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Investigations in pernicious anaemia

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

  • FBC - macrocytic anaemia, may show neutropaenia and thrombocytopenia

  • peripheral blood film shows anisocytosis, poikilocytosis

  • low serum vitamin B12; normal folate

  • serum bilirubin may be increased because of haemolysis

  • bone marrow shows features of megaloblastic erythropoiesis

  • detection of autoantibodies:
    • parietal cells - serum (95%), gastric juice (70%)
    • intrinsic factor - serum (50-60%), gastric juice (85%)
    • detection of serum antibodies is usually performed for convenience; only those to IF are diagnostic
    • presence of intrinsic factor antibodies in serum
      • positive in 50-60% of patients with pernicious anaemia (1)
      • the presence of intrinsic factor (IF) is diagnostic of pernicious anaemia but negative intrinsic factor antibodies does not exclude pernicious anaemia (due to the test’s low sensitivity (50-60%)) - gastric parietal cell (GPC) antibodies are seen in 95% of cases of pernicious anaemia and, although there is an overlap with other autoimmune diseases and with normal individuals, a negative result makes pernicious anaemia unlikely (1)
      • a positive anti-GPC and/or anti-IF antibody test does need repeating (3)

Other investigations include absorption tests - Schilling test (very rarely undertaken now) - and gastrointestinal investigations.


  1. Pulse 2004; 64(35):88.
  2. NHS Wiltshire CCG. Investigation and treatment of Vitamin B12 (cobalamin) deficiency in primary care
  3. Royal United Hospital Bath NHS Trust. Guidelines for the Investigation & Management of vitamin B12 deficiency (accessed 25/4/2020).
  4. Mohamed M et al. Pernicious anaemia. BMJ 2020;369:m1319.


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