Critical appraisal of the utility of 13 discriminant formulas for distinguishing beta thalassemia trait from iron deficiency in patients with microcytic anemia and the introduction of a new formula in a USA population

Abstract Iron deficiency anemia (IDA) and beta thalassemia trait (ß-TT) are two frequent causes of microcytic anemia that often pose a diagnostic dilemma with implications for management. Many discriminant formulas have been proposed for distinguishing these two conditions. However, there is a need for independent verifications of these formulas to determine their applicability to other populations, particularly more diverse populations, as seen in the United States. To date, no study has been performed in the United States to evaluate the utility of these formulas in distinguishing both conditions. The study objective was to evaluate the utility and predictive values of 13 discriminant indices and formulas for distinguishing ß-TT from IDA in a US population. We investigated 13 formulas comprising only hematologic parameters available on all analyzers. The investigational population consisted of 238 patients with microcytic anemia; 165 with a hemoglobin electrophoresis diagnosis of ß-TT and 73 diagnosed with IDA by clinician review or iron studies. The study population comprised 55% black or African American, 35% White, 5% Asian, 1.2% Native American, and 2.5% unidentified. Receiver operating characteristic curves were employed to evaluate the diagnostic performances of the formulas. All investigated formulas had poor sensitivities but high specificities. The three best-performing indices or formulas from those previously proposed for distinguishing ß-TT from IDA were the RBC (sensitivity 62.2%, specificity 87.1%), Green and King (MCV2×RDW/100 hemoglobin, Hb) with a sensitivity of 65.4% and specificity of 82.6%, and Wongprachum et al. (MCV×RDW/RBC) – 10 Hb) with a sensitivity of 63.6% and specificity of 82.6%. Areas under the curve (AUCs) were 0.68 for the RBC and, 0.67 for both Green and King and Wongprachum formulas. The Youden indices were 0.49, 0.48, and 0.46, respectively. The Mentzer index had a sensitivity of 63.4%, specificity of 81.7% and Youden index of 0.45. We introduced a new formula comprising the sum of three of the most readily obtained red cell parameters (RBC + Hb + MCV). It had a Youden index of 0.95, sensitivity of 96.8, specificity of 98.0, and AUC of 0.97, significantly outperforming other formulas in our study population (p=0.00). This is the first study in the USA evaluating the utility of multiple indices for distinguishing ß-TT from iron deficiency anemia. The best performing formulas in other studies did not perform well in our population. This necessitated an introduction of a new formula that demonstrates excellent potential to address the unique diversity of the US population.