What does a decrease in MCV (Mean Corpuscular Volume), MCHC (Mean Corpuscular Hemoglobin Concentration), and MCH (Mean Corpuscular Hemoglobin) indicate?

Interpretation of Decreased MCV, MCHC, and MCH

A simultaneous decrease in MCV, MCHC, and MCH indicates microcytic hypochromic anemia, most commonly caused by iron deficiency anemia, and requires immediate iron studies with serum ferritin as the first diagnostic step. 1, 2

Understanding the Pattern

• Decreased MCV (microcytosis) reflects smaller-than-normal red blood cells, typically occurring when hemoglobin synthesis is impaired 1
• Decreased MCH (hypochromia) indicates reduced hemoglobin content per red blood cell and is considered a more reliable marker of iron deficiency than MCV alone 2
• Decreased MCHC represents the most severe stage of iron deficiency, occurring when hemoglobin concentration falls below 9 g/dL and transferrin saturation drops below 16% 3

The combination of all three parameters being low is particularly significant because MCHC decreases only in advanced iron deficiency, representing the final stage of progressive iron depletion 3

Primary Differential Diagnosis

Iron deficiency anemia is overwhelmingly the most common cause of this pattern 1, 2, 4:

• Serum ferritin <15 μg/L definitively confirms iron deficiency 1
• In the presence of inflammation, consider iron deficiency even with ferritin up to 45 μg/L 1, 2
• Ferritin >100 μg/L essentially rules out iron deficiency even with concurrent inflammation 1

Thalassemia minor presents differently and can be distinguished by:

• Normal RDW (≤14.0%) in thalassemia versus elevated RDW (>14.0%) in iron deficiency 1
• Microcytosis is more pronounced relative to the degree of anemia in thalassemia 1
• Normal or elevated serum ferritin and iron studies in thalassemia 1

Anemia of chronic disease can cause this pattern when prolonged 1, 2

Diagnostic Algorithm

1. Order iron studies immediately with serum ferritin as the single most useful initial test 1, 2

2. Check RDW to help differentiate causes:

   • High RDW (>14.0%) + low MCV strongly suggests iron deficiency 1
   • Normal RDW (≤14.0%) + low MCV suggests thalassemia trait 1

3. Consider additional tests when ferritin is equivocal:

   • Transferrin saturation, serum iron, and total iron-binding capacity 2
   • Note that normal iron studies do not completely exclude iron deficiency in inflammatory states 2

4. Therapeutic trial if diagnosis remains uncertain:

   • Start ferrous sulfate 200 mg three times daily for 2-4 weeks 2
   • A hemoglobin rise of ≥10 g/L within 2 weeks strongly confirms iron deficiency even if iron studies were equivocal 2

Critical Pitfalls to Avoid

• Do not assume normal ferritin excludes iron deficiency in patients with chronic inflammatory conditions, where ferritin may appear falsely normal 1, 2
• Do not give iron supplementation to thalassemia patients without confirming iron deficiency, as unnecessary iron therapy can lead to dangerous iron overload 1
• Do not stop at the CBC - the pattern of decreased MCV, MCH, and MCHC has only moderate diagnostic accuracy (area under ROC curve 0.68-0.96) and cannot definitively diagnose empty iron stores without confirmatory testing 5

Management Based on Cause

For confirmed iron deficiency:

• Initiate oral iron supplementation (ferrous sulfate 200 mg three times daily) 2
• Continue for 3 months total to replenish iron stores if response is positive 2
• Identify and address the underlying cause, particularly gastrointestinal blood loss in adult men and post-menopausal women 1
• In the absence of overt blood loss, perform upper endoscopy with small bowel biopsy and colonoscopy to exclude gastrointestinal malignancy 1

For thalassemia trait:

• Genetic counseling may be appropriate 1
• Specific treatment is usually not required 1

For anemia of chronic disease:

• Focus on treating the underlying inflammatory condition 1