Analysis of annual distributions of hemoglobin A2 values as a method to test for HbA2 standardization

Matteo Vidali; Renata Paleari; Ferruccio Ceriotti; Sergio Bernardini; Ilio Giambini; Duilio Brugnoni; Laura Trainini; Ciriaco Carru; Filippo Porcu; Mariarosa Carta; Davide Giavarina; Marcello Ciaccio; Bruna Lo Sasso; Gaetano Corso; Carmela Paolillo; Romolo Dorizzi; Marco Rosetti; Marcello Fiorini; Maria Bombara; Michela Grosso; Mariarosaria Giuliano; Massimo Locatelli; Antonella Lucci; Francesca Mencarelli; Novella Scattolo; Marta Strollo; Andrea Mosca

doi:10.1016/j.cca.2023.117564

Analysis of annual distributions of hemoglobin A₂ values as a method to test for HbA₂ standardization

Clin Chim Acta. 2023 Oct 1:550:117564. doi: 10.1016/j.cca.2023.117564. Epub 2023 Sep 23.

Authors

Matteo Vidali¹, Renata Paleari², Ferruccio Ceriotti¹, Sergio Bernardini³, Ilio Giambini³, Duilio Brugnoni⁴, Laura Trainini⁴, Ciriaco Carru⁵, Filippo Porcu⁶, Mariarosa Carta⁷, Davide Giavarina⁷, Marcello Ciaccio⁸, Bruna Lo Sasso⁹, Gaetano Corso¹⁰, Carmela Paolillo¹⁰, Romolo Dorizzi¹¹, Marco Rosetti¹¹, Marcello Fiorini¹², Maria Bombara¹³, Michela Grosso¹⁴, Mariarosaria Giuliano¹⁴, Massimo Locatelli¹⁵, Antonella Lucci¹⁶, Francesca Mencarelli¹⁷, Novella Scattolo¹⁸, Marta Strollo¹⁹, Andrea Mosca²⁰

Affiliations

¹ Clinical Pathology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
² Dept. of Physiopathology and Transplantation, Università degli Studi di Milano, Milano, Italy.
³ Dept. of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
⁴ Clinical Chemistry Central Laboratory, Diagnostic Department, Spedali Civili of Brescia, Brescia, Italy.
⁵ Dept. of Biomedical Sciences, University of Sassari and Hospital University of Sassari (AOUSS), Sassari, Italy.
⁶ Laboratory of Clinical Pathology Unit of Azienda Ospedaliero Universitaria, Hospital University of Sassari (AOUSS), Sassari, Italy.
⁷ Laboratory Medicine, Diagnostic Dept., St. Bortolo Hospital, Vicenza, Italy.
⁸ Dept. of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Clinical Laboratory Medicine, University of Palermo, Palermo, Italy.
⁹ Dept. of Laboratory Medicine, University Hospital "P. Giaccone", Palermo, Italy.
¹⁰ Dept. of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
¹¹ Clinical Pathology Unit, Hub Laboratory, AUSL della Romagna, Cesena, Italy.
¹² Clinical Pathology Laboratory, Azienda Ospedaliero-Universitaria Senese, Siena, Italy.
¹³ Clinical Chemistry Laboratory, Ambito Territoriale Livorno, Azienda USL Toscana Nord Ovest, Livorno, Italy.
¹⁴ Dept. of Molecular Medicine and Medical Biotechnology, Università degli Studi di Napoli Federico II, Napoli, Italy.
¹⁵ Laboratory Medicine Service, IRCCS San Raffaele Hospital, Milano, Italy.
¹⁶ Santa Maria Goretti Hospital, Latina, Italy.
¹⁷ Clinical Pathology and Hematology Service, Azienda Ospedaliera di Perugia, Perugia, Italy.
¹⁸ Central Laboratory, Ospedale S. Bonifacio, ULSS 9 Scaligera, Verona, Italy.
¹⁹ Laboratory of Clinical Pathology, ASST dei Sette Laghi, Varese, Italy.
²⁰ Dept. of Physiopathology and Transplantation, Università degli Studi di Milano, Milano, Italy. Electronic address: andrea.mosca@unimi.it.

PMID: 37748747
DOI: 10.1016/j.cca.2023.117564

Abstract

Background and aims: The monitoring of yearly distributions of HbA₂ measured has been indicated as a reliable indicator of worldwide standardization.

Materials and methods: Measurements/year of HbA₂ have been collected over three consecutive years in 15 Italian laboratories each using the same analytical method over three years period. HbA₂ distributions, cleaned of replicated measurements, were compared by the overlapping area of the raw probability density functions expressed by coefficient eta (η), and by comparing the reference intervals for the central part of each distribution estimated by the indirect method refineR using the R package "refineR".

Results: According to the overlapping areas analysis the distributions/year of the data provided by 4 centers able to perform at least 1000 measurements/year were similar in 2 consecutive years. Moreover, the reference intervals provided by 2 centers using the same analytical methods in two separate locations over the three consecutive years, were very similar. The highest overlap (99.7 %) was observed in one center over two consecutive years. The overlapping areas were very high (93.6-95.7%) in 8 out of 9 inter-comparisons.

Conclusion: Despite the limitations of this study the yearly distribution of the HbA₂ measured in various centers appears a reliable tool to test HbA₂ standardization over different centers using different analytical methods.

Keywords: Harmonization; Hemoglobin A(2); Reference intervals; Standardization; β-thalassemia.