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NHS FORTH VALLEY
B12 and Folate: A Practical Guide
Date of First Issue
27/05/2011
Approved
28/06/2011
Current Issue Date 24/06/2013
Review Date
24/06/2015
Version
1.0
EQIA
27/05/2011
Author / Contact
Dr Roddy Neilson
Group Committee –
Final Approval
Primary Care Prescribing Group 28/06/2011
Laboratory Clinical Governance Group 22/06/2011
This document can, on request, be made available in alternative formats
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NHS Forth Valley
Consultation and Change Record
Contributing Authors:
Dr Lucy Munro,
GP Principal and Associate
Advisor (cpd) in consultation with:
Dr Roddy Neilson Consultant Haematologist
Dr Chris Brammer Consultant Haematologist,
Dr Gillian McLean Consultant Psychiatrist,
Dr Chris Neumann Consultant Neurologist,
Dr Peter Bramley
Consultant Gastroenterologist
Development was supported by NHS FV Quality Improvement
Services
Consultation Process:
This guide was written with significant input from Drs Neilson
and Brammer Consultant Haematologists and drew heavily
from the Laboratory Handbook.
Dr G McLean Consultant in Old Age Psychiatry, Dr C
Neumann, Consultant Neurologist and Dr P Bramley,
Consultant Gastroenterologist also provided input and agreed
the final version.
Dr Leslie Cruickshank Prescribing Advisor was consulted.
Pharmacy has also been consulted.
Distribution:
All GP practices to be sent hard copies in the Whole Systems
Working Folder
Change Record
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B12 AND FOLATE: A Practical Guide
Testing ►
The main reasons to test B12 and Folate levels are;
Neuropsychiatric symptoms where the cause is not known; B12 deficiency is a rare cause of peripheral neuropathy, dementia, myelopathy and can cause sub acute combined
degeneration of the spinal cord
Macrocytosis (MCV > 100) or Macrocytic Anaemia; in pregnancy/while taking COCP an MCV up to 105 is usually a normal finding and does not require investigation
Other circumstances where higher vigilance is needed and testing of B12 and Folate assays may be indicated;
Previous gastric surgery /Inflammatory Bowel Disease/Coeliac Disease these patients are at higher risk of B12 and Folate deficiency and may require B12 and Folate testing particularly if their symptoms are severe/there is a macrocytosis or anaemia/there are neuropsychiatric symptoms although remember azathioprene and mecaptopurine can both cause macrocytosis Iron deficiency anaemia not responding to adequate oral iron in a simple iron deficiency
anaemia a rise of in HB 1g/dl/wk or 2g/dl/3 wks would be expected, B12 and folate deficiency are possible although rare causes of failure to respond to oral iron
Circumstances NOT to check B12 and Folate levels;
o There is no value in re-testing B12 levels in patients who are already on parenteral vitamin B12, when required, use FBC to monitor response to B12 injections
o Some medications, such as metformin and COCP, can reduce B12 absorption but taking these medications is not of itself an indication to check B12/folate levels
o Non specific tiredness is not an indication to check B12/Folate levels in the absence of other indications
Interpreting the results B12 ►
B12 <120 is not normal, it is low and most likely to be pathologically low warranting further investigation (severe dietary deficiency can sometimes occur to this level in longstanding dementia patients and vegans)
B12 120-180 is borderline and management will depend upon the clinical situation B12 > 180 is normal
Management of B12 results ►
B12 < 120: this is low
• Check Anti Intrinsic Factor antibodies PRIOR to treatment • Anti-IF antibodies are diagnostic of Pernicious Anaemia
• Schilling tests are no longer available and anti gastric parietal cell antibodies are non specific and non diagnostic
• Negative Anti-IF antibodies does not exclude Pernicious Anaemia and in the absence of history or examination findings suggestive of terminal illeal disease or another cause of B12 deficiency a presumptive diagnosis of Pernicious Anaemia can be made
• The diagnosis of Pernicious Anaemia means that the patient will require lifelong treatment with parenteral B12
• Dietary deficiency can occasionally cause levels this low but only when the diet is deficient in B12 over a prolonged period such as in dementia or veganism. Take a dietary history. B12 120 -180: this is a borderline result
• Check Anti-IF antibodies PRIOR to treatment
• Anti-IF antibodies are diagnostic of Pernicious Anaemia
• Otherwise management of B12 at these levels is dependent upon the clinical situation. • It is a normal finding in some patients
• Use Clinical judgement depending upon the situation Consider the patient’s clinical situation: Examples
o Does the patient have myelopathy/peripheral neuropathy? Treat pragmatically with parenteral B12
o Does the patient have dementia? It is most likely that the deficiency is dietary and can be very severe depending upon the length of time the patient’s diet has been sufficiently poor. Unless the patient has Pernicious Anaemia the aim is the return to a better nutritional status rather than defaulting to lifelong B12 injections. The evidence suggests that replacement of B12 does NOT reverse cognitive impairment but a return to a better general nutritional status is best practice. Short term B12 injections may be needed
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o Is the patient anaemic with a macrocytosis? treat pragmatically with B12
o Take a dietary history. Is the patient a vegan? Oral B12 replacement (SLS) may be needed. o Does the patient have symptoms suggestive of terminal illeal disease? These patients may require onward referral
o Does the patient have other auto immune disorders or a strong family history of auto immune disorders? > consider watchful waiting/monitoring of B12 levels 6 monthly
B12 >180: this is normal, no action required
Treatment for B12 deficiency ►
What and how?
• The treatment for Pernicious Anaemia is parenteral B12 (Hydroxocobalamin) (patients with Pernicious Anaemia cannot absorb oral B12)
• Oral B12 (Cyanocobalamin) replacement is not well absorbed in ANY patient and as such requires very large doses
• In those with dietary deficiency, return to normal nutritional status is preferable where possible. Short term parenteral B12 may be needed in patients with dementia. The evidence for the use of oral B12 is not clear but is likely to have a place in ongoing dietary deficiency e.g. veganism (script should be marked SLS)
• Parenteral B12 is often the ‘default’ treatment option because not all PA can be confirmed. See below for advice on additional folic acid replacement
How often?
• The BNF loading schedule for B12 should be followed and patients should then be given B12 injections 3 monthly
• If there are neurological features present then the situation is different; the BNF loading schedule should be followed then B12 should be given every 2 months
In the absence of neurological features or anaemia there is no value to administering parenteral B12 injections any more often than 3 monthly. For those occasional who wish to have more frequent B12 injections this is not driven by low B12 levels.
There is no value in re testing B12 levels in those already receiving parenteral B12, monitoring can be done with FBC alone.
The Role of Folate ►
Serum folic acid assays reflect recent dietary habits.
Red Cell Folate is a more reliable indicator of the actual total body folate status but a considerably more difficult to test to do and as such is reserved for those with borderline serum folate results.
Diet is the commonest cause of low folate levels and a six week course of folic acid is the most
appropriate course of action in the first instance. Ideally thereafter dietary correction should take place. If there are symptoms suggestive of small bowel disease or if there is a poor response to oral folate then further investigation for small bowel disease is required.
Secondary folate deficiency is often seen as a consequence of B12 deficiency – in this situation patients often require folic acid and B12.
Moderate B12 deficiency may occur secondary to severe folate deficiency – B12 replacement in this situation may only be needed until folate stores are repleted
When to refer/discuss with
Secondary Care ►
• Haematology: Failure to respond to therapy. Some haematological problems such as
myelodysplasia may present in a similar fashion to pernicious anaemia and as such if there is a failure to respond to B12 therapy i.e. there is not a prompt rise in HB. This situation should be discussed with a haematology consultant
• Gastroenterology: Suspected malabsorption/terminal illeal disease, consider discussion with or referral to gastroenterology
• Neurology: If there is a peripheral neuropathy which fails to respond to standard treatments, consider discussion with or referral to neurology
Dementia: B12 deficiency usually has a dietary cause in patients dementia but parenteral B12 may be required if there is anaemia, pernicious anaemia or neurological symptoms.
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Resources
Haematology & Blood Transfusion Laboratory Handbook, Forth Valley.
Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Library 2005. Vitamin B12 for cognition. Malouf R, Areosa Sastre A. Cochrane Library 2003
NHS Clinical Knowledge Summaries Clinical topic - Anaemia - B12 and folate deficiency BNF March 2011
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