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REMEDY : BNSSG referral pathways & Joint Formulary

B12 deficiency management and high B12 DRAFT

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B12 deficiency - overview

About B12 deficiency:

  • Clinical features of B12 deficiency are highly variable.

Mildly reduced B12 levels are common and not necessarily a pathological state.

  • Less than 10% of such patients show clinical evidence of deficiency.
  • Deficiency is suggested by:
    • Anaemia and blood film changes
    • Presence of neurological changes consistent with B12 deficiency
    • There is not a reliable correlation between FBC abnormalities and the presence of neurological manifestations.

Who to refer

B12 or folate deficiency does not normally require routine referral for haematology outpatient assessment.

Assessment & Investigations


  • Clinical features to guide clinicians in cases of suspected cobalamin or folate deficiency.


  • Serum vitamin B12 assay
  • Suggested interpretation of serum B12 assay results:

Anti-intrinsic factor antibodies should be tested if pernicious anaemia is suspected regardless of vitamin B12 level. Life-long replacement therapy is indicated.

  • Trial of vitamin B12 if clinical suspicion but indeterminate vitamin B12 levels:
    • Patient wellbeing improves after a couple of days
    • Increased reticulocyte count at 1 week with a normalizing full blood count at 8 weeks
    • Neurology improves after 6-12 weeks.

Special situations:

  • Pregnancy: Vitamin B12 testing should be avoided in pregnancy as results are unreliable (levels naturally decrease in pregnancy). If there is clinical suspicion of deficiency is strong, consider testing but interpret the results with caution. Discussion with the laboratory and additional tests may be needed. An alternative approach may be a short course of therapy and reassessment post-pregnancy.
  • Oral contraceptive pill: Only test if strong clinical suspicion as difficult to interpret vitamin B12 results. Asymptomatic women with mild reduction 145-190ng/l do not need replacement, review diet.
  • Food-B12 malabsorption e.g. gastric acid suppressants or metformin:  only test if strong clinical suspicion. Trial of oral cyanocobalamin could be considered and reviewed at 6 months.


  • Assess and perform relevant investigations before treating macrocytic anaemia or neurological symptoms unless there are features that are well established to be associated with vitamin B12 deficiency.
  • I.M. hydroxycobalamin as per BNF
  • High dose (1000micrograms daily) oral cyanocobalamin may be considered as an alternative. Approximately 1% is absorbed via gastrointestinal tract and is intrinsic factor independent. N.B. When clinical features of vitamin B12 deficiency are present ONLY parenteral replacement is appropriate.
  • A trial of low dose cyanocobalamin 50 micrograms daily can be considered in cases of low vitamin B12 assay results.

High vitamin B12 levels

This is often a non-pathological finding and rarely due to a haematological condition. The most common cause of high vitamin B12 in the absence of B12 replacement therapy is liver disease.  Vitamin B12 may be elevated in haematological malignancy including myeloproliferative disorders and these disorders are excluded by a normal FBC.

Assessment in Primary Care

Check that the patient has not been taking supplements that include vitamin B12.

Assess general health and for risk factors for liver disease.

Investigations in Primary care:

These will be determined by the clinical history examination and blood results. Unless a haematological malignancy is suspected from the FBC report discussion with or referral to Haematology is not required. Assessment for liver disease may be appropriate.



Guidelines for the diagnosis and treatment of cobalamin and folate disorders Vinod Devalia, Malcolm S. Hamilton, and Anne M. Molloy on behalf of the British Committee for Standards in Haematology British Journal of Haematology, 2014, 166, 496–513. Available online at: