Determination of reference values for serum folate and vitamin B12 using three different immunoassays: is it worth making an effort to produce them in our laboratory?

BACKGROUND: Despite being a widely studied concept, the reference interval is the most widely used medical decision-making tool. As such, it is vital that these limits are correctly established and regularly reviewed in the clinical laboratory. METHODS: The reference population comprised 315 healthy individuals selected a priori from Bizkaia province. Blood and serum samples were sent for subsequent assay of vitamin B12 and folate using three immunochemical methods. Reference values were calculated using non-parametric methods. RESULTS: The reference values for serum vitamin B12 and folate were almost identical to those obtained previously using the same methods. Use of new reference values led to an increase in the kappa value despite the low agreement in the case of vitamin B12 (0.4 - 0.62). However, precision obtained for vitamin B12 (94.48 - 96.55%) and folate (95.77 - 97.18%) was very high. The intraclass correlation coefficient ranged from 0.723 to 0.894. Furthermore, a Passing-Bablok regression analysis gave acceptable correlation coefficients of 0.75 - 0.94 for vitamin B12 and 0.92 - 0.95 for folate. CONCLUSIONS: Vitamin B12 and folate deficiencies are currently being over-diagnosed leading to an increase in the number of unnecessary consultations. The main conclusion that can be drawn from our study has resulted in a change in reference values in our laboratory, with a subsequent increase in our ability to accurately detect possible deficiencies. Furthermore, as this study involved all methods currently in use in the Basque healthcare network, its conclusions can be extrapolated to the whole population covered by Osakidetza, thereby improving the rational use of healthcare funding.

Multicentric reference values for some quantities measured with Tina-Quant reagents systems and RD/Hitachi analysers.

Ten clinical laboratories in different regions of Spain have shared the search for reference individuals and the production of reference values for quantities concerning ferritin, transferrin, rheumatoid factors, C-reactive protein and antistreptolysin O, using Tina-Quant reagents systems and RD/Hitachi analysers. All the logistic work has been done in co-operation with the supplier of the reagents and analysers (Roche Diagnostics España, S.L., Barcelona). The reference limits produced in the virtual laboratory are derived from the blend of reference values obtained by each laboratory. The multicentric reference limits were estimated according to the recommendations of the International Federation of Clinical Chemistry. The work done is a model of co-operation between the in vitro diagnostic industry and clinical laboratories for the production of reference values.

Multicentric reference values for some quantities measured with the Elecsys 2010 analyser.

Several clinical laboratories in different regions of Spain have shared the search for reference individuals and the production of reference values for quantities concerning thyrotropin, non-protein bound thyroxine, triiodothyronine, cobalamines and folates, using an Elecsys 2010 analyser. All the logistic work has been done in co-operation with the supplier of the analyser (Roche Diagnostics España, S.L., Barcelona). The reference limits produced in the virtual laboratory are in fact derived from the blend of reference values obtained by each laboratory. The multicentric reference limits were estimated according to the recommendations of the International Federation of Clinical Chemistry. The work done represents a model of co-operation between the in vitro diagnostic industry and clinical laboratories for the production of reference values.