Background: Hemoglobin A1c (HbA1c) acts as the primary biomarker for evaluating long-term glucose regulation. Nevertheless, high concentrations of fetal hemoglobin (HbF) can affect the accuracy of HbA1c assays in a manner dependent on the method used, possibly leading to falsely low HbA1c readings even when there is considerable hyperglycemia.
Case Presentation: The outpatients showed significant hyperglycemia (random blood glucose: 433 mg/dL) and highly positive urine ketones (+++), aligning with a diagnosis of diabetic ketoacidosis. Ironically, HbA1c obtained through standard immunoassay was 6.5%, which is categorized within the non-diabetic range. Follow-up hemoglobin fractionation showed an increased fetal hemoglobin (HbF) concentration of 4.1%, causing worry about assay interference and leading to a reassessment of the HbA1c outcome.
Conclusion: Elevated fetal hemoglobin (>4%) can falsely lower HbA1c, especially with immunoassay or boronate-affinity methods. Ion-exchange HPLC or electrophoresis is recommended, and clinicians should integrate alternative glycemic markers or continuous glucose monitoring to guide management accurately.
hemoglobin A1c, fetal hemoglobin, HbF interference, Ion-exchange HPLC, capillary electrophoresis, glycemic markers
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