Should sex differences be considered when applying mathematical indices and formulas for discriminating β- thalassemia minor from iron deficiency?

Background: β-thalassemia minor (BTM) and iron deficiency (ID) are common disorders characterized by microcytosis and/or hypochromasia, leading to a challenge in their discrimination during mass-screening programs especially in developing countries where resources are limited. It has been shown with varying reliability that quick exclusion of either disorder could be achieved mathematically using RBC-based indices and formulas. However, none of these proposed indices and formulas considered the sex-based hematological differences. This comparative retrospective study examined the efficacy of using sex-based RBC indices in the mathematical discrimination BTM and ID in adult males and females. Methods: The CBC of randomly selected eight hundred adults diagnosed with BTM or ID (200M & 200F BTM, and 200M & 200F ID) were used in the comparisons. The discrimination power, in terms of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and Youden index were calculated for all subjects and separately for males and females for 20 mathematical indices and formulas. Results: Data revealed significant differences in the RBC-based indices between males and females for both BTM and ID groups. Significant variation in reliability indicators for the different indices and formulas were discovered between males and females samples. Conclusion: Sex-based indices and formulas are necessary to improve the reliability in mathematically discriminating between BTM and ID in mass screening programs. We also advocate for a large–scale multicenter study to establish the parameters of such indices and formulas with sex and age. Keywords: β-thalassemia minor, Iron deficiency, Mathematical indices and formulas, Discrimination power, Sensitivity, Specificit