Prediction the Occurrence of Thalassemia With Hematological Phenotype by Diagnosis of Abnormal HbA1c.

Abstract

Background: The current investigation aims to analyze the occurrence of thalassemia in patients who participated in hemoglobin A1c (HbA1c) testing in clinical laboratory showing high hemoglobin F (HbF) level (≥ 1.5%) or abnormal Hb peak and predict the main influence factors by using different statistical models.

Methods: The current investigation is a single-center retrospective cohort study. HbA1c concentration was detected by using TOSOH HLC-723G8 glycated hemoglobin analyzer. SNaPshot SNP (Single Nucleotide Polymorphism) typing and AccuCopy technology were employed to detect mutations in thalassemia-related pathogenic genes.

Results: A total of 126 patients endured high HbF levels or abnormal Hb peak during HbA1c detection, and 66.7% of subjects (n = 84) showed thalassemia mutations. Three heterozygosity mutations, including c.52A>T (p.K18*), c.-78A>G, and c.126_129delCTTT(p.F42Lfs*19) present in HBB gene, were also identified. --^SEA/αα mutation demonstrated the youngest ages (p < 0.001). 17 M (p < 0.001) and 41/42 M (p < 0.01) mutations with β-thalassemia showed higher HbF levels compared with patients without thalassemia mutations. Except for -α^3.7, mutations in thalassemia showed lower levels of mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) compared with patients without thalassemia mutations. Patients with thalassemia mutations showed younger age (p < 0.001), lower Hb (p < 0.001), MCV and MCH levels (p < 0.001), higher red blood cell (RBC) count (p < 0.001), and platelet distribution width (PDW) level (p = 0.007) than patients without thalassemia mutations. Three statistical models indicate MCV is the most valuable independent factor for predicting thalassemia and ROC (receiver operating characteristic) curves analysis of AUC (Area Under the Curve) of 0.855 (95% CI [0.787-0.923], p < 0.001) with MCV.

Conclusion: High HbF level (≥ 1.5%) or abnormal Hb peak present in HbA1c testing indicated high incident rate of thalassemia. MCV is the most valuable independent predicting factor for subjects having thalassemia.