted for suspected lower GI cancer when IDA presents with Hb <110 g/L in men or <100 g/L in non-menstruating women, though these cut-offs will miss some cases of colorectal cancer, especially in men. 2
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 for detecting iron deficiency 2, 1
- Do not dismiss normal ferritin in inflammatory states - use the higher cutoff of 45-100 μg/L depending on inflammation severity 2, 1
- Do not forget to investigate the cause of iron deficiency - it often indicates ongoing blood loss requiring evaluation 1
- Do not skip hemoglobin electrophoresis in microcytosis with normal iron studies - this prevents unnecessary GI investigation in patients with thalassemia 2