Interference of abnormal hemoglobins on the measurement of hemoglobin A1c by ion-exchange chromatography

Measuring Glycated Proteins: Clinical and Methodological Aspects

“…30,31 Coelution (or comigration) of HbF is a well known example of a variant hemoglobin causing error in the determination of N-modified hemoglobins by charge separation principles. [32][33][34][35][36][37] The comigration of hemoglobins S, C, and D, as well as their glycated derivatives, with HbA can produce an underestimation of the proportion of hemoglobin that is glycated, depending on the discriminatory power and level of sophistication of the chromatographic or electrophoretic apparatus. Hemoglobin variants carrying an additional negative charge may elute early, caus-COHEN AND CLEMENTS 60 ing false overestimation of the HbA1c value.…”

The number of unexpected HbA1c variants may be a greater problem in routine practice than is generally realized

“…Engback et al . concluded that any haemoglobin with a chromatographic mobility that differs from the norm interferes with the measurement of HbA 1c [32]. Accordingly, a very large number of patients with HbA 1c results (using non‐boronate methods) that are out of consensus with their blood glucose monitoring results may be due to abnormal haemoglobin variants.…”

Methodological discrepancies are not important

“…Any method comparisons involving significant imprecision on both axes should be compared with Deming's regression analysis and not linear regression. There is also no mention of the common confounder of glycated haemoglobin analysis, haemoglobin variants (especially haemoglobin S and fetal haemoglobin),5 and no mention of their incidence in the study population. The most interesting analysis that could have come from this study would have been a comparison of patients' glycated haemoglobin fractions with their own capillary glucose records over four months and regular plasma analyses in the laboratory, but unfortunately the relevant data were not presented.…”