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The impact of biotin interference on laboratory testing and patient diagnosis in clinical practice

2019; Future Science Ltd; Volume: 4; Issue: 1 Linguagem: Inglês

10.4155/ipk-2019-0001

2053-0854

Luca Giovanella,

Biosimilars and Bioanalytical Methods

International Journal of PharmacokineticsVol. 4, No. 1 EditorialOpen AccessThe impact of biotin interference on laboratory testing and patient diagnosis in clinical practiceLuca GiovanellaLuca Giovanella*Author for correspondence: Tel: +41 91 811 8672; E-mail Address: Luca.Giovanella@eoc.chClinic for Nuclear Medicine & Competence Centre for Thyroid Diseases, Imaging Institute of Southern Switzerland/Ente Ospedaliero Cantonale, Via Ospedale 6, 6500 Bellinzona, SwitzerlandPublished Online:26 Jul 2019https://doi.org/10.4155/ipk-2019-0001AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInReddit Keywords: biotinclinical practicelaboratory errorslaboratory testingimmunoassayinterferenceBiotin-streptavidin coupling has been utilized for decades by diagnostic immunoassay manufacturers. However, concerns have been raised regarding the risk of biotin interference with biotin/streptavidin-based immunoassays due to the use of high-dose biotin in cosmetic supplements, and treatments for multiple sclerosis [1–4], and some inherited metabolic diseases (e.g., biotinidase, multiple carboxylase and holocarboxylase synthetase deficiencies) [5]. A recent study characterized the biotin pharmacokinetic profile in healthy participants following high-dose biotin administration and provided guidance on washout periods to avoid false assay results from biotin interference [6].Here, we discuss the prevalence of assay interferences, particularly biotin interference, consider its impact on clinical practice, and suggest potential strategies to reduce this impact and ensure accurate patient diagnosis.Incidence & types of laboratory errorsThe total laboratory testing error rate is estimated to vary widely from 0.012 to 0.6% [7]. Most errors occur in the preanalytical phase (e.g., inappropriate sample collection/handling; up to 68% of total errors), followed by the postanalytical phase (e.g., erroneous data entry/reporting; up to 47% of total errors); analytical errors (e.g., interference from endogenous/exogenous substances) constitute 7–13% of total errors, with errors caused by interferences comprising a small proportion of these [8].Immunoassays are susceptible to many interferences. Although it is difficult to estimate the overall frequency with which interferences occur [7], hemolysis is thought to be the leading cause of unsuitable samples for analysis (40–70% of cases) [9]. Importantly, the prevalence of clinically relevant interferences can be substantially lower than the overall interference prevalence. For example, prevalence estimates for human antimouse antibodies range from 30 ng/ml was only 0.5%. Therefore, very few of these biotin concentrations would likely lead to clinical misclassification. The misclassification risk due to biotin interference can vary considerably between assays, and a combination of high peak biotin concentrations and a sensitive assay is needed for a clinically relevant interference to occur; for example, biotin interference thresholds for cardiac troponin assays range from 2.5 to 10,000 ng/ml [17,18]. Although most Roche Diagnostics assays are minimally affected at biotin concentrations of 15.6 and 31.3 ng/ml (simulating 5 and 10 mg biotin intake, respectively), some assays exhibit greater sensitivity, including troponin T, thyroid-stimulating hormone and antithyroid antibodies [18]. Regarding troponin T, a recent study showed that elevated biotin (>20 ng/ml) is rare in US patients with suspected acute coronary syndrome and the likelihood of false-negative acute myocardial infarction prediction due to biotin interference with the Elecsys® Troponin T Gen 5 assay was very low (0.026%), having a minimal effect on the assay's negative predictive value (93.4%) at 3 h [19]. It is important to note that the benefit of diagnostic immunoassay testing largely outweighs the risk of potential misclassification of patients due to interferences, including biotin interference, and laboratory error rates are considerably lower than those seen in overall clinical healthcare [20].Strategies to reduce the risk of biotin interferenceLaboratory staff and clinicians should be aware of the risk for biotin interference, paying particular attention to results from certain patient groups (e.g., patients with multiple sclerosis) or results that do not fit the overall clinical picture. A focus on increased reporting and education on biotin interference, as recommended by the US FDA [2], will hopefully improve awareness and reduce the likelihood of errors occurring. There is also increasing emphasis on education around biotin interference in the multiple sclerosis patient population, with participants in trials of high-dose biotin receiving a card detailing their involvement and the risk for assay interference. This approach has been extended to wider patient groups not directly involved in these trials. However, the need to raise awareness should be balanced against the fact that the risk of clinically relevant misclassification due to biotin interference is low and the overall laboratory error rate has fallen in the past few decades [8]. If biotin interference is suspected, clinicians should enquire about recent biotin consumption. It may be helpful to provide guidance to patients and ask them to avoid taking certain medications or supplements before blood tests. Lastly, many biomarker and/or disease algorithms involve serial testing, which may help to reduce the impact of interference with a single result.Future perspectiveThe use of high-dose biotin in cosmetic supplements and multiple sclerosis treatments has raised concerns regarding the risk of assay interference. However, recent research suggests the risk of clinically relevant misclassification due to biotin interference may be low. Crucially, this issue reiterates that laboratory results should not be considered in isolation. Instead, patient symptoms, clinical examination findings, laboratory results and imaging should be evaluated in concert to gain a holistic clinical picture and avoid misdiagnosis.Open accessThis work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/Financial & competing interests disclosureThe author has served as a member of Scientific Advisory Boards for Eisai, Roche Diagnostics, and Sanofi Genzyme, has received speaker fees from BRAHMS, Roche Diagnostics and Sanofi Genzyme, and received research grants from Roche Diagnostics. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Writing assistance was utilized in the production of this manuscript. Third-party medical writing assistance, under the direction of the author, was provided by Thomas Burton, BMBS (Gardiner-Caldwell Communications, Macclesfield, UK), and was funded by Roche Diagnostics International Ltd, Rotkreuz, Switzerland.References1. 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Chem. 48(11), 1871–1872 (2002).Crossref, Google ScholarFiguresReferencesRelatedDetailsCited BySelective quantification of the 22-kDa isoform of human growth hormone 1 in serum and plasma by immunocapture and LC–MS/MS15 July 2022 | Analytical and Bioanalytical Chemistry, Vol. 414, No. 20Serum Biotin Levels in General Korean PopulationLaboratory Medicine Online, Vol. 12, No. 3 Vol. 4, No. 1 Follow us on social media for the latest updates Metrics History Received 31 January 2019 Accepted 1 May 2019 Published online 26 July 2019 Published in print December 2019 Information© 2019 Newlands PressKeywordsbiotinclinical practicelaboratory errorslaboratory testingimmunoassayinterferenceOpen accessThis work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/Financial & competing interests disclosureThe author has served as a member of Scientific Advisory Boards for Eisai, Roche Diagnostics, and Sanofi Genzyme, has received speaker fees from BRAHMS, Roche Diagnostics and Sanofi Genzyme, and received research grants from Roche Diagnostics. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Writing assistance was utilized in the production of this manuscript. Third-party medical writing assistance, under the direction of the author, was provided by Thomas Burton, BMBS (Gardiner-Caldwell Communications, Macclesfield, UK), and was funded by Roche Diagnostics International Ltd, Rotkreuz, Switzerland.PDF download