NICE Clinical Knowledge Summaries
Anaemia – B12 and folate deficiency

Last revised in July 2020

B12 Deficiency

  • There is no gold standard test for measuring vitamin B12 deficiency, but the likelihood of deficiency can be determined by measuring serum cobalamin.
    A serum cobalamin of less than 200 nanograms/L is sensitive enough to diagnose 97% of people with vitamin B12 deficiency.
  • Clinical features of vitamin B12 deficiency can occur without anaemia and without low serum levels of vitamin B12.
  • A normal MCV does not exclude the need for cobalamin testing, as neurological impairment occurs with a normal MCV in 25% of cases.
  • Cobalamin levels are not easily correlated with clinical symptoms.

Pernicious Anaemia

  • Pernicious anaemia (an autoimmune disorder which results in reduced production of IF) is the most common cause of severe vitamin B12 deficiency.

  • People with pernicious anaemia may present with symptoms of associated disorders, for example, myxoedema, other thyroid disorders, vitiligo, stomach cancer, or Addison’s disease.

How should I manage people with confirmed vitamin B12 or folate deficiency?

  • If cobalamin levels are low, check for serum anti-intrinsic factor antibodies.
  • Also test people with strong clinical features of B12 deficiency, such as megaloblastic anaemia or subacute combined degeneration of the cord, despite a normal cobalamin level.
  • Anti-intrinsic factor antibody is extremely specific for pernicious anaemia, with a high positive predictive value of 95%, but a low sensitivity of 40–60%. If anti-intrinsic factor antibody is present, pernicious anaemia is very likely, but its absence does not rule out a diagnosis of pernicious anaemia

How should I treat a person with vitamin B12 deficiency anaemia?

For people with neurological involvement
Seek urgent specialist advice from a haematologist.
Ideally, management should be guided by a specialist, but if specialist advice is not immediately available, consider the following:
Initially administer hydroxocobalamin 1 mg intramuscularly on alternate days until there is no further improvement, then administer hydroxocobalamin 1 mg intramuscularly every 2 months.
For people with no neurological involvement
Initially administer hydroxocobalamin 1 mg intramuscularly three times a week for 2 weeks.
The maintenance dose :
Not thought to be diet related — administer hydroxocobalamin 1 mg intramuscularly every 2–3 months for life.

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