Healthcare Professionals Information

British Committee for Standards in Haematology Guideline on Cobalamin and Folate Disorders

The Guideline acknowledges the problems with the current front-line Serum B12 test and the Intrinsic Factor Antibody assay.

Key Recommendations for diagnosing B12 Deficiency

  • The clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status since there is no ‘gold standard’ test to define deficiency.
  • Definitive cut-off points to define clinical and subclinical deficiency states are not possible, given the variety of methodologies used and technical issues.
  • Neurological symptoms due to cobalamin deficiency may occur in the presence of a normal MCV/Hb.
  • Plasma tHcy and/or plasma MMA, depending on availability, may be considered as supplementary tests to determine biochemical cobalamin deficiency in the presence of clinical suspicion of deficiency but an indeterminate serum cobalamin level.
  • Serum cobalamin level of greater than 148 pmol/L (200 ng/l) in the presence of a strong clinical suspicion of cobalamin deficiency should be evaluated further with MMA, tHcy or HoloTC and a trial of hydroxocobalamin given to ascertain any clinical improvement.

Key Recommendations for diagnosing Pernicious Anaemia

  • All patients with anaemia, neuropathy or glossitis, and suspected of having pernicious anaemia, should be tested for anti-intrinsic factor antibody regardless of cobalamin levels.
  • Patients found to have a low serum cobalamin level in the absence of anaemia, and who do not have food malabsorption or other causes of deficiency, should be tested for IFAB to clarify whether they have an early/latent presentation of pernicious anaemia.
  • Patients found to be positive for intrinsic factor antibodies should have lifelong therapy with cobalamin.
  • Patients negative for intrinsic factor antibody, with no other causes of deficiency, may still have pernicious anaemia as a result of poor sensitivity of the test and should be treated as anti-intrinsic factor antibody negative pernicious anaemia. Lifelong therapy should be continued in the presence of an objective clinical response.

Key Recommendations for the Treatment

  • Treatment of cobalamin deficiency is recommended in line with the British National Formulary:
    By intramuscular injection:

    • Without neurological involvement: Initially 1 mg 3 times a week for 2 weeks, then 1 mg every 2–3 months.
    • With neurological involvement: Initially 1 mg once daily on alternate days until no further improvement, then 1 mg every 2 months.
  • Measuring cobalamin levels is unhelpful as levels increase with treatment regardless of how effective it is. (NICE Clinical Knowledge Summaries)

Pernicious Anaemia Priority Setting Partnership Survey

The PAS has formed a PSP with the James Lind Alliance to identify uncertainties relating to the way in which PA is diagnosed and treated. Let us know what questions you want research to answer in this short survey:
or find out more here

Treating Pernicious Anaemia and the current COVID-19 pandemic - A Guide for Doctors

The Pernicious Anaemia Society is fully supportive of any measures taken to reduce the risk of health care professionals contracting the Covid-19 virus. The Guideline balances the need for patients to receive their parenteral replacement therapy injections whilst reducing the risk to front-line staff of cross-infection.

When to test (serum) B12?

  • Macrocytic anaemia
  • Neurological/neuropsychiatric symptoms: paresthesia, aphasia, ataxia, sensory loss, dementia, psychosis, paranoia, depression, mood swings, behavioural changes, etc
  • Symptoms as glossitis, extreme fatigue, loss of appetite, see more
  • Diabetes, Auto-immune thyroid disease, Crohn’s disease, MS, pancreatic insufficieny, gastric bypass, coeliac disease
  • Use of medication : metformin, ppi’s, Questran, colchicine
  • Vegan/strict vegetarian diet

Further Information


Guidelines on Cobalamin and Folate issued by the British Committee for Standards in Haematology


NICE Management of anaemia - vitamin B12 and folate deficiency


Videos/documentaries about PA/B12 deficiency including from our Conferences on Pernicious Anaemia

Contact us for specific information, we will be happy to advise you or put you in contact with a medical professional that can help with specific problems

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Application to become a Healthcare Affiliate Member of the Pernicious Anaemia Society

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