Interference by vitamin B12-macrocomplexes: towards an effective detection and correct interpretation of hypo- and hypervitaminemia

Abstract Objectives The presence of macro-B12 is a cause of factual hypervitaminemia B12. Precipitation with polyethylene glycol (PEG) is a simple method of removing high-molecular-weight biomolecules. However, “free” molecule may co-precipitate. This fact requires the establishment of reference intervals for the post-precipitation result. The main aims of the study were to: 1) establish post-PEG RIs for vitamin B12; 2) compare the two criteria for defining the presence of macro-B12; 3) evaluate the joint usefulness of percentage post-PEG vitamin B12 recovery and post-PEG RIs to inform the real vitamin B12 status; and 4), propose interpretative comments for ease of interpretation. Methods Prospective study in which 488 serum samples from “healthy” individuals were included and analyzed to determine recovery and RIs following PEG precipitation. Subsequently, a retrospective analysis was carried out in order to evaluate the joint usefulness of both definitions for a suspicion of macro-B12. A total of 297 cases were included. Results Recovery and post-PEG RIs determined on an Alinity i platform ranged from 60 to 107 % and from 118 to 506 pmol/L, respectively. McNemar’s test revealed statistically significant differences between both criteria for estimating interference. However, both methodologies showed good agreement. In 27 cases, the presence of macro-B12 coexisted with true hypervitaminemia B12. No case of coexistence of macro-B12 with vitamin B12 deficiency was detected in our series. Conclusions Laboratory reports should include total vitamin B12 concentration, recovery and post-PEG vitamin B12 concentration with their adjusted RIs to better assess the body vitamin status.