Clinical risk assessment of biotin interference with a high-sensitivity cardiac troponin T assay

Abstract

ObjectivesBiotin >20.0 ng/mL (81.8 nmol/L) can reduce Elecsys® Troponin T Gen 5 (TnT Gen 5; Roche Diagnostics) assay recovery, potentially leading to false-negative results in patients with suspected acute myocardial infarction (AMI). We aimed to determine the prevalence of elevated biotin and AMI misclassification risk from biotin interference with the TnT Gen 5 assay.MethodsBiotin was measured using an Elecsys assay in two cohorts: (i) 797 0-h and 646 3-h samples from 850 US emergency department patients with suspected acute coronary syndrome (ACS); (ii) 2023 random samples from a US laboratory network, in which biotin distributions were extrapolated for higher values using pharmacokinetic modeling. Biotin >20.0 ng/mL (81.8 nmol/L) prevalence and biotin 99th percentile values were calculated. AMI misclassification risk due to biotin interference with the TnT Gen 5 assay was modeled using different assay cutoffs and test timepoints.ResultsACS cohort: 1/797 (0.13%) 0-h and 1/646 (0.15%) 3-h samples had biotin >20.0 ng/mL (81.8 nmol/L); 99th percentile biotin was 2.62 ng/mL (10.7 nmol/L; 0-h) and 2.38 ng/mL (9.74 nmol/L; 3-h). Using conservative assumptions, the likelihood of false-negative AMI prediction due to biotin interference was 0.026% (0-h result; 19 ng/L TnT Gen 5 assay cutoff). US laboratory cohort: 15/2023 (0.74%) samples had biotin >20.0 ng/mL (81.8 nmol/L); 99th percentile biotin was 16.6 ng/mL (68.0 nmol/L). Misclassification risk due to biotin interference (19 ng/L TnT Gen 5 assay cutoff) was 0.025% (0-h), 0.0064% (1-h), 0.00048% (3-h), and <0.00001% (6-h).ConclusionsBiotin interference has minimal impact on the TnT Gen 5 assay’s clinical utility, and the likelihood of false-negative AMI prediction is extremely low.

Determination of biotin interference in pediatric obesity related ELISA research kits

“…False negative results in troponin T tests are vital for patients, and newer cardiac troponin T test formulations are now being sought to have a much higher biotin interference threshold [28]. In a study of acute myocardial infarction patients, the probability of biotin interaction giving false negative results to the Elecsys Troponin T Gen 5 (TnT Gen 5; marketed outside the United States [US] as Elecsys Troponin T-high sensitive; Roche Diagnostics International Ltd., Rotkreuz, Switzerland) test was found to be very low [29]. Dilution and biotin removal procedures could be used to reduce biotin interference in immunoassays [30].…”

“…Although it varies according to the type of immunological test used in automated systems, it has been reported that it is possible to use a dose of 10 ng/ml in blood as the lowest threshold value for biotin interference [25,37]. For all the ELISA parameters, biotin % bias values between the groups formed by the addition of biotin at concentrations of 10, 50, 500, and 1000 ng/ml were calculated [4,29,31]. In our study, there was biotin interference in all ELISA parameters commonly used in investigations performed in the eld of pediatric obesity, and this interference was found to be greater in the healthy group.…”

Multimarkers approach in chest pain management in Emergency department: a focus on the prognostic role of sST2 and suPAR

“…High-dose biotin could also be used by patients with metabolic disorders. 12,19,20 hs-cTn may be susceptible to interfere from heterophile antibodies,8-20 hemolysis, biological variation of cardiac troponin T, cardiac troponin autoantibodies, rheumatoid factor, lipemia, and hyperbilirubinemia. 12 Lastly, elevated values could be found in some patients with skeletal muscle disease.…”