Vitamin B-12 deficiencyBMJ 2010; 340 doi: http://dx.doi.org/10.1136/bmj.c2305 (Published 01 June 2010) Cite this as: BMJ 2010;340:c2305
- Ben Hudson, senior lecturer
- 1Department of Public Health and General Practice, University of Otago, Christchurch 8140, New Zealand
- Correspondence to:
- Accepted 19 April 2010
An 85 year old man had a preoperative assessment for a knee replacement. His full blood count was normal apart from haemoglobin 95 g/l and mean corpuscular volume 105 fl. He drank no alcohol. Further testing showed that his vitamin B-12 was low: 90 pmol/l (reference range 160-800 pmol/l). Folate, ferritin, thyroid stimulating hormone, and liver function tests were normal. He had no other medical or surgical history and ate a balanced diet that includes meat.
Vitamin B-12 is found only in foods of animal origin. Dietary B-12 is freed from food protein by pepsin in the acid gastric environment and binds to haptocorrin, a protein secreted in saliva. In the small intestine, haptocorrin is degraded by pancreatic enzymes; vitamin B-12 is released and binds with intrinsic factor, which is secreted by gastric parietal cells. This complex binds to receptors at the terminal ileum and is actively absorbed. A small fraction (1-2%) of the intake of B-12 is passively absorbed across the entire absorptive surface of the gastrointestinal tract. The recommended daily allowance of B-12 is small (2 µg per day) in comparison to body stores (2-5 mg).
What you should cover
Assess clinical evidence of B-12 deficiency
Symptoms of B-12 deficiency include neurological changes such as paraesthesia, numbness, ataxia, and memory loss. Oropharyngeal ulceration and glossitis may occur.
Review the medical history and drugs for possible causes (figure)⇓. If suggested by the history, examine for impaired vibration, touch, pain, and position sense and for ataxia.
Review the results of blood testing for macrocytic anaemia and neutrophil hypersegmentation, which indicate B-12 deficiency. Patients may present with neurological changes of B-12 deficiency but with marginal or no haematological abnormalities. Co-existing iron deficiency may prevent the development of macrocytosis in a B-12 deficient patient; if iron deficiency is suspected then check ferritin.
Myelodysplasia may present with macrocytosis and should be suspected if macrocytosis is accompanied by other haematological abnormalities, such as neutropenia, monocytosis, thrombocytopenia, or thrombocytosis. A blood film should be requested and a haematology referral made. Myeloma may also present with macrocytosis and should be considered when bone pain, recurrent infection, or hypercalcaemia are present; serum electrophoresis should be requested.
What you should do
Decide whether your patient has clinical B-12 deficiency
Interpreting B-12 levels is difficult. Concentrations of B-12 vary greatly between individuals and agreement between different commercial assays is poor: patients with clinical deficiency may have “normal” results on some assays and low results on others. Correlation between B-12 concentration and response to B-12 replacement is poor, so although a normal result does not rule out clinical deficiency, a low result does not necessarily indicate the need for treatment. Pregnancy and oral contraceptives can cause low B-12 levels without true deficiency, and patients with underlying haematological disorders may have artificially high levels (myeloproliferative disorders) or low levels (myeloma, severe neutropenia) that do not reflect true stores. Where there is neurological or haematological abnormality and low or borderline low B-12, give a course of treatment and reconsider ongoing replacement if there is no response.
Consider the cause
The first step in clarifying the cause of B-12 deficiency is to check for pernicious anaemia (figure). Intrinsic factor antibodies are highly specific (nearly 100%) but poorly sensitive (about 60%) for pernicious anaemia. Parietal cell antibodies lack specificity, so are less useful. The value of testing where there is a probable cause (gastric surgery or dietary deficiency, for example), or in elderly patients with clear B-12 deficiency, is debated, as treatment is the same regardless of the underlying cause. The Schilling test is no longer widely available.
Refer to a gastroenterologist if malabsorption due to inflammatory bowel disease or coeliac disease is suspected. Pregnant women with B-12 deficiency need urgent haematology advice, as interpreting B-12 levels in pregnancy is particularly difficult and B-12 deficiency is associated with pregnancy complications and birth defects.
Hydroxocobalamin 1 mg by intramuscular injection three times a week for two weeks and then every three months.
Check a full blood count at eight weeks to confirm a return to normal haemoglobin values and cell volume. In anaemia needing urgent confirmation that the cause is B-12 deficiency, a reticulocyte count one week after start of treatment will be markedly raised if B-12 deficiency is the cause. Further monitoring not needed after haematological or symptom response.
Information for patients
Vitamin B12 deficiency anaemia—information and resources on the Patient UK website (www.patient.co.uk/health/Anaemia-(Pernicious)-and-Vitamin-B12-Deficiency.htm)
Pernicious Anaemia Society—international society providing information, help, and support (www.pernicious-anaemia-society.org)
Galloway M, Hamilton M. Macrocytosis: pitfalls in testing and summary of guidance. BMJ 2007;335:884-6. doi:10.1136/bmj.39325.689641.471
Hvas AM, Nexo E. Diagnosis and treatment of vitamin B12 deficiency—an update. Haematologica 2006;91:1506-12.
Cite this as: BMJ 2010;340:c2305
This is part of a series of occasional articles on common problems in primary care. The BMJ welcomes contributions from GPs.
Competing interests : None declared.
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent not required (patient anonymised, dead, or hypothetical).