(359) Hemoglobinopathy screening in the era of expanded carrier screening: is hemoglobin electrophoresis necessary?

ACOG recommendations for hemoglobinopathy screening involve complete blood count with MCV, with hemoglobin electrophoresis recommended for high-risk populations. Expanded carrier screening (ECS) involves testing for mutations associated with hemoglobinopathy. Our objective was to compare detection rates of hemoglobinopathy carriers through the use of  electrophoresis versus expanded carrier screening (ECS).

Study Design:

This is a retrospective cohort study. Participants include patients who underwent concomitant hemoglobin electrophoresis and ECS during their initial prenatal care visit in 2022. In our multiethnic population, electrophoresis is routine. Demographics, electrophoresis, ECS results and MCV were recorded, with microcytosis defined as MCV< 80fL. Those with a known clinical diagnosis of a hemoglobinopathy were excluded. Fisher’s exact test was used for statistical comparison.

Results:

506 patients were included. Table 1 describes the sensitivity of screening based on testing strategy. There were 129 hemoglobinopathy carriers (25.5%), including 33 with beta-chain abnormalities, 86 alpha-thalassemia carriers, and 10 who were carriers for both. ECS identified all 129 carriers, while electrophoresis detected abnormal globin chains in 43 carriers (33.5%). Electrophoresis also identified 6 patients with globin chain variants of no clinical significance. Of 96 alpha-thalassemia carriers detected by ECS, 87 were “silent carriers” (aa/a-), and 9 had deletion of two coding genes. Microcytosis was present in all 9 patients with the two-gene deletion. While microcytosis was more common in “silent carriers” (23.0% vs 6.6%; p< .001), most “silent carriers” were normocytic.

Conclusion:

There was no incremental benefit to hemoglobin electrophoresis in those undergoing ECS. In addition, ECS detects silent alpha thalassemia carriers, most of whom are normocytic. While we did not identify a clinical benefit in identifying “silent carriers”, in those at highest risk of severe forms of alpha-thalassemia (including Hemoglobin H disease) ECS is superior to conventional screening with electrophoresis and MCV.