Hb I: A α‐globin chain variant causing unexpected HbA<sub>1c</sub> results

Xu, Anping; Sun, Jian; Li, Jie; Chen, Weidong; Zheng, Ruoyang; Han, Zhong-Hou; Ji, Ling

doi:10.1002/jcla.22671

Cited by 6 publications

(5 citation statements)

References 8 publications

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“…An unusually low level of HbA1c or discordance between blood sugar and HbA1c values should alert clinicians to the possibility of Hb variants. Since the effect of a particular Hb variant on HbA1c results is frequently method-dependent (e.g., ion-exchange HPLC methods are frequently affected by the presence of Hb variants), repeat analysis should ideally be performed using an alternative method based on a different analytical principle from the initial assay ( 14 ); these alternative methods may include electrophoresis, immunoassays and enzymatic analysis. Among the methods, the principle of electrophoresis is based on the fact that colloidal particles with different electric charges under certain conditions move through an electric field by electrostatic attraction, which may identify abnormal Hb ( 12 ).…”

Section: Discussionmentioning

confidence: 99%

HbA mutation causing false‑normal HbA1c results determined by HPLC in a patient with type 2 diabetes mellitus: A case report

Wang

et al. 2021

Exp Ther Med

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Glycated hemoglobin A1c (HbA1c) is a convenient measure of long-term blood glucose concentrations and it is an accepted diagnostic test for type 2 diabetes mellitus (T2DM). The present study reported on a female patient with T2DM, whose fasting blood glucose and glycated albumin levels were elevated, while the HbA1c levels were in the normal range, which was inconsistent with the patient's clinical diagnosis. In the subsequent analysis, genomic DNA was extracted from the patient's blood and the HbA genes were analyzed by Sanger sequencing. The results indicated that the patient's HbA α1/2-chain genes had no mutations, while two HbA β-chain gene mutations were present, including an HBB:c.9T>C variant and a Hb G-Coushatta variant. The HBB:c.9T>C variant is a silent mutation that has no effect on HbA1c levels when detected by ion-exchange high-performance liquid chromatography (HPLC), while the Hb G-Coushatta variant may cause a discrepancy between blood glucose control and HbA1c levels when detected by ion-exchange HPLC. These results suggested that the Hb G-Coushatta variant gave rise to the false-normal result regarding HbA1c levels when detected by ion-exchange HPLC that was inconsistent with the clinical manifestations in this patient.

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Section: Discussionmentioning

confidence: 99%

HbA mutation causing false‑normal HbA1c results determined by HPLC in a patient with type 2 diabetes mellitus: A case report

Wang

et al. 2021

Exp Ther Med

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“…Dessi et al showed that capillary electrophoresis analyzer is more suitable for HbA1c assay in hemoglobin variant samples compared to HPLC system (20). Xu et al observed that alpha globin chain variant caused unusually high HbA1c levels in a Chinese patient (21). One study showed that HbA1c levels were significantly low in patients with αthalassemia with one functional α-gene (Hb H disease) compared with controls (22).…”

Section: Discussionmentioning

confidence: 99%

Unexpected Detection of Abnormal Hemoglobin Variants During Routine HbA1c Analysis by HPLC Technique: Challenges and Opportunities in HbA1c Testing

Sreedevi

Kumar

Chendar

et al. 2021

Avicenna J Med Biochem

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Background: Glycated Hemoglobin A1c (HbA1c) assay is most widely used in diabetic patients for assessing long-term control of glycemia. The presence of hemoglobin variants may be an incidental finding and can interfere with HbA1c measurements. The aim of the present study is to investigate the prevalence and impact of interference of different abnormal hemoglobin variants on HbA1c measurements during routine HbA1c testing. Methods: A total of 12,092 HbA1c samples were collected from January to August 2018. HbA1c quantification was carried out on a Variant II Bio-Rad’s HPLC analyzer. Abnormal chromatograms were further analyzed using the extended-run high-pressure liquid chromatography (HPLC) analysis in the A2/F mode. Results: The samples were examined for presence of abnormal variants. Samples producing abnormal chromatograms were further analyzed in A2/F mode to characterize hemoglobin variants. Abnormal variants were identified in 126 (1%) samples, and 74 (0.59%) sickle cell traits (SCT) were the most common variant in our findings. Moreover, 30 (0.24%) cases were eluted in the variant window in A1c mode, which on further analysis were found to be Hb E & Hb D traits. Furthermore, 3 (0.02%) cases were eluted at a RT <1 min as (unknown) and identified as Hb H. Also,19 (0.15%) samples were eluted in the P3 window at different retention times. Conclusion: Observing each chromatograph after the analysis can help us in identifying silent hemoglobin variants in routine HbA1c testing. Knowledge and awareness of common hemoglobin variants affecting measurement of HbA1c is imperative to avoid reporting of falsely low HbA1c values in diabetic population.

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“…Some studies used both boronate affinity and cation exchange HPLC systems as the reference when assessing HbA1c concentration 22,23 . The UK Biobank has used and certified the Variant™ II Turbo analyzer as the reference method for HbA1c measurement 24 .…”

Section: Methodsmentioning

confidence: 99%

“…7 Some studies used both boronate affinity and cation exchange HPLC systems as the reference when assessing HbA1c concentration. 22,23 The UK Biobank has used and certified the Variant™ II Turbo analyzer as the reference method for HbA1c measurement. 24 Since TMC Biobank uses the UK Biobank protocol as the reference standard, 17 we then change to Variant™ II Turbo analyzer for HbA1c analysis.…”

Section: Hba1c Measurementmentioning

confidence: 99%

Stability of glycated haemoglobin (HbA1c) measurements from whole blood samples kept at −196°C for seven to eight years in The Malaysian Cohort study

Abdullah

Goh

Othman

et al. 2023

Clinical Laboratory Analysis

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Objective Glycated haemoglobin (HbA1c) is a standard indication for screening type 2 diabetes that also has been widely used in large‐scale epidemiological studies. However, its long‐term quality (in terms of reproducibility) stored in liquid nitrogen is still unknown. This study is aimed to evaluate the stability and reproducibility of HbA1c measurements from frozen whole blood samples kept at −196°C for more than 7 years. Methods A total of 401 whole blood samples with a fresh HbA1c measurement were randomly selected from The Malaysian Cohort's (TMC) biobank. The HbA1c measurements of fresh and frozen (stored for 7–8 years) samples were assayed using different high‐performance liquid chromatography (HPLC) systems. The HbA1c values of the fresh samples were then calculated and corrected according to the later system. The reproducibility of HbA1c measurements between calculated‐fresh and frozen samples was assessed using a Passing‐Bablok linear regression model. The Bland–Altman plot was then used to evaluate the concordance of HbA1c values. Results The different HPLC systems highly correlated (r = 0.99) and agreed (ICC = 0.96) with each other. Furthermore, the HbA1c measurements for frozen samples strongly correlate with the corrected HbA1c values of the fresh samples (r = 0.875) with a mean difference of −0.02 (SD: −0.38 to 0.38). Although the mean difference is small, discrepancies were observed within the diabetic and non‐diabetic samples. Conclusion These data demonstrate that the HbA1c measurements between fresh and frozen samples are highly correlated and reproducible.

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Hb I: A α‐globin chain variant causing unexpected HbA_1c results

Abstract: An unusually high HbA or discordance between blood sugar and HbA values should alert about the possibilities of hemoglobin variants.

Cited by 6 publications

References 8 publications

HbA mutation causing false‑normal HbA1c results determined by HPLC in a patient with type 2 diabetes mellitus: A case report

HbA mutation causing false‑normal HbA1c results determined by HPLC in a patient with type 2 diabetes mellitus: A case report

Unexpected Detection of Abnormal Hemoglobin Variants During Routine HbA1c Analysis by HPLC Technique: Challenges and Opportunities in HbA1c Testing

Stability of glycated haemoglobin (HbA1c) measurements from whole blood samples kept at −196°C for seven to eight years in The Malaysian Cohort study

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Hb I: A α‐globin chain variant causing unexpected HbA1c results

Abstract: An unusually high HbA or discordance between blood sugar and HbA values should alert about the possibilities of hemoglobin variants.

Cited by 6 publications

References 8 publications

HbA mutation causing false‑normal HbA1c results determined by HPLC in a patient with type 2 diabetes mellitus: A case report

HbA mutation causing false‑normal HbA1c results determined by HPLC in a patient with type 2 diabetes mellitus: A case report

Unexpected Detection of Abnormal Hemoglobin Variants During Routine HbA1c Analysis by HPLC Technique: Challenges and Opportunities in HbA1c Testing

Stability of glycated haemoglobin (HbA1c) measurements from whole blood samples kept at −196°C for seven to eight years in The Malaysian Cohort study

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Hb I: A α‐globin chain variant causing unexpected HbA_1c results