What are the causes of decreased hemoglobin (Hb) with reduced mean corpuscular volume (MCV)?

Causes of Decreased Hemoglobin with Reduced MCV

The primary causes of decreased hemoglobin with reduced mean corpuscular volume (MCV) include iron deficiency anemia, thalassemias, anemia of chronic disease, sideroblastic anemia, and lead poisoning, with iron deficiency being the most common etiology. 1

Major Causes of Microcytic Anemia

1. Iron Deficiency Anemia

• Most common cause of microcytic anemia worldwide 1, 2
• Characterized by:
  • Low serum ferritin (<30 μg/L in non-inflammatory states) 1
  • Low transferrin saturation (<15%) 1
  • Elevated RDW (>14.0%) 1
  • Progressive reduction in hemoglobin synthesis
• Common etiologies:
  • Gastrointestinal blood loss (most common in adult men and post-menopausal women) 1
  • Menstrual blood loss (most common in pre-menopausal women) 1
  • Malabsorption (e.g., celiac disease, gastric bypass) 1
  • Poor dietary intake 1
  • NSAID use causing GI bleeding 1

2. Thalassemias

• Hereditary disorders of globin chain synthesis 1, 3
• Characterized by:
  • Disproportionately low MCV relative to hemoglobin level 1
  • Normal or elevated RBC count 4
  • Normal or low RDW (≤14.0%) 1
  • Normal or elevated iron studies 4
  • Hemoglobin electrophoresis abnormalities 1
• More common in certain ethnic groups (Mediterranean, Middle Eastern, Asian) 1

3. Anemia of Chronic Disease/Inflammation

• Associated with chronic inflammatory conditions, infections, malignancies 1
• Characterized by:
  • Mild to moderate microcytosis 1
  • Elevated inflammatory markers (CRP, ESR) 1
  • Normal to elevated ferritin (30-100 μg/L may still indicate iron deficiency in inflammatory states) 1
  • Low transferrin saturation 1
  • Functional iron deficiency due to hepcidin upregulation 1

4. Sideroblastic Anemia

• Group of disorders with defective heme synthesis 3
• Can be hereditary or acquired (alcohol, lead, drugs, myelodysplastic syndrome) 1
• Characterized by:
  • Presence of ring sideroblasts in bone marrow 1
  • Elevated serum iron and ferritin 1
  • Variable RDW

5. Lead Poisoning

• Rare cause of microcytic anemia 1
• Characterized by:
  • Elevated blood lead levels
  • Basophilic stippling of RBCs
  • Elevated erythrocyte protoporphyrin 1

Diagnostic Approach

1. Initial Assessment:

   • Complete blood count with RBC indices
   • Peripheral blood smear examination
   • Reticulocyte count to assess bone marrow response 1

2. Iron Studies:

   • Serum ferritin (most specific test for iron deficiency) 1
   • Transferrin saturation
   • Serum iron and TIBC 1

3. Additional Testing Based on Clinical Suspicion:

   • Hemoglobin electrophoresis if thalassemia suspected 1
   • Inflammatory markers (CRP, ESR) if anemia of chronic disease suspected 1
   • Lead levels if lead poisoning suspected
   • Bone marrow examination if sideroblastic anemia suspected 1

Differential Diagnosis Using RDW and Other Parameters

• High RDW + Low MCV: Suggests iron deficiency anemia 1
• Normal RDW + Low MCV: Suggests thalassemia trait 1
• Low MCV + Normal/High Reticulocyte Count: Suggests hemoglobinopathies 1
• Low MCV + Low Reticulocyte Count: Suggests iron deficiency, anemia of chronic disease, or lead poisoning 1

Special Considerations

• In inflammatory states, ferritin up to 100 μg/L may still be consistent with iron deficiency 1
• Combined deficiencies (e.g., iron deficiency with folate or B12 deficiency) may result in a normal MCV despite iron deficiency 1
• Hodgkin's disease can cause microcytic anemia through unbalanced globin chain synthesis 5
• Certain malignancies can present with microcytic anemia before other symptoms appear 1

Remember that proper identification of the cause of microcytic anemia is essential for appropriate treatment and to avoid missing underlying serious conditions such as gastrointestinal malignancies.