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Clinical Review

ABC of clinical haematology: Macrocytic anaemias

BMJ 1997; 314 doi: (Published 08 February 1997) Cite this as: BMJ 1997;314:430
  1. Victor Hoffbrand,
  2. Drew Provan


    Macrocytosis is a rise in the mean cell volume of the red cells above the normal range (in adults 80-95 fl (femtolitres). It is detected with a blood count, in which the mean cell volume, as well as other red cell indices, is measured. The mean cell volume is lower in children than in adults, with a normal mean of 70 fl at age 1 year, rising by about 1 fl each year until adult volumes are reached at puberty.

    Megaloblastic bone marrow is exemplified by developing red blood cells that are larger than normal, with nuclei more immature than their cytoplasm. The underlying mechanism is defective DNA synthesis

    Causes of megaloblastic anaemia


    Vitamin B12 deficiency–Veganism, poor quality diet

    Folate deficiency–Poor quality diet, old age, poverty, synthetic diet without added folic acid, goats' milk


    Gastric causes of vitamin B12 deficiency–Pernicious anaemia, congenital intrinsic factor deficiency, gastrectomy

    Intestinal causes of vitamin B12 deficiency–Stagnant loop, congenital selective malabsorption, ileal resection

    Intestinal causes of folate deficiency–gluten induced enteropathy, tropical sprue

    Increased cell turnover

    Folate deficiency–Pregnancy, prematurity, chronic haemolytic anaemia (such as sickle cell anaemia), inflammatory and malignant diseases

    Renal loss

    Folate deficiency–Congestive cardiac failure, dialysis


    Folate deficiency–Anticonvulsants, sulphasalazine

    Defects of vitamin B12 metabolism–for example, transcobalamin II deficiency, nitrous oxide anaesthesia–or of folate metabolism (such as methotrexate treatment), or rare inherited defects of DNA synthesis may all cause megaloblastic anaemia

    The causes of macrocytosis fall into two groups: (a) deficiency of vitamin B12 (cobalamin) or folate (or rarely abnormalities of their metabolism) in which the bone marrow is megaloblastic and (b) other causes, in which the bone marrow is usually normoblastic. In this article the two groups are considered separately, and then the reader is taken through the steps to diagnose the cause of macrocytosis and its management.

    Deficiency of vitamin B12 or folate

    Vitamin B12 deficiency

    The body's requirement for vitamin B12 is …

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