Evaluation of HbA(1c) determination methods in patients with hemoglobinopathies

OBJECTIVE - To evaluate commercially available determination methods for Hb A(1c) in patients with hemoglobin variants. RESEARCH DESIGN AND METHODS - HbA(1c) values were determined with various c ommercially available methods, including ion-exchange high-performance liqu id 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 HbA(1c) determination lac ked the resolution necessary to differentiate hemoglobin variants. They dem onstrated additional peaks in the chromatograms and HbA(1c) results either too low or too high compared with the nondiabetic reference range. With all immunoassays, Hb Graz demonstrated falsely low values. The other hemoglobi nopathies in our study caused falsely low and/or high HbA(1c) results in im munoagglutination 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 a nd validate its own assay method. In managing diabetic patients, knowledge of hemoglobinopathies influencing HbA(1c) determination methods is essentia l because hemoglobin variants could cause mismanagement of diabetes resulti ng from false HbA(1c) determinations.