22nd May 2023

Macrocytic anaemia

Macrocytosis is defined as an MCV>100fL, and when associated with anaemia is termed macrocytic anaemia. It can be subdivided into megaloblastic and non-megaloblastic anaemia.

Megaloblastic anaemia

Megaloblastic anaemia is named due to the presence of enlarged, immature red blood cells (megaloblasts) and hypersegmented neutrophils on blood film. This results from impaired DNA synthesis or maturation during red blood cell production, which delays the progression of the cell cycle from the G2 growth stage to mitosis, leading to continuing cell growth and enlarged red blood cells.

Causes of megaloblastic anaemia can be divided into those resulting in vitamin B12 deficiency and folate deficiency.

Common causes of vitamin B12 deficiency include:

• Pernicious anaemia – autoimmune destruction of gastric parietal cells causing reduced production of intrinsic factor, a glycoprotein required for B12 absorption in the terminal ileum.
• Post-gastrectomy or post-terminal ileum resection e.g. due to Crohn’s disease
• Proton-pump inhibitors e.g. omeprazole
• Bacterial overgrowth
• Decreased intake e.g. vegan diet without vitamin B12 supplementation

Common causes of folate deficiency include:

• Decreased intake e.g. alcohol dependence, elderly, anorexia nervosa
• Decreased absorption e.g. coeliac disease
• Increased demand e.g. pregnancy, malignancy, chronic inflammation
• Excessive urination e.g. in congestive heart failure or dialysis
• Drugs e.g. phenytoin, methotrexate, trimethoprim, sulfasalazine, cholestyramine

Non-megaloblastic anaemia

Non-megaloblastic anaemias (also known as normoblastic anaemias) comprise other causes of macrocytosis without impairment of DNA synthesis. Therefore, megaloblasts and hypersegmented neutrophils do not feature on the blood film in non-megaloblastic anaemia.

Causes of non-megaloblastic anaemia include:

• Alcohol excess
• Reticulocytosis – reticulocytes are large, immature red cells. Reticulocytosis can be seen when there is increased bone marrow activity to replace red blood cell loss, such as in haemolysis or haemorrhage.
• Liver disease
• Hypothyroidism
• Tyrosine-kinase inhibitors e.g. imatinib
• Myelodysplasia
• Multiple myeloma