Comprehensive screening for coexisting heterozygous α-thalassemia in hemoglobin E trait.

A sensitive screening for the coexistence of α-thalassemia and the hemoglobin E (Hb E) trait is important to identify at-risk couples for hydrops fetalis. However, previous cutoff values have shown a positive predictive value (PPV) of only 50% or less. This study aimed to define more specific indicators to reduce the need for DNA tests. Patients with Hb E trait, as diagnosed by high performance liquid chromatography (HPLC) and/or isoelectric focusing (IEF) techniques, were tested for α-thalassemia and α-thalassemia deletions using multiplex gap polymerase chain reaction. Iron deficiency anemia (IDA) were excluded using a red cell distribution width (RDW) of more than 14.5%. From 390 specimens, suitable cutoff values showing a 100% sensitivity for detection of heterozygous α-thalassemia were an Hb E level of less than 22% by HPLC, a mean corpuscular volume (MCV) of less than 72 fL, and a mean corpuscular hemoglobin (MCH) level of less than 22.5 pg. Comparable results were obtained in the validation cohort ( = 179). Using a combination of Hb E with either MCV or MCH cutoff points gave a PPV of 76.2% and 77.4%, respectively. IDA was reported to interfere with Hb E level. In this study, we excluded IDA using RDW of more than 14.5% to enhance the test specificity. Lower cutoff screening values can be used to exclude α-thalassemia in the Hb E trait yielding a higher specificity in a normal RDW condition. This can save the cost and labor of DNA testing.