Macrocytic anaemia and megaloblastic anaemia

Macrocytic anaemia is a form of anaemia characterised by macrocytosis (MCV > 100 fL).

Megaloblastic anaemia is the most common subtype of macrocytic anaemia characterised by decreased DNA synthesis in haematopoietic stem cells, causing RBCs to be larger, oval, and blast-like, and neutrophils to be hypersegmented. The most common cause of megaloblastic anaemia is folate and B12 deficiency.

Etiology

• Megaloblastic anaemia
  • B12 deficiency
    • Insufficient intake
    • Pernicious anaemia
    • Crohn disease
    • Small bowel resection
  • Folate deficiency
    • Insufficient intake
    • Alcoholism
  • Drugs that block DNA synthesis (methotrexate)
  • Myelodysplasia
• Non-megaloblastic macrocytic anaemia
  • Liver disease
  • Alcoholism

Clinical features

General features of anaemia are present.

In severe B12 deficiency, cell lines other than the RBC may be affected as well, potentially causing pancytopaenia. It may also lead to demyelination of the spinal cord, also called funicular myelosis or subacute combined degeneration of the spinal cord, which may lead to ataxia and decreased proprioception and vibration sense.

Diagnosis and evaluation

In case of macrocytic anaemia, a blood smear should be made to look for megaloblastic changes.

If the macrocytic anaemia is megaloblastic, serum folate and B12 levels can be measured. Serum homocysteine and methylmalonic acid (MMA) can also be measured to differentiate between B12 and folate deficiency:

• B12 deficiency: Elevated homocysteine and methylmalonic acid levels,
• Folate deficiency: Elevated homocysteine levels, normal methylmalonic acid

If there is deficiency, the underlying cause should be sought. Testing for anti-parietal cell or anti-IF antibodies can diagnose pernicious anaemia.

Treatment

Treatment is targeted at the underlying cause, if possible. If not, supplements might necessary. B12 deficiency is ideally treated with intramuscular injections rather than oral therapy, as oral absorption of B12 supplements is poor.

If a patient is suffering from B12 deficiency but given folate supplements, the surplus folate can normalise the megaloblastic anaemia, giving a false impression that they had folate deficiency. However, folate does not stop the progression of and can even worsen B12 deficiency-induced spinal cord degeneration, which can be irreversible. It’s therefore important to confirm that B12 levels are normal before administering folate supplements.