Hereditary spherocytosis diagnosed with extremely low glycated hemoglobin compared to plasma glucose levels.

Glycated hemoglobin (HbA1c) is an important indicator of glycemic control in patients with diabetes. High-performance liquid chromatography (HPLC) is the most commonly used method for measuring HbA1c levels; as HPLC measures all hemoglobin types, the values can be influenced by hemoglobin variants. Moreover, as HPLC-HbA1c levels are low in some diseases, including hemolytic anemia, it may be difficult to differentiate hemoglobin variants from these diseases based on HPLC-HbA1c levels alone. Similar HbA1c values using both HPLC and immunoassays (IAs) are noted for these diseases, while discrepancies are noted in the case of hemoglobin variants. Herein, we describe our process of differential diagnosis for hereditary spherocytosis, the most common inherited hemolytic anemia, in a 56-year-old man presenting with a low HPLC-HbA1c level compared to the glucose concentration, concomitant with anemia, jaundice, hyperbilirubinemia, cholelithiasis, and splenomegaly. There was a discrepancy between HbA1c levels measured with HPLC and IAs and glycated albumin levels. The possibility of hemoglobin variants was unlikely, based on the chromatography and isoelectric focusing results. The haptoglobin levels and reticulocyte counts were low and high, respectively. The direct and indirect Coomb's tests were negative. The presence of spherocytes on blood smears and flow cytometric analysis of the eosin-5-maleimide binding test supported a diagnosis of hereditary spherocytosis. We recommend that when a discrepancy between HPLC-HbA1c levels and glucose concentrations is noted, clinicians should consider hemolysis or hemoglobin variants as the diagnosis. It should be considered that a discrepancy between HbA1c levels measured with HPLC and IAs does not specifically exclude hemolysis. © The Japan Diabetes Society 2020.