Effects of Hemoglobin C and S Traits on the Results of 14 Commercial Glycated Hemoglobin Assays

Abstract

Glycated hemoglobin is widely used in the management of diabetes mellitus. At least 300,000 Americans with diabetes mellitus have the hemoglobin (Hb) C or S trait. The accuracy of HbA1c methods can be adversely affected by the presence of these traits. We evaluated the effects of HbC and HbS traits on the results of 14 commercial HbA1c methods that use boronate affinity, enzymatic, immunoassay, and ion exchange methods. Whole blood samples from people homozygous for HbA or heterozygous for HbC or HbS were analyzed for HbA1c. Results for each sample type were compared with those from the CLC 330 comparative method (Primus Diagnostics, Kansas City, MO). After correcting for calibration bias by comparing results from the homozygous HbA group, method bias attributable to the presence of HbC or HbS trait was evaluated with a clinically significant difference being more than 10% (ie, 0.6% at 6% HbA1c). One immunoassay method exhibited clinically significant differences owing to the presence of HbC and HbS traits.

Effects of hemoglobin S variants on the measurement of glycosylated hemoglobin A1c by four analytical methods

“…This finding confirms that whenever we use an immunoassay to measure HbA1c, there is a probability that patients with the HbS trait will be undertreated due to the lower HbA1c results produced, as the immunoassay would be unable to identify the presence of hemoglobin variants. However, in a study by Mongia SK et al, common Hb traits, such as HbAS and HbAC, did not interfere with the Bio-Rad Variant II Turbo CE-HPLC HbA1c NA not available assay used in this study [27]. In contrast with the above studies, we found no significant differences in the HbA1c results for our SCT patients from either HPLC or immunoassays.…”

Effects of Hemoglobin Variants on Hemoglobin A1c Values Measured Using a High-Performance Liquid Chromatography Method

“…In a series of publications between 2000 and 2008, it was noted that HbS does not interfere with HPLC method 1 and immunoturbidimetric methods, [22][23][24] an observation that this study has confirmed.…”

Current controversies in the use of haemoglobin A1c

“…An international consensus committee has recommended that results should be reported worldwide in both SI units (mmol ⁄ mol) and derived NGSP ⁄ DCCT units (%) [38]. Acknowledging the limitations of the ADAG study, the consensus committee decided against the routine HbC [92] HbE [93] HbD [93] Hereditary persistence of HbF [94] Chemical derivatives of haemoglobin Carbamylated haemoglobin (e.g. as a result of uraemia) [95] Acetylated haemoglobin (e.g.…”