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Where Has All the Hemoblobin [A.sub.1c] Gone?


A 43-year-old woman visited her family physician for a routine checkup. Her hemoglobin [A.sub.1c] (Hb [A.sub.1c]) was undetectable and was confirmed by repeat analysis (G8, Tosoh Bioscience). Hemoglobin variant analysis was also performed (Fig. 1). The patient had mild macrocytic anemia. The sample was grossly hemolyzed.


1. What can cause very low or undetectable Hb [A.sub.1c]?

2. How should patients with very low or undetectable Hb [A.sub.1c] be followed?


Depending on the method, factors such as hemoglobinopathies, high red blood cell turnover (i.e. shortened erythrocyte survival), increased fetal hemoglobin, carbamylated hemoglobin, iron replacement therapy, and transfusion requirements may interfere with Hb [A.sub.1c] measurement (1-3).

Hemoglobin variant analysis performed on an ultra2 analyzer showed the presence of 15.7% HbF (peak 2) and 76.3% HbS (peak 5) (Fig. 1). The absence of Hb [A.sub.1c] was due to the absence of HbA in this patient.

In diabetic patients with these conditions, alternative methods such as fructosamine, glycated serum albumin, or self-monitoring of blood glucose should be considered (2, 4).

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

Authors' Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.

Acknowledgments: We would like to thank Goncagul Haklar from Marmara University for her support, comments, and suggestions.


(1.) Bry L, Chen PC, Sacks DB. Effects of hemoglobin variants and chemically modified derivatives on assaysfor glycohemoglobin. Clin Chem 2001; 47:153-63.

(2.) Nasir NM, Thevarajah M, Yean CY. Hemoglobin variants detected by hemoglobin A1c (HbA1c) analysis and the effects on HbA1c measurements. Int J Diabetes Dev Ctries 2010; 30:86-90.

(3.) National Glycohemoglobin Standardization Program. HbA1c assay interferences. (Accessed March 2016).

(4.) Higgins T, Stewart D, Boehr E. Challenges in HbA1c analysis and reporting: an interesting case illustrating the many pitfalls. Clin Biochem 2008; 41:1104-6.

Fethullah Gerin * and Can Sezgin *

Public Health Core Laboratory, Istanbul, Turkey.

* Address correspondence to F.G. at Public Health Core Laboratory, Acelya Cad. Saatli Bina Is Merkezi No:1, Beylikduzu, Istanbul, Turkey. E-mail C.S. at Public Health Core Laboratory, Acelya Cad. Saatli Bina Is Merkezi No:1, Beylikduzu, Istanbul, Turkey. E-mail

Received March 24, 2016; accepted April 29, 2016.

DOI: 10.1373/clinchem.2016.257758

Caption: Fig. 1. Chromatogram for the patient performed on an ultra2 analyzer (TrinityBiotech) shows the presence of 15.7% HbF (peak 2) and 76.3% HbS (peak5).

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Title Annotation:What Is Your Guess?
Author:Gerin, Fethullah; Sezgin, Can
Publication:Clinical Chemistry
Date:Oct 1, 2016
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