Additional value of red blood cell parameters in predicting uncommon α-thalassemia; experience from 10 years of α-globin gene sequencing and copy number variation analysis.

Abstract

The diagnosis of rare forms of α-thalassemia requires laborious genetic analyses. Accurate sample selection for such evaluation is therefore essential. The main objectives of this study were to investigate the predictive power of red blood cell parameters to detect rare forms of α-thalassemia (substudy 1), and to explore the frequency of rare versus common forms of α-thalassemia in our sample population (substudy 2). In substudy 1, we reviewed all blood samples selected for extended α-hemoglobinopathy evaluation at our laboratory during 2011-2020 (n= 1217), which included DNA sequencing and/or copy number variation analysis. We assessed α-thalassemia positive samples at different levels of mean corpuscular hemoglobin (MCH) alone and in combination with results for red blood cell count (RBC) or red cell distribution width (RDW). In substudy 2, we examined the distribution of α-thalassemia genotypes for all samples submitted to a first-tier hemoglobinopathy evaluation at our laboratory during 2014-2020 (n= 6495). In substudy 1, both RBC and RDW added predictive value in detecting rare forms of α-thalassemia in samples from adults and children. In adult samples with MCH ≤ 23 pg, the presence of erythrocytosis increased the detection rate from 27% to 74% as compared to non-erythrocytosis, while normal RDW increased the detection rate from 36% to 86% as compared to elevated RDW. In substudy 2, rare forms of α-thalassemia were detected in 12% of α-thalassemia positive samples. Initial assessment of MCH, RBC, and RDW provided valuable predictive information about the presence of rare forms of α-thalassemia during hemoglobinopathy evaluation.