Evaluation of HbA1c determination methods in patients with hemoglobinopathies.

OBJECTIVE: To evaluate commercially available determination methods for HbA1c in patients with hemoglobin variants. RESEARCH DESIGN AND METHODS: HbA1c values were determined with various commercially available methods, including ion-exchange high-performance liquid chromatography (HPLC), boronate affinity assay, and immunoagglutination in patients with the hemoglobin mutations Hb Graz, Hb Sherwood Forest, Hb O Padova, Hb D, and Hb S. RESULTS: The effect of hemoglobinopathies on glycohemoglobin measurements was highly method dependent. The HPLC methods for HbA1c determination lacked the resolution necessary to differentiate hemoglobin variants. They demonstrated additional peaks in the chromatograms and HbA1c results either too low or too high compared with the nondiabetic reference range. With all immunoassays, Hb Graz demonstrated falsely low values. The other hemoglobinopathies in our study caused falsely low and/or high HbA1c results in immunoagglutination methods. The boronate affinity method showed values in an acceptable range for all hemoglobin variants. CONCLUSIONS: Because of the local occurrence of Hb variants and the ethnic origin of a given population, every individual laboratory must establish and validate its own assay method. In managing diabetic patients, knowledge of hemoglobinopathies influencing HbA1c determination methods is essential because hemoglobin variants could cause mismanagement of diabetes resulting from false HbA1c determinations.