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Vitamin B12 and folate tests: interpret with care

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Clinicians need to consider analytical issues when requesting and interpreting these tests

Vitamin B12 and folate tests are useful for identifying patients with a deficiency. In this issue of the Journal, Willis and colleagues highlight some of the limitations of serum vitamin B12 assays.1 They also emphasise the uncertainty regarding whether red-cell or serum folate should be the preferred first-line test for folate status. The issues underlying some of the data presented require elaboration.

Vitamin B12 assays have an interpretative grey zone in the region of low-normal and mildly low results. Outside the grey zone, the tests show good performance characteristics: a cut-off of 221 pmol/L has a sensitivity of 99%2 and a cut-off of 123 pmol/L has a specificity of 95%.3 Optimal decision points may vary between methods, but results above 220 pmol/L generally rule out deficiency, while results below 125 pmol/L “rule in” deficiency. Between these limits, misclassification may occur if results are interpreted in a binary manner as simply above or below the lower limit of normal (typically about 150 pmol/L). One study used…