Anaemia characterised by large red blood cells. Usually due to folate and/or vitamin B12 deficiency. Some medicines
(hydroxyurea, zidovudine, stavudine can cause macrocytic anaemia without folate and/or vitamin B12 deficiency).


  • Low dietary intake of folate/increased need (e.g., children, pregnancy)
  • Low dietary intake of vitamin B12 (in exclusively vegetarian diets, without any animal proteins)
  • Malabsorption of folate and vitamin B12 (severe gastritis, giardia infection, severe intestinal diseases)
  • Medicines e.g., metformin, zidovudine, hydroxyurea, stavudine, phenytoin
  • Other causes of macrocytosis: myelodysplasia, hypothyroidism, chronic alcohol use, multiple myeloma

Clinical features

  • General anaemia signs
  • Vitamin B12 deficiency: neuropsychiatric abnormalities e.g., impaired vibration and position sense, abnormal gait, weakness, decreased muscle strength, spastic motions, memory loss, disorientation, depression, and acute
    confusional state


  • Blood smear: macrocytosis
  • Elevated MCH/MCV
  • Pancytopenia in severe cases
  • Full blood count: oval macrocytes, hypersegmentation of neutrophils, thrombocytopenia
  • Decreased serum Vitamin B12 or red cell folate


General measures

  • Identify and treat underlying cause of anaemia
  • Dietary modifications to ensure adequate intake of folate and vitamin B12, e.g., eat plenty of green
    leafy vegetables, and/or food of animal origin

Folic acid and vitamin B12 supplementation

  • Folic acid: 5 mg daily until haemoglobin levels return to normal
  • Vitamin B12: 1 mg IM daily for 5 days; then weekly for a further 3 doses
    • Follow with 1 mg every second month for life in patients with pernicious anaemia
  • If vitamin B12 deficiency is suspected: (low leucocytes and platelets, neuropsychiatric symptoms, vegan diet)
    DO NOT GIVE folic acid alone but refer for further testing and treatment. Giving folic acid alone in
    patients with B12 deficiency may precipitate permanent neurological deficit.
  • Anaemia normally corrects within 1-2 months. White cell count and thrombocytopenia normalise within 7-10
  • DO NOT use ferrous-folate combination tablets to treat folic deficiency because the quantity of folic acid is too