text: Labile Hemoglobin A1c Threshold Is Useful in Identifying the Hemoglobin J Variant, Which Causes Falsely Low Hemoglobin A1c Concentrations | The Journal of Applied Laboratory Medicine
  DOI: 10.1373/jalm.2017.023044 Published October 2017
  Kees C.J. Smeekens
  Laboratory of Clinical Chemistry and Haematology, Amphia Hospital, Breda, the Netherlands.
  For correspondence: KBoonen@amphia.nl
  Hemoglobin (Hb)2 A1c is defined by the IFCC as hemoglobin that is irreversibly glycated at one or both N-terminal valines of the β chain (1). It is produced by a 2-step nonenzymatic process. In the first step, glucose forms a weak, reversible bond with valine; this variant is known as labile HbA1c (LHbA1c). Afterward, the bond becomes irreversible, forming stabile HbA1c (SHbA1c). The rate of HbA1c formation is directly proportional to the glucose concentration. Because of the relatively long lifespan of erythrocytes (120 days on average), HbA1c is a reflection of glucose concentration in the past 3 months and can therefore be used to monitor long-term glycemic control in patients with diabetes mellitus.
  HPLC is often used for the analysis of HbA1c. Different interferences have been described for this method, with one of the most frequent being the presence of hemoglobin variants. Modern analyzers can be programed to produce a "flag" if a variant peak is detected in the spectrum, to alert users that results may be unreliable.
  Although rare in the Caucasian population, HbJ is a relatively common variant in our region in the Netherlands. The reason for this is unknown. HbJ is a group of Hb variants that migrate faster than HbA, but slower than HbI (2), and is known to show interference on HbA1c analysis by HPLC with the Tosoh G8 (Sysmex Bv). Therefore, identifying the presence of this variant is pivotal in our region.
  Because the HbJ fraction has the same retention time as HbA, its presence results in falsely high HbA0 concentration, leading to falsely low HbA1c concentration (since it is expressed as mmol/mol HbA). Strikingly, the labile HbA1c fraction is always very high in these patients, possibly because of the presence of glycated HbJ (Fig. 1). It has previously been shown (on a different analyzer) that the LHbA1c/SHbA1c quotient can be a useful method to identify different variants, among which is HbJ (3).
  Fig. 1. Chromatograms with and without the presence of glycated HbJ.
  (A), Chromatogram of patient with known heterozygous HbJ. Note the high fraction of LHbA1c, compared to a chromatogram of a patient without HbJ (B).
  During validation of the analyzer, only a few fresh samples with known HbJ were analyzed. We therefore set a cutoff for the LHbA1c/SHbA1c quotient based on samples that were negative for HbJ. The mean quotient of these samples was found to be 0.43 (based on 15 samples). After 1 year, review of all confirmed HbJ samples (n = 25) showed that the quotient was always well above 0.7 (mean 0.83). The trigger for the flagging was therefore increased to 0.7. Evaluation after 3 months showed that all our known HbJ-positive patients generated a flag during analysis. Occasionally, patients negative for HbJ show high quotients; these patients had either poor glycemic control or high erythrocyte turnover.
  In conclusion, an LHbA1c/SHbA1c quotient >0.7 in a patient without high erythrocyte turnover or poor glycemic control is highly suspicious for HbAJ phenotype.
  labile HbA1c
  SHbA1c
  stabile HbA1c.
  IFCC standardization of HbA1c. http://www.ngsp.org/docs/IFCCstd.pdf (Accessed December 2016).
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  Peng WK,
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