Vitamin B12 Assays Could Be Missing Anemia

To do so, they used frozen serum samples obtained from 23 untreated pernicious anemia patients (15 with anti-intrinsic factor antibodies and 8 without them). Each patient met five criteria: a low cobalamin level according to a radioisotope-dilution assay, a sufficient volume of the serum used in the radioisotope-dilution assay for additional testing, a clinically expressed cobalamin deficiency, unequivocal proof of pernicious anemia, and a defined anti-intrinsic factor antibody status. Aliquots were tested in three clinical laboratories with the use of different CBLAs.

The results showed that the CBLAs showed false normal values in 6 of 23 (26%), 5 of 23 (22%), and 8 of 23 (35%) serum samples, respectively, as compared with a radioisotope-dilution assay; 5 of the serum samples failed with all three CBLAs. False normal results affected 33%–53% of positive serum samples for anti-intrinsic factor antibodies, but no serum samples that were negative for anti-intrinsic factor antibodies. The activity of anti-intrinsic factor antibodies was nonsignificantly greater in the 9 serum samples with a cobalamin assay error than in the 6 without an error. The study was published on September 6, 2012, as a letter to the editor in the New England Journal of Medicine (NEJM).

“Diagnostic sensitivity of the older microbiologic and radioisotope-dilution assays have been estimated to be about 95%, but since CBLAs have replaced these assays, few studies have compared their sensitivity and specificity with older methods,” concluded study authors Ralph Carmel, MD, and Yash Pal Agrawal, PhD. “The diagnostic failures with all three CBLAs suggest widespread CBLA malfunction. Some speculate that these failures have something to do with the newer tests being unable to inactivate serum anti-intrinsic factor antibodies, which can confound test results.”

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