EE score: an index for simple differentiation of homozygous hemoglobin E and hemoglobin E-β0-thalassemia

Kritsada Singha; Goonnapa Fucharoen; Kanokwan Sanchaisuriya; Supan Fucharoen

doi:10.1515/cclm-2018-0089

Article

EE score: an index for simple differentiation of homozygous hemoglobin E and hemoglobin E-β⁰-thalassemia

Kritsada Singha , Goonnapa Fucharoen , Kanokwan Sanchaisuriya and Supan Fucharoen

Published/Copyright: April 18, 2018

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 56 Issue 9

Abstract

Background:

The objective of the study was to describe a formula based on hemoglobin (Hb)A₂ and HbF levels for differentiation of homozygous HbE and HbE-β-thalassemia.

Methods:

A total of 1256 subjects suspected for homozygous HbE or HbE-β⁰-thalassemia were recruited at the ongoing thalassemia screening program at Khon Kaen University, Thailand. Hb analysis was done using capillary electrophoresis. Genotyping was based on DNA analysis. An arbitrary formula based on HbA₂ and HbF was developed statistically for differentiation of the two conditions. Validation was carried out prospectively on another 139 subjects encountered at routine laboratory.

Results:

Among 1256 subjects, Hb and DNA analyses identified cases with homozygous HbE (n=1076, 85.7%), HbE-β⁰-thalassemia (n=140, 11.1%), HbE-δβ⁰-thalassemia (n=30, 2.4%) and unknown HbE-related disorder (n=10, 0.8%). An inverse correlation between the amounts of HbA₂ and HbF in HbE-β⁰-thalassemia was observed. With differences in the amounts of HbA₂ and HbF between the groups, an arbitrary score (7.3 HbA₂+HbF) was developed where score above 60 indicated HbE-β⁰-thalassemia. Application of this score on another 139 subjects showed accurate prediction of HbE-β⁰-thalassemia with 100% sensitivity, 96.5% specificity, 85.7% positive predictive value and 100% negative predictive value. Successful application onto couples at risk was demonstrated.

Conclusions:

An established score should prove useful in the differentiation of homozygous HbE and HbE-β⁰-thalassemia in routine setting and lead to a significant reduction in number of referring cases for molecular testing.

Keywords: differential diagnosis; HbA2; HbF; HbE-β0-thalassemia; homozygous HbE

Author contributions: KS performed the experiment, analyzed the data and developed initial manuscript. GF helped to design the study, supervised the research, interpreted the data and wrote the manuscript. KaS helped in statistical analysis, research design and interpretation of the data. SF designed the experiment, facilitated the study, acquisition of research grant, analyzed the data, critically revising and approved the final manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was supported by a grant from Khon Kaen University, Thailand. KS is supported by the Post-Doctoral training program of the Graduate School of Khon Kaen University, Khon Kaen, Thailand (grant number 59256).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2018-01-24

Accepted: 2018-03-06

Published Online: 2018-04-18

Published in Print: 2018-08-28

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Articles in the same Issue

https://doi.org/10.1515/cclm-2018-0089

Keywords for this article

differential diagnosis; HbA2; HbF; HbE-β0-thalassemia; homozygous HbE