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Introduction: Few data are available on the alignment of the different methods used for HbA2 quantitation and recent external quality survey results show a consistent spread of HbA2 values. To this aim, a comparison study among the actual best performing techniques for HbA2 determination, comprising HPLC and CE methods, was performed. Methods: A total of 80 blood samples collected from normal subjects and β-thalassemia carriers were analyzed by different HPLC (Bio-Rad Variant I, Bio-Rad Variant II, Menarini HA-8160, Tosoh G7, Tosoh G8) and capillary electrophoresis (Beckman Coulter MDQ and ProteomeLab PA 800, Sebia Capillarys 2) methods. Patient's samples with clinically relevant hemoglobin variants (HbC, HbD, HbE, HbS, and δ-chain variants) were also tested by all methods. Results: The mean within-run imprecision of HbA2 measurement (expressed as CV, %) was between 0.5% and 4.4% (HPLC) and between 1.2% and 4.4% (capillary electrophoresis). The comparison study showed that the different methods were highly correlated ( r between 0.974 and 0.997) although biased each other. HbA2 determination in presence of abnormal hemoglobins was variously interfered by both HPLC and CE methods. Concerning HbF, the mean imprecision at HbF values ≥1.5% was between 1.2% and 8.2% (as CVs). Conclusions: A poor alignment of routine methods for HbA2 measurement was found. The need of a better standardization of HbA2 measurement procedures was underlined. [ABSTRACT FROM AUTHOR]

Introduction: Few data are available on the alignment of the different methods used for HbA2 quantitation and recent external quality survey results show a consistent spread of HbA2 values. To this aim, a comparison study among the actual best performing techniques for HbA2 determination, comprising HPLC and CE methods, was performed. Methods: A total of 80 blood samples collected from normal subjects and β-thalassemia carriers were analyzed by different HPLC (Bio-Rad Variant I, Bio-Rad Variant II, Menarini HA-8160, Tosoh G7, Tosoh G8) and capillary electrophoresis (Beckman Coulter MDQ and ProteomeLab PA 800, Sebia Capillarys 2) methods. Patient's samples with clinically relevant hemoglobin variants (HbC, HbD, HbE, HbS, and δ-chain variants) were also tested by all methods. Results: The mean within-run imprecision of HbA2 measurement (expressed as CV, %) was between 0.5% and 4.4% (HPLC) and between 1.2% and 4.4% (capillary electrophoresis). The comparison study showed that the different methods were highly correlated ( r between 0.974 and 0.997) although biased each other. HbA2 determination in presence of abnormal hemoglobins was variously interfered by both HPLC and CE methods. Concerning HbF, the mean imprecision at HbF values ≥1.5% was between 1.2% and 8.2% (as CVs). Conclusions: A poor alignment of routine methods for HbA2 measurement was found. The need of a better standardization of HbA2 measurement procedures was underlined. [ABSTRACT FROM AUTHOR]

The increase in haemoglobin (Hb)A2 level is the most significant parameter in the identification of β thalassaemia carriers. However, in some cases the level of HbA2 is not typically elevated and some difficulties may arise in making the diagnosis. For these reasons the quantification of HbA2 has to be performed with great accuracy and the results must be interpreted together with other haematological and biochemical evidence. The present document includes comments on the need for accuracy and standardisation, and on the interpretation of the HbA2 value, reviewing the most crucial aspects related to this test. A practical flow-chart is presented to summarise the significance of HbA2 estimation in different thalassaemia syndromes and related haemoglobinopathies. [ABSTRACT FROM AUTHOR]

The establishment of reference systems for the standardization of hemoglobin A 2 (HbA 2 ) and fetal hemoglobin (HbF), both critical for improving diagnostic accuracy in conditions such as β-thalassemia and sickle cell disease, are described. Efforts were led by the IFCC and other groups to address and reduce the variability in laboratory measurements of these hemoglobins. This document outlines the production of certified reference materials (CRMs) for HbA 2 and the development of a reference measurement procedure using isotope dilution mass spectrometry. Similarly, standardizing HbF is essential for supporting diagnostic and therapeutic strategies, particularly in managing sickle cell disease. HbF levels can predict disease outcomes and guide treatment plans. Significant challenges remain in achieving consistent measurement across laboratories, and the process for standardization for this minor hemoglobin has just begun. We are confident that the implementation of these reference systems will provide improved accuracy and traceability in the future., Competing Interests: Declaration of competing interest A. Mosca and R.P. are components of the University of Milano, carrying out researches on clinical studies, methods development and validation for diabetes and hemoglobin related disorders, sometimes sponsored by various Companies. Both have received speakers’ honoraria or consulting fees from Menarini Diagnostics, Sebia, and Tosoh Bioscience., (Copyright © 2024. Published by Elsevier B.V.)

Drepanocytosis is a genetic disease relevant for its epidemiological, clinical and socio-economic aspects. In our country the prevalence is highly uneven with peaks in former malaria areas, but migration flows in recent years have led to significant changes. In this document we review the screening programs currently existing in Italy with particular emphasis on newborn screening, which in other countries around the world, including within Europe, is at most universal and mandatory. The essential laboratory issues are reviewed, from sampling aspects (cord blood or peripheral), to the analytical (analytical methods dedicated to neonatal screening and adult carrier detection) and post analytical (reporting, informative) ones. An economic analysis based on data collected in the province of Modena is also proposed, clearly showing that neonatal screening is also beneficial from an economic point of view., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background and Aims: The monitoring of yearly distributions of HbA 2 measured has been indicated as a reliable indicator of worldwide standardization., Materials and Methods: Measurements/year of HbA 2 have been collected over three consecutive years in 15 Italian laboratories each using the same analytical method over three years period. HbA 2 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 HbA 2 measured in various centers appears a reliable tool to test HbA 2 standardization over different centers using different analytical methods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Diabetes-driven retinal neurodegeneration has recently been shown to be involved in the initial phases of diabetic retinopathy, raising the possibility of setting up a preventive strategy based on early retinal neuroprotection. To make this possible, it is crucial to identify a biomarker for early retinal neurodegeneration. To this end, in this study, we verified and confirmed that, in the Akita mouse model of diabetes, the thinning of the retinal nerve fiber layer/ganglion cell layer (the RNFL/GCL-the layer that contains the retinal ganglion cells) precedes the death of these same cells, suggesting that this dysfunction is a possible biomarker of retinal neurodegeneration. We then confirmed the validity of this assumption by starting a neuroprotective treatment (based on nerve growth factor eye drops) in concert with the first demonstration of RNFL/GCL thinning. In this way, it was possible not only to avoid the loss of retinal ganglion cells but also to prevent the subsequent development of the microvascular stage of diabetic retinopathy. In conclusion, in the case of diabetes, the thinning of the RNFL/GCL appears to be both a valid biomarker and a pharmacological target of diabetic retinopathy; it precedes the development of vascular dysfunctions and represents the ideal starting point for prevention.

Background and Aims: Glycated albumin (GA) may assess glycometabolic control over a short period of time respect to HbA 1c , and its use to screen for gestational diabetes in pregnancy has been suggested. To this regard few data on reference intervals (RI) for GA on Europid women have been collected, only from cross-sectional investigations. Aim of this work has been to collect trimester-specific RI for GA in physiological pregnancies, following a longitudinal prospective study., Methods: Forty-five healthy pregnant Europid women have been enrolled for whom a GDM screening test was scheduled at 24-28 weeks, in 5 different Italian centers. Only those negative to the OGTT were included. The women had 4 successive visits at 6-10 weeks of gestation, at 16-18 weeks, at 24-28 weeks and at the end of pregnancy. ALT, AST, total bilirubin, C-reactive protein, cholinesterase, creatinine, GGT, glycated albumin, iron, total serum proteins, transferrin were measured in duplicate on aliquots of serum samples by a central laboratory., Results: The RI (2.5-97.5 percentiles) for GA were 11.1-14.8 % (I visit), 10.9-15.6 % (II visit), 10.6-14.1 % (III visit) and 10.7-14.3 % (IV visit). The RI of other biomarkers confirmed previously published data. The RI for serum cholinesterase we present are novel, and were 5049-9906 U/L (Iv), 4212-8965 U/L (IIv), 3518-8470 U/L (IIIv) and 3945-8727 U/L (IVv)., Conclusions: Trimester-specific RI are important for using GA and serum cholinesterase in pregnancy. However, considering the high inter-individual variability of both markers, the use of longitudinal interpretations of the individual variations of both proteins during pregnancy should be preferred., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The decline of the estimated glomerular filtration rate (eGFR) and the presence of albuminuria are the typical hallmarks of kidney disease arising as one of the most frequent diabetic complications over a long period of time, generally known as diabetic nephropathy or diabetes kidney disease (DKD). However, a decline in the renal function may occur in diabetic patients for other reasons unrelated to glycemic control, and this condition is known as non-diabetic kidney disease (NDKD). In this opinion paper we will review these conditions, and we outline the importance of other investigations, such as kidney biopsy and the measurement of novel biomarkers, in order to identify the disease progression early, and to allow a timely intervention. We will also focus on the actual limits of the quantitative measurements of albumin in urine, especially with regards to potential interferences due to the treatment of patients with statins., (Copyright © 2021 Elsevier B.V. All rights reserved.)