Abstract Β-thalassemia trait (β-TT) is a common hemoglobin disorder that is frequently confused with iron deficiency anemia (IDA), leading potentially low-yield confirmatory hemoglobin fraction analysis and increased use of healthcare resources. To assess the appropriateness of β-TT screening in patients with microcytic hypochromic anemia and to detect laboratory and clinical predictors of potentially low yield testing. A total of 12,622 patients with microcytic hypochromic anemia who underwent hemoglobin fraction analysis by HPLC between February 2023 to July 2025 were included in this retrospective cross-sectional study. Data on complete blood counts, Pathologist remarks, and HPLC results were collected. Red cell indices (Mentzer Index) , HbA₂ levels, and recorded clinical context were used to operationally classify testing appropriateness. Multivariable multinomial logistic regression was used to identify predictors of test appropriateness. Among the 12,622 patients, 3932 (31.2%) had confirmed β-TT, 8312 (65.9%) had non-β-TT microcytic anemia, and 378 (3.0%) had borderline HbA₂ values. Testing was categorized as appropriate in 2544 cases (20.2%), potentially low-yield in 5678 cases (45.0%), and unclear in 4400 cases (34.9%) based on red cell indices, HbA 2 levels, and clinical context. While suspected β-TT significantly predicted appropriate testing, suspected IDA (OR 4.00, p < 0.001), female sex (OR 1.50, p < 0.001), and post-transfusion samples (OR 4.27, p < 0.001) were independently associated with potentially low-yield testing. The possible masking effect of iron deficiency on β-TT detection was reflected by the fact that 490 patients (3.9%) were recommended to undergo a repeat HPLC after iron supplementation to rule out iron deficiency-mediated suppression of HbA₂ as a potential masking factor for β-TT. A significant portion of β-TT screening my be potentially low-yield, which may affect clinical results and available resources. Test utilization may be optimized and diagnostic accuracy may be improved by evaluating iron status, repeating testing after iron correction when indicated and interpreting red cell indices in appropriate clinical setting.
Abideen et al. (Sun,) studied this question.