Evaluation of interference from hemoglobin C, D, E and S traits on measurements of hemoglobin A1c by fifteen methods
Open accessAbstract
BACKGROUND: Hemoglobin C, D Punjab, E or S trait can interfere with hemoglobin A1c (HbA1c) results. We assessed whether they affect results obtained with 15 current assay methods. METHODS: Hemoglobin AA (HbAA), HbAC, HbAD Punjab, HbAE and HbAS samples were analyzed on 2 enzymatic, 4 ion-exchange HPLC and 9 immunoassay methods. Trinity Premier Hb9210 boronate affinity HPLC was the comparative method. An overall test of coincidence of least-squared linear regression lines was performed to determine if HbA1c results were statistically significantly different from those of HbAA samples. Clinically significant interference was defined as >6% difference from HbAA at 6 or 9% HbA1c compared to Premier Hb9210 using Deming regression. RESULTS: All methods showed statistically significant effects for one or more variants. Clinically significant effects were observed for the Tosoh G11 variant mode (HbAD), Roche b 101 (HbAC and HbAE) and Siemens DCA Vantage (HbAE and HbAS). All other methods (Beckman Coulter B93009 and B00389 on DxC700AU, and Unicel DxC, Ortho Clinical Vitros 5.1, Roche cobas c 513, Siemens Dimension RxL and Vista, and Enzymatic on Advia and Atellica, Tosoh G8 5.24 and 5.28, and GX) showed no clinically significant differences. CONCLUSIONS: A few methods showed interference from one or more variants. Laboratories need to be aware of potential HbA1c assay interferences.
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Several hemoglobin variants and chemically modified derivatives of hemoglobin interfere with some assay methods.
“Several hemoglobin variants (e.g., hemoglobins S, C, D, and E) and chemically modified derivatives of hemoglobin interfere with some assay methods (independent of any effects due to shortened RBC survival) (348-350) (for a review, see reference 347).”
From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [349]
The Introduction identifies method-specific interference from hemoglobin S, C, D, and E traits, and the Results report clinically significant interference for some assays. The paper does not address interference from chemically modified hemoglobin derivatives. Page numbers are not available in our copy. (LLM, conf=0.88)
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- Authors
- Rohlfing, C., Hanson, S., Estey, M. P., Bordeleau, P., & Little, R. R.
- Affiliations
- University of Missouri (US)
- Corresponding author
- Rohlfing, Curt
- Venue
- Clinica Chimica Acta
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 522
- Pages
- 31-35
- ISSN
- 0009-8981 (ISSN-L)
- PMC
- PMC8464520
- OpenAlex
- W3188638401
- Semantic Scholar
- 78cd2b2bd5085eca58f1421d2637bf4f9aa6188a
- Cited by
- 30
- References
- 19
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 4 · 2023: 12 · 2022: 6 · 2021: 1
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Clinica Chimica Acta (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases
- University of Missouri
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
- Keywords
- hemoglobin C, hemoglobin D Punjab, hemoglobin E, hemoglobin S, HbA1c, assay interference, ion-exchange HPLC, immunoassay, enzyme activity assay, diabetes monitoring
- MeSH terms
- Chromatography, High Pressure Liquid, Hematologic Tests, Glycated Hemoglobin, Hemoglobin C, Humans, Immunoassay
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