Labile hemoglobin A1c: unexpected indicator of preanalytical contraindications.

Labile hemoglobin A 1c (Hb A 1c), or pre–Hb A 1c , is an intermediate in the synthesis of Hb A 1c and is characterized by the reversible binding of glucose to Hb as a Schiff base (1). Its biological variation is related to recent fluctuations in glycemia and cannot provide suitable retrospective information on a patient's long-term glycemic balance. Therefore, labile Hb A 1c must be eliminated from the measured Hb A 1c over the 6 – 8 weeks before sampling in order to estimate the quality of diabetic control (2, 3). Most of the Hb A 1c methods available on the market either are insensitive to labile Hb A 1c (e.g., immunologic assays, affinity assays) or separate or even eliminate it during analysis (e.g., by HPLC or low-pressure liquid chromatography) (4). It might be of interest, however, to take labile Hb A 1c values into account when interpreting Hb A 1c results if an HPLC system capable of separating this fraction can be used. In some circumstances , measurements of labile Hb A 1c might serve to detect preana-lytical problems that could lead to inappropriate clinical decisions. We report on 2 recent Hb A 1c orders our laboratory received without any specific information from the clinical units. We used HPLC analysis to assay Hb A 1c (Variant II analyzer equipped with the Variant II Hemoglobin A1C NU Kit; Bio-Rad Laboratories); the assay fulfilled analytical specifications. We noted discrepancies, however, in each sample between Hb A 1c values that fell within the reference interval or were slightly increased and labile Hb A 1c values that were substantially increased. Although no reference intervals for labile Hb A 1c are currently available in the literature, we found the mean (SD) percentage of labile Hb A 1c to be 0.95% (0.26%) of the total Hb in 100 diabetic patients with stable Hb A 1c values between 4% and 6% (i.e., 20 – 42 mmol/mol). We considered the level of labile Hb A 1c to be high when it was Ͼ1.5% (i.e., mean ϩ 2 SDs). Table 1 summarizes the initial information we obtained from the clinical units. The first patient had a history of diabetes mellitus with a mean Hb A 1c value of 8.0% (64 mmol/mol). The Hb A 1c value in this patient was 5.8% (40 mmol/ mol), whereas the labile Hb A 1c value was 3.1%. The second patient …