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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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1437-4331
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Volume 55, Issue 8

Issues

Hb variants in Korea: effect on HbA1c using five routine methods

Yeo-Min Yun / Misuk Ji / Dae-Hyun Ko
  • Department of Laboratory Medicine, Hallym University College of Medicine, Dongtan Sacred Heart Hospital, Hwaseong, South Korea
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/ Sail Chun
  • Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
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/ Gye Cheol Kwon
  • Department of Laboratory Medicine, Chungnam National University Hospital, Daejeon, South Korea
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/ Kyunghoon Lee
  • Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
  • Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea
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/ Sang Hoon Song
  • Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea
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/ Moon Woo Seong
  • Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea
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/ Sung Sup Park
  • Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea
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/ Junghan Song
  • Corresponding author
  • Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea
  • Department of Laboratory Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, South Korea, Fax: +82-31-787-4015
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Published Online: 2017-01-20 | DOI: https://doi.org/10.1515/cclm-2016-0865

Abstract

Background:

Quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. We evaluated the impact of various Hb variants on five routine HbA1c assays by comparing with the IFCC reference measurement procedure (RMP).

Methods:

Whole blood samples showing warning flags or no results on routine HPLC HbA1c assays were confirmed for Hb variants and were submitted to HbA1c quantification using Sebia Capillarys 2 Flex Piercing, Roche Tina-quant HbA1c Gen. 2, Bio-Rad Variant II Turbo 2.0, ADAMS HA-8180, Tosoh G8 standard mode, and IFCC RMP using LC-MS.

Results:

Among 114 samples, the most common variants were Hb G-Coushatta (n=47), Queens (n=41), Ube-4 (n=11), Chad (n=4), Yamagata (n=4), G-His-Tsou (n=2), G-Taipei (n=1), Fort de France (n=1), Hoshida (n=1), and two novel variants (Hb α-globin, HBA 52 Gly>Cys and Hb β-globin, HBB 146 His>Asn). In terms of control samples, all the result of HbA1c were “acceptable”, within the criteria of ±7% compared to IFCC RMP target values. However, percentage of “unacceptable” results of samples with Hb variants were 16% for Capillarys 2, 7% for Tina-quant, 51% for Variant II Turbo 2.0, 95% for G8 standard mode, and 89% for HA-8180. The Capillarys 2 and HA-8180 assay did not provide the results in 5 and 40 samples with Hb variants, respectively.

Conclusions:

HbA1c results from five routine assays in patients with relatively common Hb variants in Korea showed various degrees of bias compared to those of IFCC RMP. Therefore, laboratories should be aware of the limitation of their methods with respect to interference from Hb variants found commonly in their local population and suggest an alternative HbA1c quantification method.

This article offers supplementary material which is provided at the end of the article.

Keywords: capillary electrophoresis; HbA1c; HPLC; IFCC reference measurement procedure; immunoassay; variant hemoglobin

References

  • 1.

    The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977–86.PubMedGoogle Scholar

  • 2.

    American Diabetes Association. Standards of medical care in diabetes–2011. Diabetes Care 2011;34(Suppl 1):S11–61.PubMedWeb of ScienceGoogle Scholar

  • 3.

    American Diabetes Association. Standards of medical care in diabetes–2014. Diabetes Care 2014;37(Suppl 1):S14–80.PubMedWeb of ScienceGoogle Scholar

  • 4.

    Little RR, Rohlfing CL, Hanson S, Connolly S, Higgins T, Weykamp CW, et al. Effects of hemoglobin (Hb) E and HbD traits on measurements of glycated Hb (HbA1c) by 23 methods. Clin Chem 2008;54:1277–82.CrossrefGoogle Scholar

  • 5.

    Little RR, Roberts WL. A review of variant hemoglobins interfering with hemoglobin A1c measurement. J Diabetes Sci Technol 2009;3:446–51.PubMedCrossrefGoogle Scholar

  • 6.

    Lin CN, Emery TJ, Little RR, Hanson SE, Rohlfing CL, Jaisson S, et al. Effects of hemoglobin C, D, E, and S traits on measurements of HbA1c by six methods. Clin Chim Acta 2012;413:819–21.CrossrefGoogle Scholar

  • 7.

    Jaisson S, Leroy N, Desroches C, Tonye-Libyh M, Guillard E, Gillery P. Interference of the most frequent haemoglobin variants on quantification of HbA1c: comparison between the LC-MS (IFCC reference method) and three routinely used methods. Diabetes Metab 2013;39:363–9.PubMedCrossrefGoogle Scholar

  • 8.

    Lee ST, Kim MS, Choi DY, Kim SK, Ki CS. Incidence of variant hemoglobin (Hb) and increased fetal Hb concentrations and their effect on Hb A1c measurement in a Korean population. Clin Chem 2006;52:1445–6.CrossrefGoogle Scholar

  • 9.

    Li HJ, Zhao XN, Qin F, Li HW, Li L, He XJ, et al. Abnormal hemoglobins in the Silk Road region of China. Hum Genet 1990;86:231–5.PubMedGoogle Scholar

  • 10.

    Lee ST, Weykamp CW, Lee YW, Kim JW, Ki CS. Effects of 7 hemoglobin variants on the measurement of glycohemoglobin by 14 analytical methods. Clin Chem 2007;53:2202–5.CrossrefWeb of SciencePubMedGoogle Scholar

  • 11.

    Little RR, La’ulu SL, Hanson SE, Rohlfing CL, Schmidt RL. Effects of 49 different Rare Hb Variants on HbA1c Measurement in Eight Methods. J Diabetes Sci Technol 2015;9:849–56.CrossrefPubMedGoogle Scholar

  • 12.

    Lee SC, Wang LH, Tsai SM, Fang HY, Tsai LY. Effects of the Hb E, Hb H and Hb G-Taichung variants on HbA1c values by the Bio-Rad variant II turbo analyzer. Clin Biochem 2011;44:1338–42.CrossrefGoogle Scholar

  • 13.

    Rodríguez-Capote K, Estey MP, Barakauskas VE, Burton T, Holmes D, Krause R, et al. Identification of Hb Wayne and its effects on HbA1c measurement by 5 methods. Clin Biochem 2015;48:1144–50.Web of SciencePubMedCrossrefGoogle Scholar

  • 14.

    Ji L, Yu J, Zhou Y, Xia Y, Xu A, Li W, et al. Erroneous HbA1c measurements in the presence of β-thalassemia and common Chinese hemoglobin variants. Clin Chem Lab Med 2015;53:1451–8.PubMedGoogle Scholar

  • 15.

    Lorenzo-Medina M, De-La-Iglesia S, Ropero P, Nogueira-Salgueiro P, Santana-Benitez J. Effects of hemoglobin variants on hemoglobin a1c values measured using a high-performance liquid chromatography method. J Diabetes Sci Technol 2014;8:1168–76.CrossrefPubMedGoogle Scholar

  • 16.

    Schnedl WJ, Krause R, Wallner SJ, Piswanger-Soelkner C, Lipp RW. Effect of silent hemoglobin variants on A1C measurement with the IFCC reference method and 6 routine methods. Clin Chim Acta 2008;398:161–2.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 17.

    Lenters-Westra E, Strunk A, Campbell P, Slingerland RJ. Can the afinion HbA1c point-of-care instrument be an alternative method for the Tosoh G8 in the case of Hb-Tacoma? Scand J Clin Lab Invest 2016:1–6.Web of ScienceGoogle Scholar

  • 18.

    Kaiser P, Akerboom T, Molnar P, Reinauer H. Modified HPLC-electrospray ionization/mass spectrometry method for HbA1c based on IFCC reference measurement procedure. Clin Chem 2008;54:1018–22.CrossrefPubMedGoogle Scholar

  • 19.

    Bry L, Chen PC, Sacks DB. Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clin Chem 2001;47:153–63.PubMedGoogle Scholar

  • 20.

    Kabytaev K, Connolly S, Rohlfing CL, Sacks SB, Stoyanov AV, Little RR. Higher degree of glycation of hemoglobin S compared to hemoglobin A measured by mass spectrometry: Potential impact on HbA1c testing. Clin Chim Acta 2016;458:40–4.CrossrefPubMedGoogle Scholar

  • 21.

    Cheng X, Li M, Wu J, Su W. HbG-Coushatta: an unexpected discovery during HbA1c measurement. Clin Chim Acta 2015;444:163–6.CrossrefWeb of SciencePubMedGoogle Scholar

About the article

Received: 2016-09-28

Accepted: 2016-12-14

Published Online: 2017-01-20

Published in Print: 2017-07-26


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: This study was supported by a grant (no. 06-2013-231) from the SNUBH Research Fund.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 55, Issue 8, Pages 1234–1242, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2016-0865.

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