Major Discordance in Hemoglobin A1c Measurement in Sickle Cell Trait: Effect of Analytical Methods

Hemoglobin A1c (HbA1c) is widely used for diagnosing and monitoring diabetes mellitus and reflects long-term glycemic control. However, hemoglobin variants may interfere with certain assay methods, leading to misleading results. We report the case of a 54-year-old woman with sickle cell trait and long-standing diabetes who presented with markedly discordant HbA1c values obtained using two different methods. High-performance liquid chromatography (HPLC) showed a significantly elevated HbA1c level, whereas a fluorescence immunoassay yielded a substantially lower value, despite persistently elevated fasting plasma glucose and normal hematologic parameters. Hemoglobin electrophoresis confirmed sickle cell trait. Fructosamine levels were consistent with recent hyperglycemia. This case highlights the potential for hemoglobin variants to interfere with specific HbA1c assay techniques, resulting in inaccurate assessment of glycemic control. Clinicians should interpret HbA1c results cautiously in patients with known or suspected hemoglobin variants and consider alternative markers, such as fructosamine, to guide diabetes management.