B12 deficiency testing and management (Guideline)

These guidelines are being issued to provide nationally agreed advice for Scotland on appropriate requesting, of B12 testing.  B12 testing is often performed indiscriminately as part of routine screening and can lead to unnecessary diagnostic and management quandaries.  

Cause of Low B12 levels 

• Pernicious anaemia
• vegan diet 
• malabsorption syndromes 
  • coeliac 
  • sprue 
  • chron's 
  • ulcerative colitis (UC) 
  • "food-bound cobalamin malabsorption syndrome" predisposing factors include atrophic gastritis, long term proton pump inhibitor or H2 antagnoist use, chronic alcoholism, gastrectomy/gastric bypass surgery, pancreatic exocrine failure, AIDS 
• myeloma (paraprotein related assay interference) 
• pregnancy 
• combined oral contraceptive pill/HRT 
• pancreatric insufficiency 
• metformin, acute phase situations

1. Mactocytosis (MCV greater than 104.1 on sample processed within 24hours) with or without anaemia 
2. Cytopenias 
3. Unexplained neurological/neuropsychiatric symptoms eg. peripheral neuropathy/sensory ataxia/ambylopia/parasthesia; (newly diagnosed) dementia; visual loss 
4. Oral ulceration/glossitis/"beefy" tongue/angular stomatitis 
5. Malabsorption syndromes as above 
6. Oral B12 therapy 

1. Tiredness is NOT an indication for testing; please check FBC first 
2. Lower B12 levels are seen in patients taking the combined oral contraceptive pill/HRT.  These levels are generally not clinically significant.  Testing should NOT be undertaken in these situations unless one of the indications above is also present.  
3. Low B12 levels, mild macrocytosis and mild thromnbocytopenia (PLT 100 t0 149) are common in pregnancy and usually due to normal physiological changes.  B12 replacement may be considered if PLT less than 100 or unexplained macrocytic anaemia is present (or unexplained paraesthesia or neuropathy) 

If patient is on IM B12 replacement, repeat B12 testing is NOT indicated but FBC and reticulocute response should be monitored.  

• Results out with laboratory normal ranges are flagged on reporting. Note that 2.5% of the population will have results a little below the reference range.
• See Quick Reference Guide for guidance on further advice on interpretation of results and management.
• Intrinsic factor antibodies are positive in only 40 to 60% of cases of pernicious anaemia but with a high specificity. It is not possible to test for the antibody once B12 therapy has commenced.
• Testing for gastric parietal cell antibodies is NOT recommended due to low specificity for the presence of pernicious anaemia.
  Specialised testing for suspected vitamin B12 deficiency is currently under review in Scotland and is not available at this time. Please discuss any specific cases with the haematology department.
• In patients with anaemia, a rise in reticulocytes should be seen by day 7 to 10 of B12 therapy (ensure that the patient also has adequate levels of folate and ferritin).
• Hydroxycobalamin is generally well tolerated. Side effects of the diluent can include itch, exanthema, chills, fever, hot flushes, nausea, dizziness and rarely anaphylaxis. Acneiform eruptions have been reported rarely. Occasionally steroid cover may be required, including hydrocortisone cover in a hospital setting in more severe cases.
• Patients on metformin – use of metformin in type 2 diabetes is associated with low B12 levels. The mechanism is unknown but malabsorption may play a part. This may be alleviated by an increased intake of calcium. It is recommended that B12 levels are checked in patients who have symptoms and signs of deficiency as outlined above. If the B12 level is reduced, check intrinsic factor antibody in case of co-existing pernicious anaemia. If antibody negative and no neurological symptoms, consider a 1 month trial of oral therapy with further monitoring at 6 months and then annually. If antibody positive or neurological symptoms then manage with IM B12 long term.
• Patients on oral contraceptive pill/HRT – as above, testing should only be carried out where there is strong clinical suspicion of symptomatic B12 deficiency. If testing is carried out in the absence of symptoms and the B12 level is mildly reduced (150-200 picogram/mL), further investigation is not likely to be required but review diet and consider oral supplementation. If B12 less than 150 consider alternative cause.
• Pregnancy – as above, testing should only be carried out if there is strong clinical suspicion of symptomatic B12 deficiency. If the B12 level is low, check intrinsic factor antibody. If antibody positive treat long term as for pernicious anaemia. If antibody negative and there is strong clinical suspicion then the recommendation is for 3 injections of IM B12 to cover the pregnancy and then repeat testing at least 2 months post partum if symptoms persist.
• Gastric/bariatric surgery – oral or IM supplementation may be required.
• ‘Food bound cobalamin malabsorption’- consider oral supplementation.
• Long-term therapy where B12 deficiency is due to dietary deficiency: either oral cyanocobalamin tablets 50-150 micrograms daily between meals (adults), or twice yearly hydroxycobalamin injection 1000 micrograms. This may need to be lifelong in vegans.
  In non-vegans, stop once vitamin B12 levels have been corrected and diet has improved, but monitor levels 6 monthly. Advise consumption of foods rich in B12 et. Fortified foods - some soy products, breakfast cereals and breads plus meat, eggs and dairy products.