Abstract
Objectives Biotin >20.0ng/mL (81.8nmol/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. Methods Biotin 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 >20.0ng/mL (81.8nmol/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. Results ACS cohort: 1/797 (0.13%) 0-h and 1/646 (0.15%) 3-h samples had biotin >20.0ng/mL (81.8nmol/L); 99th percentile biotin was 2.62ng/mL (10.7nmol/L; 0-h) and 2.38ng/mL (9.74nmol/L; 3-h). Using conservative assumptions, the likelihood of false-negative AMI prediction due to biotin interference was 0.026% (0-h result; 19ng/L TnT Gen 5 assay cutoff). US laboratory cohort: 15/2023 (0.74%) samples had biotin >20.0ng/mL (81.8nmol/L); 99th percentile biotin was 16.6ng/mL (68.0nmol/L). Misclassification risk due to biotin interference (19ng/L TnT Gen 5 assay cutoff) was 0.025% (0-h), 0.0064% (1-h), 0.00048% (3-h), and <0.00001% (6-h). Conclusions Biotin interference has minimal impact on the TnT Gen 5 assay's clinical utility, and the likelihood of false-negative AMI prediction is extremely low.
Highlights
Biotin is a water-soluble vitamin with an adult recommended adequate intake of 30 μg per day [1]
acute myocardial infarction (AMI) misclassification risk due to biotin interference with the TnT Gen 5 assay was modeled using different assay cutoffs and test timepoints
We aimed to determine the prevalence of elevated biotin concentrations and the associated patient misclassification risk due to biotin interference with the TnT Gen 5 assay in the US intended-use population
Summary
Biotin is a water-soluble vitamin with an adult recommended adequate intake of 30 μg per day [1]. Biotin– streptavidin coupling has been used for decades by manufacturers of in-vitro diagnostic (IVD) devices to immobilize biotinylated proteins [2, 3]; these immunoassays are susceptible to interference from excessive blood biotin concentrations. The biotin-streptavidin-based 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) assay provides a high negative predictive value (NPV; ≥99%) for ruling out acute myocardial infarction (AMI) [4,5,6,7,8]. Biotin concentrations >20.0 ng/mL (81.8 nmol/L) can reduce TnT Gen 5 assay recovery [9], which may lead to lower reported cardiac troponin T (cTnT) concentrations, and false-negative AMI prediction. Immunoassay interference from biotin was considered extremely rare, as interference thresholds are considerably higher than blood
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