Population-adjusted cut-off: A new approach for enhancing the diagnostic efficacy of hematological discrimination formulae for screening β-Thalassemia trait

Screening for β-thalassemia trait (βTT) is crucial for preventing β-thalassemia major in offspring. Although hematological discrimination formulae (HDF), developed using complete blood count parameters, are cost-effective tools for screening βTT, their performance varies across different populations. This study evaluated the performance of 32 HDF for screening βTT in the Sri Lankan population. Data were retrieved from laboratory databases and categorized into confirmed βTT and non-βTT groups based on high-performance liquid chromatography results. The βTT screening performance of the HDF was assessed using accuracy measurements, the receiver operating characteristic (ROC) curve, and Youden’s index (YI). Furthermore, a population-adjusted cut-off was determined using the Index of Union (IU) method to optimize the predictive accuracy of HDF in screening βTT. Bordbar demonstrated excellent predictive performance in males (AUC = 0.908; YI = 0.815), while Shine & Lal, Kerman-I, Nishad, Sehgal, Bordbar, and Roth demonstrated high discriminative ability in females (AUC > 0.833; YI > 0.666). Applying a population-adjusted cut-off improved the βTT screening potential of Shine & Lal, Kerman-I, Nishad, Bordbar, and Roth in males (AUC > 0.911; YI > 0.822) and enhanced the performance of Kerman-II in females (AUC > 0.861; YI > 0.722). Notably, Shine & Lal (AUC = 0.937; YI > 0.873) and Nishad (AUC = 0.897; YI > 0.794) demonstrated the best performance for males and females, respectively, when a population-adjusted cut-off was applied for screening βTT. In conclusion, determining a population-adjusted cut-off is a new initiative to enhance the βTT screening performance of HDF across different populations.