What types of anemia commonly cause low Mean Corpuscular Volume (MCV) in a Complete Blood Count (CBC)?

Types of Anemia That Commonly Cause Low MCV in a CBC

Iron deficiency anemia is the most common cause of microcytic anemia (low MCV), followed by thalassemia, anemia of chronic disease, and sideroblastic anemia. 1, 2

Definition and Classification

Microcytic anemia is defined as anemia with a mean corpuscular volume (MCV) less than 80 fL in adults 3. This finding on a Complete Blood Count (CBC) is an important diagnostic clue that narrows down the differential diagnosis to specific types of anemia.

Common Causes of Low MCV

1. Iron Deficiency Anemia

• Most common cause worldwide (approximately 80% of all anemias) 4
• Laboratory findings:
  • Low MCV (<80 fL)
  • Low serum ferritin (<15 μg/L)
  • Low transferrin saturation
  • Elevated RDW (>14.0%)
  • Low serum iron and elevated TIBC 1

2. Thalassemia

• Hereditary disorder of hemoglobin synthesis
• Laboratory findings:
  • Very low MCV (often <70 fL)
  • Normal serum ferritin
  • Normal transferrin saturation
  • Normal RDW (≤14.0%) 5, 1
• The combination of low MCV with normal RDW is particularly useful in distinguishing thalassemia minor from iron deficiency anemia 5

3. Anemia of Chronic Disease (ACD)

• Can present with microcytosis, though typically less severe than iron deficiency
• Laboratory findings:
  • Low or normal MCV
  • Normal or elevated serum ferritin (>100 μg/L)
  • Low transferrin saturation
  • Normal or slightly elevated RDW 1
• Rarely causes severe microcytosis (MCV <70 fL), though cases with MCV as low as 61 fL have been reported 6

4. Sideroblastic Anemia

• Less common cause of microcytic anemia
• Can be inherited or acquired (e.g., lead poisoning, alcohol, certain medications)
• Laboratory findings typically show microcytosis with abnormal iron utilization 3

Diagnostic Approach

When evaluating microcytic anemia, a comprehensive laboratory assessment should include:

• Complete blood count with red cell indices
• Serum ferritin (most specific test for iron deficiency)
• Transferrin saturation
• Red cell distribution width (RDW)
• C-reactive protein (to assess for inflammation) 1

The combination of MCV and RDW is particularly useful:

• Low MCV + High RDW → Iron deficiency anemia
• Low MCV + Normal RDW → Thalassemia minor 5

Clinical Pearls and Pitfalls

• Pitfall: Relying solely on MCV for classification can lead to misdiagnosis. In one study, 16% of patients with microcytic anemia had etiologies that would not be expected based on MCV alone 7
• Pitfall: In inflammatory conditions, ferritin (an acute phase reactant) may be falsely elevated despite iron deficiency. A higher cutoff (up to 100 μg/L) should be used in these cases 1
• Pearl: Response to iron therapy (hemoglobin rise ≥10 g/L within 2 weeks) strongly suggests iron deficiency, even with equivocal iron studies 1
• Pearl: Mixed anemias (e.g., combined iron and B12 deficiency) may present with normal MCV despite underlying deficiencies 7

Special Considerations

• Pregnancy: Iron deficiency is common (up to 84% in third trimester) and requires prompt treatment 1
• Chronic kidney disease: Functional iron deficiency may occur despite normal ferritin levels 1
• Post-bariatric surgery: Patients require regular monitoring for nutritional deficiencies including iron 1
• Thalassemia patients: Should avoid excessive iron supplementation to prevent iron overload 1

Understanding the pattern of laboratory abnormalities, particularly the combination of MCV, ferritin, transferrin saturation, and RDW, is crucial for accurately differentiating between the various causes of microcytic anemia and guiding appropriate treatment.