Healthcare Professionals Information

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

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)