Biotin Interference In Immunoassays Research Articles

Biotin Interference in Immunoassays and Patient Safety.

Biotin Interference in Immunoassays and Patient Safety.

45-Year-Old Woman With Fever and Malaise

45-Year-Old Woman With Fever and Malaise

Interference From High-Dose Biotin Intake in Immunoassays for Potentially Time-Critical Analytes by Roche.

Immunoassays using the interaction between streptavidin and biotin are used for clinical chemical analytes on platforms by many different manufacturers. The design can be susceptible to interference from high-dose biotin intake in patients, which remains an often-overlooked confounder despite recently increased awareness. To evaluate an easily implementable method of in vitro biotin depletion for the removal of biotin interference in immunoassays for potentially time-critical analytes. A biotin stock solution was made and de-identified patient samples were spiked to reach a biotin concentration of 1.126 × 106 pg/mL, the maximum reported biotin concentration 1 to 2 hours after a single oral dose of 300 mg biotin. Then, the resulting interference in Elecsys immunoassays for cortisol, cyclosporine A, tacrolimus, digitoxin, thyroid-stimulating hormone, free triiodothyronine, free thyroxine, C-peptide, insulin, N-terminal pro-B-type natriuretic peptide, troponin T high sensitive, human immunodeficiency virus, procalcitonin, β human chorionic gonadotropin, toxoplasma immunoglobulin M, and toxoplasma immunoglobulin G was evaluated before and after biotin depletion using streptavidin particles. All tested immunoassays, with the exception of toxoplasma immunoglobulin M and toxoplasma immunoglobulin G, suffered from significant biotin interference. The depletion protocol removed assay interference due to biotin and produced results that were close or identical to initial prespike measurements. Despite an increase in turnaround times, biotin adsorption is a feasible countermeasure for biotin interference in Elecsys immunoassays. Until test kits with an increased resistance to the interference from high-dose biotin intake are distributed, the evaluated protocol can provide results properly reflecting the patient's clinical condition.

Understanding and managing biotin interference in immunoassays

Understanding and managing biotin interference in immunoassays

Understanding and managing interferences in clinical laboratory assays: the role of laboratory professionals.

The recently raised concerns regarding biotin interference in immunoassays have increased the awareness of laboratory professionals and clinicians of the evidence that the analytical phase is still vulnerable to errors, particularly as analytical interferences may lead to erroneous results and risks for patient safety. The issue of interference in laboratory testing, which is not new, continues to be a challenge deserving the concern and interest of laboratory professionals and clinicians. Analytical interferences should be subdivided into two types on the basis of the possibility of their detection before the analytical process. The first (type 1) is represented by lipemia, hemolysis and icterus, and the second (type 2), by unusual constituents that are not undetectable before analysis, and may affect the matrix of serum/plasma of individual subjects. Type 2 cannot be identified with current techniques when performing the pre-analytical phase. Therefore, in addition to a more careful evaluation and validation of the method to be used in clinical practice, the awareness of laboratory professionals should be raised as to the importance of evaluating the quality of biological samples before analysis and to adopt algorithms and approaches in the attempt to reduce problems related to erroneous results due to specific or non-specific interferences.

Comprehensive assessment of biotin interference in immunoassays

BackgroundBiotinylated antibodies and analogues are currently used in many immunoassays while biotin is widely used as a dietary supplement. Thus, biotin interference is an emerging issue for clinical laboratories. MethodsVarious concentrations of biotin solutions were prepared using pooled patient serum samples. All analytes were measured by sandwich or competitive immunoassay on the Roche Cobas 8000 e602 platform. ResultsSome of the sandwich immunoassay results were falsely decreased to different extents by different biotin levels, while some of the competitive immunoassay results were falsely increased. The most notable false reductions were in high-sensitivity troponin T, thyroid-stimulating hormone, and follicle-stimulating hormone results, while the most notable false increases were in triiodothyronine and vitamin D results. Other immunoassay results were also affected to some extent by biotin interference. ConclusionsBiotin can interfere in immunoassays and result in aberrant test results. Clinicians should use caution in interpreting abnormal results in patients who ingest biotin.

Biotin Interference in Clinical Immunoassays.

Shifts in consumer behavior and clinical practice have increased reports of biotin interference in immunoassays that incorporate biotin-streptavidin linkages in their design. This rise has significant implications because immunoassays are used to measure a wide range of analytes across medical specialties. The objective of this article was to review the mechanisms of biotin interference, define the scope of affected immunoassays, and summarize strategies for identifying and minimizing biotin interference in clinical samples. The literature was reviewed for reports of biotin interference and sorted by manufacturer. Abstracts from recent scientific meetings and manufacturer-provided data were also reviewed. Immunoassays across a range of different manufacturer platforms are subject to interference by exogenous biotin supplementation. Providers and laboratorians must be aware of this potential interference to avoid patient harm.

Biotin Supplements: A Hair‐Raising Challenge to the Analytical Accuracy of Clinical Immunoassays

Streptavidin(avidin)/ biotin and anti‐biotin/biotin reactions have played a significant role in the development of the field of clinical immunoassay(IA) and are now used in many of the FDA‐cleared IA's that are used for patient care. A marked increase in the use of high‐dose biotin supplements by the general public has led to a steady increase in the incidence of false positive and false negative IA results among subjects that consume biotin at doses of > 1 mg/day. The goals of this study were to investigate the risk of significant biotin interference in IA's that utilize biotinylated reagents and biotin binding proteins and to compare their manufacturer‐established interference thresholds (IFTs) with the serum biotin concentrations that have been observed in single‐dose pharmacokinetic studies of oral biotin therapy in humans.In June of 2016, we reviewed current versions of the manufacturer's “Instructions For Use” (IFUs) for each of the IA methods on 8 of the most widely used automated clinical IA systems. A method was considered to be potentially vulnerable to biotin interference when it utilized a streptavidin/biotin or an anti‐biotin/biotin reaction. Vulnerable methods were further characterized as to the manufacturer‐determined threshold for significant interference by exogenous biotin in a patient sample and whether or not the IFU identified biotin interference as an analytical limitation of the method.We found that 0 to 100 % of the IA's performed on a particular assay system were potentially vulnerable to biotin interference. Depending on the platform, the methods that were at risk for biotin interference were designed to measure a wide variety of analytes including thyroid, steroid and polypeptide hormones, serum proteins, infectious disease serologies, cardiac markers, tumor markers, biomarkers of anemia and autoimmune diseases, and immunosuppressive drugs. The IFTs reported by the manufacturers varied considerably from method to method within a particular assay system and from system to system. For some methods, there was no evidence that an IFT study had been performed (Table 1, n/a). Additional analyses showed that methods with IFTs of <200 nmol/L were likely to be at risk for generating inaccurate test results for samples from subjects whose daily oral biotin intakes are > 1 mg per day. This risk increases as the IFT of the method decreases, increases with the size of a subject's biotin dose, and decreases when specimen collection is delayed 24 to 48 hours after the subject's last oral dose. Until a permanent solution to the problem of biotin interference is offered up by the clinical diagnostics industry or mandated by the FDA, healthcare workers should be aware that biotin supplements can cause falsely increased or decreased results for a wide variety of routine IA's that are used in patient care and should contact the clinical laboratory that performs their testing for up to date information on which of their methods are vulnerable to interference and how to prepare the subject and time the blood draw in order to the minimize the risk of an inaccurate result. Biotin Interference in Immunoassays Performed by Eight Automated Clinical Assay Systems Multi‐Test Assay System Total IA's # Vulnerable to Biotin Interference Biotin Interference Thresholds range (nmol/L) Roche Elecsys® 81 81 21 – 491 Ortho Vitros® 43 29 10 – 82 Siemens Dimens on® 26 21 205 – 2000 (3 r/a) Siemens Centaur® 67 18 10 – 1000 (6 n/a) Beckman Coulter Access®/DXI® 48 14 10 – 1000 (9 n/a) Abbott Architect i2000® 42 2 120 (1 n/a) Siemens Immulite 2000® 64 D ‐‐‐‐‐‐ Diasorin Liaison XL® 42 D ‐‐‐‐‐‐