The Effect of Elevated Fetal Hemoglobin on Hemoglobin A_1cResults

Abstract

Hemoglobin A1c (HbA1c) is an important indicator of risk for complications in patients with diabetes mellitus. Elevated fetal hemoglobin (HbF) levels have been reported to interfere with results of some HbA1c methods, but it has generally been assumed that HbA1c results from boronate-affinity methods are not affected by elevated HbF levels. None of the previous studies used the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference method as the comparative HbA1c method. We, therefore, measured HbA1c in samples with normal and elevated HbF levels by several common assay methods and compared the results with those of the IFCC reference method.HbF levels of more than 20% artificially lowered HbA1c results from the Primus CLC 330/385 (Primus Diagnostics, Kansas City, MO), Siemens DCA2000 (Siemens Healthcare Diagnostics, Tarrytown, NY), and Tosoh 2.2+ (Tosoh Bioscience, South San Francisco, CA), but not the Bio-Rad Variant II (Bio-Rad Laboratories, Hercules, CA) and Tosoh G7. Physicians and laboratory professionals need to be aware of potential interference from elevated HbF levels that could affect HbA1c results, including those from boronate-affinity methods.

Three of 7 Hemoglobin A1c Point-of-Care Instruments Do Not Meet Generally Accepted Analytical Performance Criteria

“…The findings for Hb F interference found in this study were consistent with those from a previous study (23 ). The reason for the proportional interferences with the affinity methods is probably a result of the lower glycation rate for Hb F compared with Hb A and the lack of recognition of glycated Hb F by the Hb A 1c antibody with the immunoassay methods.…”

The Effect of Increased Fetal Hemoglobin on 7 Common Hb A1c Assay Methods

“…For the VII Turbo 2.0, although there was a statistically significant effect of HbF on HbA 1c results (VII Turbo 2.0 HbF ≤25%, P <0.0001), the differences were not clinically important. The current results for the Trinity Biotech HPLC support previous findings; the differences are both statistically significant ( P <0.0001) and clinically important for samples with increased HbF owing to lower glycation of HbF (1). However, for samples with HbF <15% the effect of HbF on HbA 1c results was not clinically important.…”

“…There are no manufacturer claims for HbF interference for this method. Moreover, as with immunoassay methods for which the same HbF interference applies (1), there is no indication in the reported result that an increased HbF level is present (unlike with ion-exchange HPLC); therefore, artificially low results will be reported for samples with HbF>15%. Physicians and laboratory professionals need to be aware of potential interference from increased HbF levels that could adversely affect HbA 1c results.…”

“…Hemoglobin variants and increases in circulating fetal hemoglobin (HbF), defined as HbF>2%, have been reported to interfere with some assay methods for HbA 1c (1–3). In view of the relatively common occurrence of such increases in HbF (~ 1.5% of the US population), and the fact that individuals with increased HbF are usually asymptomatic, it is important to know whether HbA 1c methods show interference and if so, at what level of HbF.…”

Evaluation of haemoglobin A1c measurement by an enzymatic method using an automated analyser that has an on-board haemolysis system

“…Because boronate affinity methods measure the ratio of glycated to total haemoglobin regardless of the Hb species present, it is generally assumed that Hb variants do not interfere with HbA1c results. 11 …”