Megaloblastic anaemia


Appropriate Tests


Full blood count, Blood film: macrocytosis (may be extreme in severe vitamin deficiency), single, dual or pancytopenia; oval macrocytes, hypersegmented neutrophils). Vitamin B12 and Folate assays.

Elevated Bilirubin and Lactate dehydrogenase are due to haemolysis, including intramedullary haemolysis.

Bone marrow aspiration rarely required to confirm diagnosis.

Review clinical findings to guide investigation of cause.

See also Anaemia

Vitamin B12 deficiency


Folate deficiency



See Folate deficiency, Vitamin B12 deficiency for drugs interfering with absorption.

Inhibition of folate metabolism, especially


  • Methotrexate

Predictable effect.

  • Trimethoprim

In susceptible individuals.

Inactivation of vitamin B12


  • Nitrous oxide

Prolonged exposure, especially anaesthetists.

Inhibition of pyrimidine, purine synthesis, DNA assembly 

Predictable effect.

  • Azathioprine


  • 6-Mercaptopurine


  • 5-Fluorouracil


  • Cytosine arabinoside


  • Cyclophosphamide


  • Zidovudine (AZT)


Inborn errors of metabolism

Rare - consult pathologist.

  • Orotic aciduria


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