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Hemoglobin A1c (HbA1c) measurement can be affected by hemoglobin variants through altered erythrocyte survival and method-specific analytical interference. This study assessed the influence of hemoglobin variants on HbA1c measurement by high-performance liquid chromatography (HPLC) in patients with hemoglobinopathy at Treichville University Hospital. This cross-sectional analytical study included 150 participants: 50 controls and 100 patients with confirmed hemoglobinopathy. Hemoglobin phenotypes were determined by electrophoresis. Blood glucose, complete blood count parameters, and the HPLC fractions HbA1c, HbA1a, HbA1b, and LA1C+ were measured. Group comparisons used the Mann-Whitney test, and phenotype comparisons used the Kruskal-Wallis test. The hemoglobinopathy group comprised SS (62%), SC (27%), AS (6%), an SFA2 electrophoretic profile (3%), and CC (2%). Mean blood glucose did not differ significantly between controls and participants with hemoglobinopathy (0.87 ± 0.13 g/L vs. 0.85 ± 0.07 g/L; p = 0.321). In contrast, mean HbA1c was markedly lower in the hemoglobinopathy group (1.29 ± 0.50% vs. 5.64 ± 0.54%; p < 0.001). Patients also had lower hemoglobin concentrations (8.75 ± 1.88 g/dL vs. 14.53 ± 1.58 g/dL; p < 0.001), indicating substantial anemia. HbA1c differed across electrophoretic categories (p = 0.0030), with the lowest values observed in CC and SFA2. LA1C+ also varied significantly by phenotype (p = 0.00011). Hemoglobin variants substantially affect HPLC HbA1c measurement and interpretation, producing a marked discordance between glycemia and HbA1c. In patients with hemoglobin variants, especially SS, SC, CC, or an SFA2 electrophoretic profile, HbA1c should not be interpreted in isolation and should be assessed alongside the chromatogram, blood glucose, hematological indices, and hemoglobin phenotype. Alternative glycemic markers may be required when HbA1c is unreliable.
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Gervais et al. (2026) studied this question.
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