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      Hemoglobin variants detected by hemoglobin A1c (HbA1c) analysis and the effects on HbA1c measurements

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          Abstract

          Background:

          Hemoglobin (Hb) A1c is a tool widely used to monitor long-term glycemic control in diabetic patients. The objective of our study is to compare the HbA1c values measured on high performance liquid chromatography (HPLC) and immunoassay in patients who were detected to have hemoglobin variant after HbA1c analysis.

          Materials and Methods:

          We compared the HbA1c values measured using the Arkray Adams A1c HA-8160 (HPLC method) and Roche Cobas Integra (immunoturbidimetric method) from diabetic patients who were diagnosed with hemoglobin variants.

          Results:

          Forty-three diabetic patients were diagnosed with hemoglobin variants: 13 elevated Hb F, 12 Hb E trait, seven Hb S trait, seven Hb D trait, two Hb E / beta-Thalassemia, one Hb C trait, and one homozygous Hb S.

          Conclusion:

          Knowledge of hemoglobin variants affecting HbA1c measurements is essential, in order to avoid mismanagement of diabetic patients.

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          Most cited references17

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          Effects of hemoglobin C and S traits on glycohemoglobin measurements by eleven methods.

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            Effects of hemoglobin (Hb) E and HbD traits on measurements of glycated Hb (HbA1c) by 23 methods.

            Glycohemoglobin (GHB), reported as hemoglobin (Hb) A(1c), is a marker of long-term glycemic control in patients with diabetes and is directly related to risk for diabetic complications. HbE and HbD are the second and fourth most common Hb variants worldwide. We investigated the accuracy of HbA(1c) measurement in the presence of HbE and/or HbD traits. We evaluated 23 HbA(1c) methods; 9 were immunoassay methods, 10 were ion-exchange HPLC methods, and 4 were capillary electrophoresis, affinity chromatography, or enzymatic methods. An overall test of coincidence of 2 least-squares linear regression lines was performed to determine whether the presence of HbE or HbD traits caused a statistically significant difference from HbAA results relative to the boronate affinity HPLC comparative method. Deming regression analysis was performed to determine whether the presence of these traits produced a clinically significant effect on HbA(1c) results with the use of +/-10% relative bias at 6% and 9% HbA(1c) as evaluation limits. Statistically significant differences were found in more than half of the methods tested. Only 22% and 13% showed clinically significant interference for HbE and HbD traits, respectively. Some current HbA(1c) methods show clinically significant interferences with samples containing HbE or HbD traits. To avoid reporting of inaccurate results, ion-exchange chromatograms must be carefully examined to identify possible interference from these Hb variants. For some methods, manufacturers' instructions do not provide adequate information for making correct decisions about reporting results.
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              Silent hemoglobin variants and determination of HbA(1c) with the high-resolution program of the HPLC HA-8160 hemoglobin analyzer.

              Evaluation of HbA1c determination with an automated ion-exchange high-performance liquid chromatography (HPLC) method in patients with clinically silent hemoglobin (Hb) variants. HbA1c values were determined with the Arkray HA-8160 ion-exchange HPLC using the high-resolution, 4.2-min beta-thalassemia screening mode in patients with silent hemoglobin (Hb) variants, namely, Hb Graz, Hb Sherwood Forest, Hb O Padova, and HbD. All of these hemoglobin variants caused additional peaks in the chromatograms, without HbA1c results in patients with Hb Graz and Hb Sherwood Forest, and demonstrated extra peaks with HbA1c results that were clinically too low for patients with Hb O Padova and in the patient with HbD. The development of this automated HPLC method modification with high-resolution beta-thalassemia screening mode aids identification of interference due to some clinically silent Hb variants in HbA(1c) determination.

                Author and article information

                Journal
                Int J Diabetes Dev Ctries
                IJDDC
                International Journal of Diabetes in Developing Countries
                Medknow Publications (India )
                0973-3930
                1998-3832
                Apr-Jun 2010
                : 30
                : 2
                : 86-90
                Affiliations
                Department of Pathology, Faculty of Medicine, University of Malaya, Malaysia
                [1 ]Division of Laboratory Medicine, University Malaya Medical Center, 50603 Kuala Lumpur, Malaysia
                Author notes
                Correspondence to: Dr. M. Thevarajah, Department of Pathology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. E-mail: tmalathi@ 123456um.edu.my
                Article
                IJDDC-30-86
                10.4103/0973-3930.62598
                2878696
                20535312
                a7e778d1-f549-4ded-84f2-9c896640bdcc
                © International Journal of Diabetes in Developing Countries

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 March 2009
                : 04 March 2010
                Categories
                Original Article

                Endocrinology & Diabetes
                hemoglobin variants,immunoassay,hba1c,high performance liquid chromatography

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