British Committee for Standards in Haematology
Summary of Key Recommendations:
• 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.
• Serum cobalamin remains the first line test currently, with additional second line plasma methylmalonic acid to help clarify uncertainties of underlying biochemical/functional deficiencies. Plasma homocysteine may be helpful as a second line test, but is less specific than methylmalonic acid. The availability of these second-line tests is currently limited.
• Serum holotranscobalamin (Active B12-test) has the potential as a first line test, but an indeterminate ‘grey area’ may still exist.
• Definitive cut-off points to define clinical and subclinical deficiency states are not possible, given the variety of methodologies used and technical issues, and local reference ranges should be established.
• In the presence of discordance between the test result and strong clinical features of deficiency, treatment should not be delayed to avoid neurological impairment.
• Treatment of cobalamin deficiency is recommended in line with the British National Formulary. Oral therapy may be suitable and acceptable provided appropriate doses are taken and compliance is not an issue.