Journal of Medical Surgical and Allied Sciences, Volume 2, Issue 1 : 1-6. Doi : 10.37446/jmedsurg/cr/2.1.2024.1-6
Case Report

OPEN ACCESS | Published on : 30-Jun-2024

Discordantly low hemoglobin A1c in the context of marked hyperglycemia

  • Mustafa Ibrahim Abbas
  • Department of Hematology and Immunohematology, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Medani, Sudan.
  • Mubarak Ahmed Elshafia
  • Department of Hematology and Immunohematology, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Medani, Sudan.
  • Khalid Abdelsamea Mohamedahmed
  • Department of Hematology and Immunohematology, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Medani, Sudan.; Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jerash University, Jerash, Jordan. khalid.gu89@gmail.com. ORCID No: 0000-0001-7084-6106.
  • Yousif Abdelhameed Mohammed
  • Department of Clinical Chemistry, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Medani, Sudan.
  • Sarah Hameed Aldhafiri
  • Clinical Laboratory Department, Collage of Applied Medical Science, University of Hafr Albatin, Hafr Albatin, Saudi Arabia.
  • Fayhaa Mahmood Madani Hamood
  • Department of Medicine, Wad Medani Teaching Hospital, Wad Medani, Sudan.
  • Mazza Alsayed Adam
  • Department of Medical Laboratories, Almumayaz Advance Medical Laboratories, Wad Medani, Sudan.
  • Omar Osman Mohamed
  • Department of Medical Laboratories, Almumayaz Advance Medical Laboratories, Wad Medani, Sudan.
  • Ahmed Mohamed Ahmed
  • Department of Medical Laboratories, Almumayaz Advance Medical Laboratories, Wad Medani, Sudan.

Abstract

Background: Hemoglobin A1c (HbA1c) acts as the primary biomarker for evaluating long-term glucose regulation. Nevertheless, high concentrations of fetal hemoglobin (HbF) can affect the accuracy of HbA1c assays in a manner dependent on the method used, possibly leading to falsely low HbA1c readings even when there is considerable hyperglycemia.

Case Presentation: The outpatients showed significant hyperglycemia (random blood glucose: 433 mg/dL) and highly positive urine ketones (+++), aligning with a diagnosis of diabetic ketoacidosis. Ironically, HbA1c obtained through standard immunoassay was 6.5%, which is categorized within the non-diabetic range. Follow-up hemoglobin fractionation showed an increased fetal hemoglobin (HbF) concentration of 4.1%, causing worry about assay interference and leading to a reassessment of the HbA1c outcome.

Conclusion: Elevated fetal hemoglobin (>4%) can falsely lower HbA1c, especially with immunoassay or boronate-affinity methods. Ion-exchange HPLC or electrophoresis is recommended, and clinicians should integrate alternative glycemic markers or continuous glucose monitoring to guide management accurately.

Keywords

hemoglobin A1c, fetal hemoglobin, HbF interference, Ion-exchange HPLC, capillary electrophoresis, glycemic markers

References

  • Abdalla, A. A., Elmukashfi, S. T. A., Hassan, A. Y., Dafalla, A., & Abdelsamea, K. (2023). The Effect of Aspirin on HbA1c Assay Among Diabetic Hypertensive Patients Attending Abu Aqulah Centre in Wad Madani, Gezira State, Sudan. International Journal of Diabetes and Endocrinology, 8(1), 1–5.

    Ahmed, A. K., Elsiddig, Y. M., Mohamedahmed, K. A., Gamar, S. Y., Mohammed, Y. A., Alfaham, Z. H., & Elamin, M. B. (2022). Assessment of G6PD Activity among Diabetic Patients and Its Relationship with Hyperglycemia, Wad Madani, Gezira State, Sudan. Open Access Library Journal, 9, Article e9399.

    Gallagher, E. J., Le Roith, D., & Bloomgarden, Z. (2009). Review of hemoglobin A(1c) in the management of diabetes. J Diabetes, 1(1), 9–17.

    Galarneau, G., Palmer, C. D., Sankaran, V. G., Orkin, S. H., Hirschhorn, J. N., & Lettre, G. (2010). Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation. Nat. Genet., 42(12), 1049–1051.

    Harris, N. S., Weaver, K. D., Beal, S. G., & Winter, W. E. (2021). The Interaction between Hb A1C and Selected Genetic Factors in the African American Population in the USA. J. Appl. Lab Med., 6(1), 167–179.

    Ibrahim, R. E., Ibrahim, S. E., Abdalsamea, K., Haj Alzebar, A. B., Babiker, A. M., & Nour, B. Y. M. (2021). Evaluation of Common Coagulation Tests in Type 2 Diabetic Patients and Association with Diabetic Pre-cardiovascular Complications, Gezira State–Sudan, 2020-2021. Asian Hematology Research Journal, 5(4), 1–6.

    Jeppsson, J. O., Kobold, U., Barr, J., Finke, A., Hoelzel, W., Hoshino, T., Miedema, K., Paroni, R., Penders, J., Schimmel, H. G., & Weykamp, C. (2016). Approved IFCC reference method for the measurement of HbA1c in human blood. Biochemia Medica, 26(3), 39–44.

    Little, R. R., Rohlfing, C. L., Hanson, S. E., Schmidt, R. L., Lin, C. N., Madsen, R. W., & England, J. D. (2012). The effect of increased fetal hemoglobin on 7 common Hb A1c assay methods. Clin. Chem., 58(5), 945–947.

    Nitta, T., Yamashiro, Y., Hattori, Y., Ezumi, T., Nishioka, M., & Nakamura, J. (2015). The interference by HbF on HbA1c (BM Test HbA1c) measurement in enzymatic method. Ann. Clin. Biochem., 52(Pt 5), 569–575.

    Satpathi, T., Mohan, V., & Unnikrishnan, R. (2022). An Unusual Case of Non-Measurable Glycosylated Hemoglobin (HbA1c) by High-Performance Liquid Chromatography in a Type 2 Diabetes. Journal of Diabetology, 13(1), 129–132.

    Weykamp, C., Miedema, K., Penders, J., & Schimmel, H. G. (2016). Erroneous HbA1c results in a patient with elevated HbC and HbF. Clin. Chim. Acta., 462, 153–157.