RESUMO
INTRODUCTION: Detection of ß-thalassemia trait or carriers (ß-TT) depends significantly on an increase in Hemoglobin A2 (HbA2) levels, which is found at low levels (<3%) in normal healthy individuals and elevated levels (≥3.5%) in ß-TT individuals. The study was designed to evaluate the reliability of the diagnostic parameter HbA2 in the differentiation of ß-TT and non-ß-TT in Saudis. METHODS: The widely used high performance liquid chromatography (Variant II Bio-Rad) was used to measure HbA2 levels in blood. Sanger sequencing was used to screen the variation in globin genes (HBB, HBD, HBA1, and HBA2). All the study subjects were divided into ßTT and non-ßTT (wild) categories based on the presence or absence of HBB variations and further sub-divided into false positive, true positive, false negative, and true negative, based on HbA2 values. RESULTS: Out of 288 samples, 96 had HBB gene mutations. Of the 96 ß-TT samples, sickle cell trait (SCT) samples (n = 58) were excluded, while the remaining (38 ß-TT) were included in the detailed analysis: seven subjects with the HBB mutation had normal HbA2 (<3%), and three were borderline (3.1-3.9%). The remainder (n = 28) had an elevated HbA2 level (>4%). Based on HbA2 analysis alone, both these groups would be incorrectly diagnosed as normal. Similarly, of the 189 non-ß-TT samples, 179 had normal HbA2, eight had borderline HbA2, and two had a HbA2 level above 4%. Based on HbA2 analysis alone, borderline and >4% HbA2 individuals, negative for ß-TT, can be incorrectly diagnosed as carriers. CONCLUSION: Given the percentage of samples falling in the HbA2 "borderline" and "normal" categories, it can be concluded that HbA2 has a measure of unreliability in the diagnosis of ß-thalassemia carriers.