Effective screening for double heterozygosity of Hb E/α0-thalassemia

Abstract

One hundred and forty-one blood samples of hemoglobin E (Hb E) carriers were collected to define suitable cutoff values of Hb E level, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) as screening indicators for detecting individuals with double heterozygosity for Hb E/alpha(o)-thalassemia. Based on the values that gave 100% sensitivity, Hb E < 26%, MCV < 74 fl, and MCH < 24 pg were selected. Further validation of these selected values in additional 152 heterozygous Hb E pregnant women revealed 100% sensitivity, 86.2% specificity, and a 25.9% positive predictive value (PPV) for using Hb E cutoff point only, meanwhile, 100% sensitivity, 83.4% specificity, and 22.6% PPV were achieved for the MCV cutoff point. In addition, 100% sensitivity, 86.3% specificity, and 25.9% PPV were gained for the MCH cutoff point. Combining Hb E level with either MCV or MCH cutoff points, the specificity and PPV were increased to 95.1% and 50.0%, respectively. It is concluded that Hb E level < 26%, MCV < 74 fl, and MCH < 24 pg could be used for screening alpha(o)-thalassemia in heterozygous Hb E. However, to improve specificity and PPV of the tests, a combination of Hb E level < 26% with either MCV < 74 fl or MCH < 24 pg is recommended.

Hb A2/E Levels Found in Co-Inheritance with the α-Thalassemia-1 – –SEA/ Type Deletion and Either Hb E or β-Thalassemia

“…At a Hb E cut-off value of 21.54% (mean þ SD), 95.0% of --SEA /β E trait show Hb E at lower than the cut-off value, while 94.0% of Hb E trait had Hb E levels higher than the cut-off value. These results were consistent with the previous study that showed Hb E level is the best indicator for screening of α-thal-1 in Hb E heterozygotes (15,16). However, coinheritance of the --SEA / deletion with β-thal trait or homozygous Hb E did not result in a marked reduction of Hb A 2 /E levels.…”

“…The limitation of our study is that the laboratory data for an iron study which is used for classification of microcytic anemia type was not available. Furthermore, mean corpuscular Hb (MCH) and red cell distribution width (RDW), which have been reported for limited information in classifying thalassemia and other microcytic anemias (16,19,20), were also not available. Consequently, we do not know whether MCH and RDW can be used as alternative screening tools for differentiation of the --SEA / deletion coinheritances from their counterparts.…”

“…Based on a microcolumn chromatography method, a Hb E level less than 25.0% has been used for screening the α-thal-1 --SEA type deletion in Hb E trait (15). Moreover, Hb E levels of <26.0% measured by HLPC and mean corpuscular volume (MCV) of <74 fL is the best indicator for screening of α-thal-1 (--SEA and --THAI deletions) (16). There is no report of Hb A 2 /E levels in heterozygous α-thal-1 --SEA / type deletion coinherited with β-thal trait or homozygous Hb E. The aim of this study was to compare hemoglobin (Hb), MCV and Hb A 2 /E levels in the --SEA / deletion co-inherited with β-thal trait, Hb E trait or homozygous Hb E with β-thal trait, Hb E trait or homozygous Hb E, respectively.…”

Co‐inheritance of α0‐thalassemia elevates Hb A2 level in homozygous Hb E: Diagnostic implications

“…1 Similar prevalence has been reported in Lao PDR and Cambodia. 8,9 This however cannot be applied to a homozygous Hb E as Hb analysis shows no Hb A for comparison. Among these are Hb E-related disorders.…”

“…This has led to the generation of useful cutoff level of 25% Hb E when analyzed using Hb-HPLC analyzer for effective screening of a double heterozygous for Hb E/α 0 -thalassemia. 8,9 This however cannot be applied to a homozygous Hb E as Hb analysis shows no Hb A for comparison. 10 In routine thalassemia screening, all cases of this Hb EE syndrome are therefore subjected to further analysis of α-thalassemia by DNA testing.…”