Characterized by the presence in the bone marrow of erythroblasts with delayed nuclear maturation because of defective DNA synthesis (megaloblasts)

Aetiology

B12 deficiency

• Low dietary intake e.g. veganism
• Pernicious anaemia: autoimmune condition with resulting destruction of gastric parietal cells → results in intrinsic factor deficiency with B12 malabsorption and deficiency
  • Often associated with atrophic gastritis and personal or family history of other autoimmune disorders
  • See autoimmune gastritis
• Other causes include gastrectomy and congenital deficiency of intrinsic factor

Folate deficiency

• Inadequate intake (found in leafy green vegetables)
• Malabsorption
• Excess utilisation - haemolysis, exfoliating dermatitis, pregnancy, malignancy
• Drugs - anticonvulsants

Others

• Drugs
• Rare inherited abnormalities

Pathophysiology

• Megaloblast: an abnormally large nucleated red cell precursor with an immature nucleus
• Megaloblastic anaemias are characterised by a lack of red cells due to predominant defects in DNA synthesis in developing recursor cells (megaloblasts) in the marrow
• In maturing megaloblasts, division is reduced and apoptosis increases
• Cytoplasmic development and haemoglobin accumulation occur normally, and so the precursor cell is bigger with an immature nucleus, i.e. a megaloblast
• Once haemoglobin level in the cell is optimal, the nucleus is extruded, leaving behind a bigger-than-normal red cell, i.e. a macrocyte