What is Megaloblastic Anaemia

Megaloblastic anaemia is a disorder of the bone marrow. There is a presence of erythroblasts in the bone marrow with delayed nuclear maturation because of defective DNA synthesis (megaloblasts).

Statistics on Megaloblastic Anaemia

Most common in the elderly with 1 in 8000. It can be seen in all races, but is particularly common in Nordic people. There is an association with other autoimmune diseases, particularly thyroid disease, Addison’s disease and vitilgo.

Risk Factors for Megaloblastic Anaemia

  • Vitamin B12 deficiency;
  • Folic acid deficiency;
  • Conditions with neither B12 nor folate deficiency, e.g. orotic aciduria, where there is a defect in pyrimidine synthesis, therapy with drugs interfering with DNA synthesis and myelodysplasia.

Progression of Megaloblastic Anaemia

  • A deficiency of folate or vitamin B12 may cause megaloblastic anaemia by reducing the supply of the coenzyme methylene tetrahydrofolate.
  • Other congenital and acqiuired forms of megaloblastic anaemia are due to interference with purine or pyrimidine causing an inhibition in DNA synthesis.

How is Megaloblastic Anaemia Diagnosed?

  • A deoxyuridine suppression test can be used to rapidly determine the nature and severity of the vitamin B12 or folate deficiency in severe or complex cases of megaloblastic anaemia.
  • Blood samples will show the typical features of megaloblastic anaemia.
  • Serum bilirubin may be raised as a result of ineffective erythropoeisis.
  • Serum vitamin B12 can be assayed using radioisotope dilution or immunological assays.

Prognosis of Megaloblastic Anaemia

  • Neurological changes if left untreated, can be irreversible.
  • Neuorological abnormalities only occur with very low levels of serum B12.
  • Patients present with symmetrical paraesthesiae in the fingers and toes, early loss of vibration sense and propioception, and progressive weakness and ataxia. Paraplegia may result. Dementia and optic atrophy also occur from vitamin B12 deficiency.

How is Megaloblastic Anaemia Treated?

  • Treatment depends on whether Vitamin B12 or folate deficiency is present.
  • Vitamin B12 deficiency is treated with hydroxycobalamin 1000ug intramuscularly to a total of 5000-6000ug over the course of 3 weeks. 1000ug is then necessary every 3 months for the rest of the patients life.
  • Folate deficiency is treated with 5mg of folic acid daily. Prophylactic folate may be given in pregnancy or in chronic haematological disorders where there is rapid cell turnover.
  • In severely ill patients, it may be necessary to treat with both folic acid an vitamin B12 while awaiting serum levels.

Megaloblastic Anaemia References

  1. Kumar P, Clark M. Clinical Medicine. Fourth Ed. WB Saunders, 2002.