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

Abstract

To the Editor: Hemoglobin variants and increases in circulating fetal hemoglobin (Hb F),1 (defined as an Hb F level >2%) have been reported to interfere with some assay methods for Hb A1c (1–3). In view of the relatively common occurrence of such Hb F increases (approximately 1.5% of the US population) and the fact that individuals with an increased Hb F level are usually asymptomatic, it is important to know whether Hb A1c methods show Hb F interference and, if so, at what level of Hb F. In this report, we evaluate the presence of Hb F interference with several HPLC methods. This study was approved by the Institutional Review Board of the University of Utah and Johns Hopkins Medical Institutional Review Board, where the samples originated. The following commercial HPLC methods were evaluated: the G7 and G8 Variant Mode (Tosoh Bioscience); the D-10™ Hemoglobin A1c Program (D-10), the VARIANT™ II Hemoglobin A1c Program (VII NU), the VARIANT™ II TURBO Hemoglobin A1c Program (VII Turbo), and the VARIANT™ II TURBO HbA1c Kit – 2.0 (VII Turbo 2.0) (all Bio-Rad Laboratories); and the ultra2™ A1c boronate affinity method (ultra2) (Trinity Biotech). The Hb F level was estimated from the G7 or G8 Hb F percentage. A small number of samples (n = 24) with and without an increased Hb F level were analyzed by both the IFCC capillary electrophoresis (CE) method (4) and the G7 method to verify …