Diabetology International

, Volume 7, Issue 2, pp 199–203 | Cite as

Detection of hemoglobin variant HbS on the basis of discrepant HbA1c values in different measurement methods

  • Yusuke Takeda
  • Daiji KawanamiEmail author
  • Kazunori Utsunomiya
Case Report


Glycated hemoglobin (HbA1c) is commonly used to assess long-term glycemic control in patients with diabetes mellitus. Numerous conditions, including hemoglobinopathies, can alter HbA1c measurements and cause misleading results. More than 20 methods for determining HbA1c are commercially available to clinical laboratories. Herein, we report a diabetic patient in whom the HbS variant was detected on the basis of discrepant Hb1Ac levels estimated using immunonephelometry or high-performance liquid chromatography (HPLC). The patient, a 48-year-old African man with a 10-year history of type 2 diabetes, was referred to our hospital with an HbA1c level estimated at 13.3 % by immunonephelometry and 7.6 % by HPLC, whereas the glycoalbumin level was 47.5 %. These discrepancies prompted us to carry out genetic sequence analysis in which we identified an A → T transversion in codon 6 of the patient’s HBB gene, corresponding to a predicted E6V substitution (βCD6) characteristic of HbS. Our results indicate that redundant measurements of HbA1c using diverse methods may be useful when the presence of abnormal Hb is suspected.


Abnormal hemoglobin HbS Glycoalbumin HbA1c HPLC Immunonephelometry 


Compliance with Ethical Standards

Human Rights Statement and Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Declaration of Helsinki, 1964, and later versions. Informed consent was obtained for being included in the study.

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Koga M, Suzuki MK, Tanahashi Y. Calculation of HbA1c and glycated albumin from serially measured self-monitored blood glucose in patients with type 1 diabetes mellitus. Clin Chim Acta. 2013;425:188–91.CrossRefPubMedGoogle Scholar
  2. 2.
    John G, English E. IFCC standardized HbA(1c): should we be as one? Clin Chem Lab Med. 2012;50:1243–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Rhea JM, Molinaro R. Pathology consultation on HbA1c methods and interferences. Am J Clin Pathol. 2014;141:5–16.CrossRefPubMedGoogle Scholar
  4. 4.
    Behan KJ, Merschen J. HbA1c does not always estimate average glucose. Clin Lab Sci. 2011;24:71–7.PubMedGoogle Scholar
  5. 5.
    Little RR, Roberts WL. A review of variant hemoglobins interfering with hemoglobin A1c measurement. J Diabetes Sci Technol. 2009;3:446–51.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Friss U, Beck A, Kohne E, Lehmann R, Koch S, Haring HU, Schmuelling RM, Schleicer E. Novel hemoglobin vaiant[beta(E10)Lys → Asn], with decreased oxygen affinity, causes falsely low hemoglobin A1c values by HPLC. Clin Chem. 2003;49:1412–5.CrossRefGoogle Scholar
  7. 7.
    Castelli R, Tempesta A, Bianchi A, Porro T, Ivaldi G, Cappellini MD. Unreliable estimation of HbA due to the presence of Camperdown haemoglobin [beta 104 (G6) Arg → Ser]. Diabet Med. 2004;21:377–9.CrossRefPubMedGoogle Scholar
  8. 8.
    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
  9. 9.
    Watanabe N. Inspection item useful as an index of blood glucose control-purposes and cautions of inspection. Med Technol. 2013;41:153–64 (in Japanese).Google Scholar
  10. 10.
    Jaina N, Kesimer M, Hoyer JD, Calikoglu AS. Hemoglobin Raleigh results in factitiously low hemoglobin A1c when evaluated via immunoassay analyzer. J Diabetes Complicat. 2011;25:14–8.CrossRefGoogle Scholar
  11. 11.
    Kluger R. Red cell substitutes from hemoglobin-do we start all over again? Curr Opin Chem Biol. 2010;14:538–43.CrossRefPubMedGoogle Scholar
  12. 12.
    Yamashiro Y. Identification of hemoglobin variants. Med Technol. 2004;32:565–72 (in Japanese).Google Scholar
  13. 13.
    Masiello D, Heeney MM, Adewoye AH, Eung SH, Luo HY, Steinberg MH, Chui DH. Hemoglobin SE disease-A concise review. Am J Hematol. 2007;82:643–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Lippi G, Mercadanti M, Alberta C, Franchini M. An unusual case of a spurious, transfusion-acquired haemoglobin S. Blood Transfus. 2010;8:199–202.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Harano T. Hemoglobinopathy in Japan: detection and analysis. Rinsho Byori. 1999;47:215–23 (in Japanese).PubMedGoogle Scholar
  16. 16.
    McCurdy PR. 32-DFP and 51-Cr for measurement of red cell life span in abnormal hemoglobin syndromes. Blood. 1969;33:214–24.PubMedGoogle Scholar
  17. 17.
    Takarabe D, Kishimoto M, Tanaka T, Takahashi Y, Kajio H, Harano K, Noda M. Hemoglobin variant HbE found in two south Asian diabetic patients. Intern Med. 2009;48:1397–401.CrossRefPubMedGoogle Scholar
  18. 18.
    Sacks DB. Hemoglobin variants and hemoglobin A1c analysis: problem solved? Clin Chem. 2003;49:1245–12457.CrossRefPubMedGoogle Scholar
  19. 19.
    Rhea JM, Koch D, Ritchie J, Singh HV, Young AN, Burgess T, Molinaro RJ. Unintended reporting of misleading HbA(1c) values when using assays incapable of detecting hemoglobin variants. Arch Pathol Lab Med. 2013;137:1788–91.CrossRefPubMedGoogle Scholar
  20. 20.
    Reeve J, Blake L, Griffin D, O’Shea P. Incidental detection of hemoglobin (Hb) variants during high performance liquid chromatography (HPLC) analysis of HbA1c: is it time for a standardized approach to reporting? Ir J Med Sci. 2015;184:353–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Schnedl WJ, Liebminger A, Roller RE, Lipp RW, Krejs GJ. Hemoglobin varoants and determination of glycated hemoglobin (HbA1c). Diabetes Metab Rev. 2001;17:94–8.CrossRefGoogle Scholar

Copyright information

© The Japan Diabetes Society 2015

Authors and Affiliations

  • Yusuke Takeda
    • 1
  • Daiji Kawanami
    • 1
    Email author
  • Kazunori Utsunomiya
    • 1
  1. 1.Division of Diabetes, Metabolism and Endocrinology, Department of Internal MedicineJikei University School of MedicineTokyoJapan

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