Prenatal Hemoglobinopathy Evaluation David M. Manthei,* Shih-Hon Li, David F. Keren, and Carmen Gherasim CASE DESCRIPTION A 22-year-old female at 11 weeks gestation with a family history of sickle cell trait (SCT) underwent hemoglobinopa- thy screening. High-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) evaluations are displayed (Fig. 1). Red blood cell (RBC) indices include: hemoglobin (Hb) 11.5 g/dL, reference interval (RI) 12–16 g/dL; mean corpuscular volume 79.0 fL, RI 79.0–99.0 fL; and RBC count 4.19 million/mL, RI 3.9–5 million/mL. She had no history of transfusions. Serum iron studies were not performed. QUESTIONS What is the likely diagnosis? How does one explain the differences in peaks between HPLC and CE? What are causes of decreased HbA2? The answers are below. A B Percentage (%) Fig. 1. Hemoglobin fractionation tracings by (A), HPLC (Bio-Rad Variant II) and (B), CE (Sebia Capillarys 2). HPLC fractions (A) included HbA2 of 2.3% (RI: 2.3–3.4%) and HbS of 38.9%. CE fractions (B) included HbA2 of 1.8% (RI 2.2–3.3%), HbS of 37.9%, and a Zone 1 peak of 1.5%. ANSWERS HbS is within 35–45%, indicating SCT (1). However, by HPLC, this HbS peak is irregular, and HbA2 should be high-normal or slightly increased due to inclusion of aged HbS (1). HbA2’ (a common benign delta-globin variant) elutes similarly to HbS by HPLC but distinctly in Zone 1 by CE; HbA2 will be artifactually decreased without inclusion of HbA2’ (2–4). Causes of truly low Department of Pathology, University of Michigan, MI *Address correspondence to this author at: Department of Pathology, at University of Michigan, 2800 Plymouth Rd., Building 36, Ann Arbor MI 48109. Fax 734-232-5360; e-mail dmanthei@med.umich.edu. Received February 8, 2021; accepted March 2, 2021 DOI: 10.1093/clinchem/hvab049 V C American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com. 1293 What Is Your Guess? Downloaded from https://academic.oup.com/clinchem/article/67/9/1293/6362128 by guest on 15 September 2022