Unexpected Hemoglobin A1c Results

Abstract

A 52-year-old woman with a medical history of hepatitis B, hyperlipidemia, hypertension, anemia, and depression presented to the internal medicine clinic for a routine visit. Laboratory tests 3 months previously had revealed an impaired fasting glucose concentration of 5.9 mmol/L (106 mg/dL) [reference interval, 3.9–5.6 mmol/L (70–100 mg/dL)]. Therefore, a hemoglobin (Hb)2 A1c analysis was performed. The initial Hb A1c evaluation by cation-exchange HPLC (CE-HPLC) (Hb A1c Program on the VARIANT II TURBO Link System; Bio-Rad Laboratories) showed an Hb A1c value of 115.8% (reference interval, 4.0%–6.0%) (Fig. 1). Fig. 1. CE-HPLC chromatogram for Hb A1c analysis. Hb S and an aberrant Hb A1c value of 115.8% represented the predominant Hb peaks in the chromatogram. In an effort to determine if the unusual Hb A1c result was due to potential hemoglobinopathies, we performed an Hb variant analysis with the Bio-Rad VARIANT CE-HPLC β-Thalassemia Short Program. The analysis revealed the absence of Hb A and the presence of sickle cell Hb (Hb S) (37.4%), along with normal Hb A2 (3.2%) and Hb F (<1.0%) (Fig. 2). Also evident was another large peak (53.0%) that eluted earlier than Hb A, which we called P2. This study suggested the presence of an Hb variant with a chromatographic retention time virtually identical to that of Hb A1c, in addition to Hb S (Figs. 1 and 2). A subsequent Hb electrophoretic analysis at pH 6.0 (QuickGel Acid; Helena Laboratories) identified Hb S and another abnormal band with a mobility similar to Hb F (not shown). Fig. 2. Chromatogram of Hb variants analysis with the CE-HPLC β-Thalassemia Short Program. Hb S (37.4%), wild-type Hb A2 (3.2%), and Hb F (<1.0%) were identified, but Hb A was not detected. A large peak, which we designated P2, was detected at 53.0%. ### PATIENT FOLLOW-UP To identify the Hb variants, we investigated DNA sequences corresponding to the patient's β-globin genes. This …