Unwarranted variation in total B12 test thresholds for the diagnosis of vitamin B12 deficiency across the UK and the validation of a method-specific total B12 reference interval for the Beckman Coulter DxI platform to support implementation of NICE N
Emma Stevenson, Rachel Marrington, Duncan Stevenson, Thomas Morris, Finlay MacKenzie, Dominic J. HarringtonAbstract
Background
Prompt diagnosis and treatment of vitamin B12 deficiency prevents haematological, neurological, psychological and psychiatric disturbances. During November 2024, reference interval data used for the clinical interpretation of total B12 assays was collated from participants of the UK NEQAS for Haematinic Assays Scheme. From these data we characterised the geographical variation in diagnostic thresholds across the United Kingdom to identify regions with poor adherence to National Institute for Health and Care Excellence (NICE) guidance (NG239).
Methods
Applied diagnostic thresholds for total B12 were collated from scheme participants and summarised. Because of the reported negative analytical bias of the Beckman DxI total B12 assay in comparison to total B12 assays from Abbott, Roche and Siemens, assay compatibility with NG239 was assessed by deriving a Beckman DxI-specific reference interval using an indirect Hoffman approach applied to 61,117 routine clinical samples.
Results
Diagnostic thresholds for total B12 varied widely across the UK (65–239 ng/L; 48–176 pmol/L). Only 16.6 % of laboratories used the NG239 best-practice threshold of 180 ng/L (133 pmol/L). The Beckman DxI total B12 assay was not compatible with the NG239 cut-off; a lower threshold, such as a locally derived cut-off or the manufacturer’s recommended 145 ng/L (107 pmol/L), was indicated for this platform.
Conclusions
Substantial national heterogeneity in applied total B12 diagnostic thresholds persist, with limited adoption of NG239 guidance. Platform-related analytical bias undermines the use of universal decision limits. For Beckman DxI, use of a platform-appropriate threshold is required to support clinically consistent diagnosis of vitamin B12 deficiency.