HbA2 Measurements in β-Thalassemia and in Other Conditions

Cornelis L Harteveld,Giovanni Ivaldi,Giuseppina Barberio,Piero Giordano

doi:10.4081/thal.2014.1832

Cornelis L Harteveld, Giovanni Ivaldi + Show 2 more

Open Access

https://doi.org/10.4081/thal.2014.1832

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Abstract

Quite a few papers have been written on the significance of elevated hemoglobin (Hb) A2 as a parameter for the diagnosis of β-thalassemia trait, on the cutoff values to be used in diagnostics and on the significance and effects of factors reducing or elevating the expression of HbA2 and last but not least on the need for reliable measurement methods and precise calibrations with accurate standards. However, little has been published on the causes that elevate or reduce the HbA2 levels in β- and a-thalassemia and in other conditions. For a better understanding of the value of a precise measurement of this parameter we summarize and elucidate in this review the direct and indirect mechanisms that cause the variations in HbA2 expression and that influence the value of this parameter in particular conditions. We conclude by explaining the advantages and disadvantages of trusting on a precise measurement in the complete diagnostic contest.

Highlights

In the carrier of b thalassemia one of the two b globin genes is either not or just barely expressed
Factors such as co-elutions, integration modes, calibrations, different columns, different buffers, different temperatures, different sample quality and concentrations have to be considered. These and other factors contribute to an inevitable variety of artifact that makes the use of normal cutoff intervals very risky when the HbA2 value alone is used to confirm or exclude a possible b-thalassemia trait
Dedicated devices are loading very small volumes of samples that may be fresh or not, may be homogeneous or partially sedimented or hypochromic [low mean corpuscular hemoglobin (MCH)] resulting in less genes will change from two b versus two d into Hb loaded and smaller HbA2 peaks and less preTo understand the significance of the expres- one b versus two d and from 97:3 to 48:3, cise integrations.[3]

Summary

Abstract tribute to the formation of the second embryonic

Quite a few papers have been written on the ly significance of elevated hemoglobin (Hb) A2 as a n parameter for the diagnosis of b-thalassemia o trait, on the cutoff values to be used in diagnostics and on the significance and effects of factors e reducing or elevating the expression of HbA2 and s last but not least on the need for reliable measurement methods and precise calibrations with u accurate standards. Little has been l published on the causes that elevate or reduce ia the HbA2 levels in b- and a-thalassemia and in other conditions. For a better understanding of rc the value of a precise measurement of this parameter we summarize and elucidate in this e review the direct and indirect mechanisms that m cause the variations in HbA2 expression and that influence the value of this parameter in particum lar conditions. Non Introduction hemoglobin Gower 2 (a2/e2), the fetal hemoglobin HbF (a2/g2), and both postnatal HbA2 (a2/d2) and HbA (a2/b2). While four a genes (two from the maternal and two from the paternal chromosome 16) are contributing to the formation of HbA and HbA2 only two b genes and two bd genes are providing the non-a counterpart to form these post-natal tetramers (Figure 1)

Loss of expression of one b gene

Measuring artifacts

More interfering factors

Coexisting iron deficiency

Findings

Device related artifacts