Inconsistent Hb A1c Results Observed after Implementing a New Method

Summary

Student discussion

Song Lu, Terri Neibauer, Eric Saylor, Bonifacio Dewasse, and Yusheng Zhu

Case description

A 66-year-old White male with a history of type 2 diabetes mellitus (T2DM), congestive heart failure, and chronic kidney disease visited an outpatient clinic for regular follow-up with T2DM and congestive heart failure. A hemoglobin A_1c (Hb A_1c) test was performed using Sebia CAPI3 TERA capillary electrophoresis (CE) and the apparent Hb A_1c was 9.1% (normal range 4.0–6.0%) with an unknown peak cathodal to Hb A₀. This peak partially overlapped with Hb A₀ and had a similar size. The patient had no history of anemia or related symptoms at the time of the visit. Because of this atypical profile, the Hb A_1c result was not reported, and the case was further investigated. The concurrent fasting glucose concentration was 156 mg/dL (8.7 mmol/L) [normal range: 70–100 mg/dL (3.9–5.6 mmol/L)], and the fasting glucose concentrations ranged from 110 mg/dL (6.1 mmol/L) to 156 mg/dL (8.7 mmol/L) with an average of 135 mg/dL (7.5 mmol/L) in the past 3 months. The patient’s previous Hb A_1c and fasting glucose concentration were 6.4% and 124 mg/dL (6.9 mmol/L), tested 6 months prior. HbA_1c was measured by a cation exchange HPLC method (Tosoh G8, v.5.24F) at that time, and no atypical pattern or hemoglobin variant was detected.

Since the unknown hemoglobin variant was in the zone of Hb F, there was a concern for potential interference with Hb A_1c quantification (i.e., if Hb F > 23% as per the manufacturer’s instructions). To determine whether the variant hemoglobin was Hb F, the specimen was tested for hemoglobin variants using CE (Sebia Capillarys 2, hemoglobin program). A similar peak overlapping with Hb A was identified, but it was not in the Hb F zone. According to Sebia’s user manual, the variant peak was in a zone that did not contain any common pathological variants. For a comparison with the previous HPLC method, we also measured the Hb A_1c of this specimen by Tosoh G8, and the result was 5.8% without any hemoglobin variants.