Clin Chem Lab Med 2019; 57(5): 633–640 IFCC Paper Amy K. Saenger, Allan S. Jaffe, Richard Body, Paul O. Collinson, Peter A. Kavsak, Carolyn S.P. Lam, Guillaume Lefèvre, Tobjørn Omland, Jordi Ordóñez-Llanos, Kari Pulkki and Fred S. Apple* Cardiac troponin and natriuretic peptide analytical interferences from hemolysis and biotin: educational aids from the IFCC Committee on Cardiac Biomarkers (IFCC C-CB) https://doi.org/10.1515/cclm-2018-0905 Cardiac troponin I and T (cTnI, cTnT) and the natriuretic Received August 21, 2018; accepted August 31, 2018; previously peptides (NP; B-type natriuretic peptide, BNP; N Termi- ­published online October 6, 2018 nal-proBNP; NT-proBNP) are the primary cardiac bio- markers utilized in the diagnosis of myocardial injury Abstract: Two interferences recently brought to the fore- and infarction (MI) and heart failure (HF), respectively. front as patient safety issues include hemolysis (hemo- As with any clinical laboratory test, there are exogenous globin) and biotin (vitamin B7). The International and endogenous factors that adversely interfere with the Federation for Clinical Chemistry Committee on Cardiac analytical performance of the cTn and NP assays, poten- Biomarkers (IFCC-CB) obtained input from a majority of tially resulting in inappropriate clinical interpretation cTn and NP assay manufacturers to collate information of the results if the interferences are not identified. Ana- related to high-sensitivity (hs)-cTnI, hs-cTnT, contempo- lytical interferences are particularly concerning when rary, and POC cTn assays, and NP assays interferences dealing with cardiac biomarker assays, which are uti- due to hemolysis and biotin. The information contained lized to make time sensitive critical clinical decisions. in these tables was designed as educational tools to aid Two interferences recently brought to the forefront as laboratory professionals and clinicians in troubleshooting patient safety issues include hemolysis (hemoglobin) cardiac biomarker analytical results that are discordant and biotin (vitamin B7, vitamin H, coenzyme R). The with the clinical situation. International Federation for Clinical Chemistry Com- Keywords: biotin; hemolysis; interferences; natriuretic mittee on Cardiac Biomarkers (IFCC-CB) obtained input peptide; troponin. from a majority of cTn and NP assay manufacturers to *Corresponding author: Fred S. Apple, Hennepin County Medical Peter A. Kavsak: Department of Pathology and Molecular Medicine, Center, Department of Laboratory Medicine and Pathology, 701 Park McMaster University, Hamilton, Ontario, Canada Avenue, Minneapolis, MN 55415, USA; and Department of Laboratory Carolyn S.P. Lam: National Heart Centre and Duke-National Medicine and Pathology, University of Minnesota, Minneapolis, MN, University of Singapore, Singapore, Singapore USA, Phone: +1 612 873-3324, Fax: +1 612 904-4229, Guillaume Lefèvre: Department of Biochemistry and Hormonology, E-mail: apple004@umn.edu Hospital Tenon, Sorbonne Universités GRC-14 BIOSFAST, AP-HP, Amy K. Saenger: Department of Laboratory Medicine and Pathology, Paris, France University of Minnesota, Minneapolis, MN, USA Tobjørn Omland: Division of Medicine, Akershus University Hospital, Allan S. Jaffe: Department of Laboratory Medicine and Lørenskog, Norway; and Center for Heart Failure Research, Institute Pathology and Cardiology, Mayo Clinic, Rochester, MN, USA of Clinical Medicine, University of Oslo, Oslo, Norway Richard Body: Emergency Department, Central Manchester University Jordi Ordóñez-Llanos: Servicio de Bioquímica Clínica, Institut Hospitals NHS Foundation Trust, Manchester Academic Health Science d’Investigacions Biomèdiques Sant Pau, Barcelona, Spain; and Centre, Manchester, UK; Cardiovascular Sciences Research Group, Departamento de Bioquímica y Biología Molecular, Universidad Core Technology Facility, Manchester, UK; and Healthcare Sciences Autònoma de Barcelona, Barcelona, Spain Department, Manchester Metropolitan University, Manchester, UK Kari Pulkki: Department of Clinical Chemistry, University of Turku Paul O. Collinson: Department of Clinical Blood Sciences and and Turku University Hospital, Turku, Finland Cardiology, St George’s University Hospitals NHS Foundation Trust and St George’s University of London, London, UK 634 Saenger et al.: Cardiac troponin and natriuretic peptide interferences from hemolysis and biotin collate information related to high-sensitivity (hs)-cTnI, function [7]. Adequate intake is defined at 0.03 mg/day, hs-cTnT, contemporary, and POC cTn assays (Table 1) [1], although consumption has expanded and retail sales of and NP assays (Table 2) [2] interferences due to hemoly- over-the-counter “mega” doses (2.5–10 mg) of biotin have sis and biotin. The information contained in these tables increased significantly due to marketing efforts claiming was designed as educational tools to aid laboratory pro- healthier and stronger hair, skin and nails. Furthermore, fessionals and clinicians in troubleshooting cardiac bio- individuals are often unaware that the supplements they marker analytical results that are discordant with the are ingesting even contain biotin. There are ongoing ran- clinical situation. domized clinical trials in the US and Europe to evaluate Hemolysis is one of the major causes of pre-analytical biotin doses of 300 mg/day in patients with multiple errors, reportedly accounting for 40%–70% of all speci- sclerosis and other inflammatory diseases, resulting in men rejections [3]. Furthermore, a substantial volume of circulating serum biotin concentrations between 170 and hemolyzed samples occur from specimens collected in the 700 μg/L [8]. Immunoassays comprised of biotin labeled emergency department and from indwelling catheters in antibodies or biotin-streptavidin labeled complexes are many intensive care units [4]. The accuracy of cTn results particularly susceptible to interferences for a wide array is of significant importance because it is heavily relied of clinical tests. upon for making appropriate and rapid patient care deci- Data obtained from manufacturers regarding the sions. If hemolysis thresholds are exceeded, the specimen analytical specificity and interference for the cTn and needs to be recollected, resulting in delays in patient care NP assays/platforms are presented in Tables 1 and 2, and an increased risk of iatrogenic injury, infection, and respectively. Interference thresholds were defined as adverse clinical management in the absence of objective the greatest concentration for either hemoglobin or information. Hemolysis is a known confounder of hs-cTn biotin that did not compromise accuracy of the cTn or and cTn assays, causing false positive or false negative NP analytical results. When this threshold was exceeded results; either situation may hinder interpretation of results were classified as either falsely high or low, single or serial values [5]. Detection of hemolyzed samples allowing laboratory professionals to ascertain the per- occurs either manually (visual, qualitative assessment) or formance of their specific assay/platform in the scenario through automated detection (quantitative or semi-quan- of gross hemolysis or potentially excessive endogenous titative assessment) using indices on the clinical chemistry biotin intake. Manufacturers defined their acceptance platform. The latter approach is supported as a benchmark criteria when evaluating and validating interference of good laboratory practice due to the improved reliability, thresholds. The “End User Assessment of Hemolysis” accuracy and standardized approach to reporting results column in Tables 1 and 2 was designed to aid clinical within a laboratory when using automated mechanisms laboratory personnel performing cardiac biomarker to assess hemolysis. For cTn assays with a low threshold testing. If laboratory personnel must visually assess for for hemolysis (>100 mg/dL, i.e. >1 g/L) the reported rate hemolysis before reporting or releasing cTn results the of incorrectly released results is as high as 76% [6]. Not assay was designated as “Qualitative”. If the instrument all immunoassay platforms or point-of-care devices have automatically assesses for hemolysis to allow erroneous the ability to routinely perform automated hemolysis results to be suppressed and alerting the laboratorian detection, presenting potential patient safety issues for the threshold was exceeded, the assay was designated reporting accurate cTn and NP results due to the subjec- as “Quantitative”. tive nature of visual detection of hemoglobin. Moreover, Biotin interference data in the tables state whether hemolysis will be missed if whole blood is used as the a biotinylated antibody is incorporated and/or if biotin matrix for measurements. is used in the assay configuration; it is notable that Biotin interference is a relatively new challenge those assays with either characteristic are more suscep- to laboratories and highlighted by the Food and Drug tible to interference from endogenous biotin use. If high Administration (FDA) warning statement to clinical labo- dose biotin supplementation is known or suspected due ratories (https://www.fda.gov/Safety/MedWatch/Safe- to results that do not correlate with the patient’s clini- tyInformation/SafetyAlertsforHumanMedicalProducts/ cal condition, one possible mitigation strategy could ucm586641.htm). Investigation of potential interferences involve analysis with another assay that is not suscep- from biotin in immunoassays is similar to methods uti- tible to biotin interference. However, this is not always lized for decades in clinical laboratories to probe analyti- a practical solution and may be problematic due to the cal interferences. Biotin is a water-soluble vitamin with lack of standardization of cTn and NP assays. Other pro- a half-life ranging from 8 to 16 h, depending on renal posed strategies include adsorption of excess biotin Table 1: IFCC Committee on Clinical Applications of Cardiac Biomarkers (C-CB) cardiac troponin assay interference table for hemolysis and biotin designated by manufacturer v072618. Company Assay Platform Hemolysis Biotin Hemolysis Influence of End user hemolysis Acceptance Biotinylated Biotin used Interference Acceptance Highest Influence of limit (no hemolysis assessment criteriab antibody in assay threshold criteriab biotin biotin above interference up above the configuration concentration the threshold to stated value) threshold (+/−) tested (+/−) Abbott High Sensitive ARCHITECT 5.0 g/L ND Qualitative ≤10% No No 290 μg/L ≤10% 290 μg/L ND Diagnostics, Troponin-I (500 mg/dL) Alere (3P25)a High Sensitive Alinity i 5.0 g/L ND Qualitative ≤10% No No 290 μg/L ≤10% 290 μg/L ND Troponin-I (500 mg/dL) (8P13)a Contemporary ARCHITECT 5.0 g/L ND Qualitative ≤10% No No 290 μg/L Undefined 290 μg/L ND Troponin-I (500 mg/dL) (2K41) US Abbott POC cTnI i-STAT 6.0 g/L (−) No No ND ND ND (600 mg/dL) Beckman Access hs-cTnI DxI, Access 4.0 g/L ND Quantitative if – ≤10% at No No ND ND ND NA Coulter 2 (400 mg/dL) using Beckman’s hs-cTnI >11.5 integrated platform ng/L – ≤2.30 ng/L at ≤11.5 ng/L cTnI DxI, Access 5.0 g/L ND Quantitative if – ≤10% at cTnI No No 290 μg/L – ≤10% at cTnI 290 μg/L NA (AccuTnI + 3) 2 (500 mg/dL) using Beckman’s ~0.50 μg/L ~0.50 μg/L integrated platform – ≤0.006 μg/L – ≤0.006 μg/L at ~0.05 μg/L at ~0.05 μg/L – ≤0.02 μg/L ≤ 0.02 μg/L at at ~0.01 μg/L ~0.01 μg/L bioMérieux hs-cTnI VIDAS 4.85 g/L ND Qualitative ±10% Yes Yes 2000 μg/L <10% 2000 μg/L ND (485 mg/dL) ET Healthcare hs-cTnIa Pylon 3d 5.0 g/L (+) Qualitative (serum/ ±10% Yes Yes 200 μg/L ±10% 200,000 μg/L ND (500 mg/dL) plasma); NA (whole blood) Fujirebio hs-cTnI Lumipulse 5.10 g/L ND CLSI EP7-A2 ±10% No No ND NA NA NA (Lumipulse) G1200 and (510 mg/dL) G600II LSI Medience hs-cTnIa PATHFAST 10 g/L (−) Quantitative No No 1500 μg/L ±20% 1500 μg/L ND (1000 mg/dL) (cyanmethemoglobin method) cTnIa PATHFAST 10 g/L (−) Quantitative No No 1500 μg/L ±20% 1500 μg/L ND (1000 mg/dL) (cyanmethemoglobin method) cTnI-II PATHFAST 10 g/L (−) Quantitative No No 1500 μg/L ±20% 1500 μg/L ND (1000 mg/dL) (cyanmethemoglobin method) Ortho-Clinical Troponin I ES ECi/ECiQ, 1.0 g/L (+) Automated/ ≤10% Yes No 2.5 μg/L ≤10% at Saenger et al.: Cardiac troponin and natriuretic peptide interferences from hemolysis and biotin Diagnostics 3600, 5600 (100 mg/dL) Quantitative 0.400 μg/L at cTnI conc. of 0.006 μg/L Quidel cTnI Triage 10 g/L (−) Qualitative ≤10% No No ND NA NA NA 635 (1000 mg/dL) Table 1 (continued) 636 Company Assay Platform Hemolysis Biotin Hemolysis Influence of End user hemolysis Acceptance Biotinylated Biotin used Interference Acceptance Highest Influence of limit (no hemolysis assessment criteriab antibody in assay threshold criteriab biotin biotin above interference up above the configuration concentration the threshold to stated value) threshold (+/−) tested (+/−) cTnI SOBa Triage 5.0 g/L (−) Qualitative ≤10% No No ND NA NA NA (500 mg/dL) cTnI Cardioa Triage 1.0 g/L (−) Qualitative ≤10% No No ND NA NA NA (100 mg/dL) Radiometer, TnIa AQT90 FLEX 10 g/L No interference Qualitative NA Yes (pre- Yes (pre- No ≤10% 3 μg/Lc NAc POC (1000 mg/dL) bound) bound) interference up to 3 μg/Lc Radiometer, TnTa AQT90 FLEX 2.0 g/L No interference Qualitative NA No No No ≤9% 50 μg/Lc NAc POC (200 mg/dL) interference up to 50 μg/Lc Response No information provided No information provided biomedical Roche cTnT-hsa MODULAR 1.0 g/L (−) Serum indices on Recovery Yes Yes (as 21 μg/L Recovery 70 μg/L (−) Diagnostics and TnT Gen 5 E170, cobas (100 mg/dL) pre-analytic module; within ±1.4 conjugated within ±1.4 STAT e411, e601, Qualitative ng/L with a Ab, not as ng/L at <14 e602, e801 conc. <14 free biotin) ng/L; ng/L; Recovery Recovery within ±10% ±10% with a at ≥14 ng/L conc. ≥14 ng/L Roche Roche cobas h 232 2.0 g/L (−) Qualitative Mean bias Yes Yes (as 200 μg/L Mean bias 1200 μg/L (−) Diagnostics CARDIAC POC POC system (200 mg/dL) vs. reference conjugated vs. reference POC Troponin T sample: Ab, not as sample: ≤± 15% at free biotin) ≤± 15% 40–2000 μg/L between 40 and 2000 μg/L Siemens High ADVIA 5 g/L ND Qualitative ±10% Yes Yes 3500 μg/L ±10% 3500 μg/L ND Healthineers Sensitivity Centaur® (500 mg/dL) Troponin I XP/XPT (TNIH)a Systems ±10% ±10% Saenger et al.: Cardiac troponin and natriuretic peptide interferences from hemolysis and biotin High Atellica™ IM 5.0 g/L ND Quantitative Yes Yes 3500 μg/L 3500 μg/L ND Sensitivity Analyzer (500 mg/dL) Troponin I (TNIH)a High Dimension® 4.0 g/L ND Quantitative ±10% Yes Yes 300 μg/L ±10% 1200 μg/L (−) Sensitivity EXL™ (400 mg/dL) Troponin I System (TNIH)a High Dimension 4.0 g/L ND Quantitative ±10% Yes Yes 300 μg/L ±10% 1200 μg/L (−) Sensitivity Vista® (400 mg/dL) Troponin I System (TNIH)a Table 1 (continued) Company Assay Platform Hemolysis Biotin Hemolysis Influence of End user hemolysis Acceptance Biotinylated Biotin used Interference Acceptance Highest Influence of limit (no hemolysis assessment criteriab antibody in assay threshold criteriab biotin biotin above interference up above the configuration concentration the threshold to stated value) threshold (+/−) tested (+/−) TnI-Ultra ADVIA 5.0 g/L ND Qualitative ±10% Yes Yes 10 μg/L ±10% 1500 μg/L (−) Centaur® (500 mg/dL) CP/XP/XPT Systems TnI-Ultra Atellica™ IM 5.0 g/L ND Quantitative ±10% Yes Yes 10 μg/L ±10% 1500 μg/L (−) Analyzer (500 mg/dL) TNI Dimension® 5.0 g/L ND Quantitative ±10% Yes Yes 100 μg/L ±10% 1200 μg/L (−) EXL™ (500 mg/dL) System CTNI Dimension® 10 g/L ND Quantitative ±10% No No ND NA NA NA RXL™ (1000 mg/dL) System CTNI Dimension 5.0 g/L ND Quantitative ±10% Yes Yes 100 μg/L ±10% 1200 μg/L (−) Vista® (500 mg/dL) System Troponin-I IMMULITE® 5.0 g/L ND Qualitative ±10% Yes Yes 1500 μg/L ±10% 1500 μg/L ND 2000/2000 (512 mg/dL) XPi Systems Troponin-I IMMULITE® / 5.7 g/L ND Qualitative ±10% Yes Yes 1500 μg/L ±10% 1500 μg/L ND IMMULITE® (570 mg/dL) 1000 Systems Troponin-I IMMULITE® 5.12 g/L <10% Qualitative ±10% Yes Yes 1500 μg/L ±10% 1500 μg/L ND Turbo (512 mg/dL) System Singulex hs-cTnI Clarity 4.55 g/L (−) Visual/qualitative ±10% Yes Yes 10,000 ±10% 10,000 μg/L (−) (455 mg/dL) μg/L Tosoh ST AIA-PACK AIA Series 4.3 g/L ±10% No No ND NA NA NA cTnI 2nd Gen (AIA-1800, (430 mg/dL) AIA-2000, AIA-600II, AIA-900, AIA-360, etc…) ND, not determined; NA, not applicable. aNot yet cleared by the FDA for clinical use in the US. bAcceptance criteria were those defined in the package insert for determining whether interference was considered significant or not. cUnder further investigation. Saenger et al.: Cardiac troponin and natriuretic peptide interferences from hemolysis and biotin 637 Table 2: IFCC Committee on Clinical Applications of Cardiac Biomarkers (C-CB) natriuretic peptide assay interference table for hemolysis and biotin designated by manufacturer v083018. 638 Company Assay Platform Hemolysis Biotin Hemolysis Influence of Hemolysis Acceptance Biotinylated Biotin used Interference Acceptance Highest biotin Influence limit (no hemolysis assessment criteriab antibody in assay threshold criteriab concentration of biotin interference greater than configuration tested above the up to stated the threshold threshold value) (+/−) Abbott BNP (8K28) ARCHITECT 5.0 g/L ND Qualitative ≤10% No No ND NA ND ND Diagnostics (500 mg/dL) BNP (8P24)a Alinity i 5.0 g/L ND Qualitative ≤10% No No ND NA ND ND (500 mg/dL) Alere NT-proBNP ARCHITECT 10 g/L ND Qualitative ≤10% Yes No 4250 μg/L ≤10% 4250 μg/L ND (2R10)a (1000 mg/dL) Abbott POC BNP i-STAT None NA Visual/ Qualitative No No ND NA Beckman BNP Access 2, 5.0 g/L (−) Qualitative ≤10% Yes (pre- Yes (pre- ND NA NA NA Coulter UniCel DxI (500 mg/dL) bound) bound) bioMérieux NT-proBNP2 VIDAS 5.0 g/L ND Qualitative ±10% No No ND NA NA NA (500 mg/dL) ET BNP* Pylon 3d 10 g/L (+) Qualitative ±15% Yes No 200 μg/L ±10% 200 μg/L ND Healthcare (1000 mg/dL) Fujirebio BNP Lumipulse 0.98 g/L ND CLSI EP7-A2 ±10% No No ND NA NA NA G1200/G600II (98 mg/dL) LSI NT-proBNP PATHFAST 1.4 g/L (−) Cyanmethemoglobin 10% No No 1500 μg/L ±20% 1500 μg/L ND Medience (1400 mg/dL) method Ortho- NT-proBNP ECi/ECiQ, 3.0 g/L (+) Automated/ ≤10% Yes No 20 μg/L ≤10% at ~125 ng/L Clinical 3600, 5600 (300 mg/dL) Quantitative (14.8 pmol/L) Diagnostics at 88.4 ng/L Quidel/Alere BNP Triage 10 g/L (+) Qualitative ≤10% No No ND NA NA NA (1000 mg/dL) BNP SOB Triage 5.0 g/L (+) Qualitative ≤10% No No ND NA NA NA (500 mg/dL) BNP Cardioa Triage 1.0 g/L (+) Qualitative ≤10% No No ND NA NA NA (100 mg/dL) NT-proBNPa Triage 5.0 g/L (−) Qualitative ≤10% No No ND NA NA NA (500 mg/dL) Radiometer, NT-proBNPa AQT90 FLEX 2.0 g/L No Qualitative NA Yes (pre- Yes (pre- NAd NAd NAd NAd POC (200 mg/dL) interference bound) bound) Roche proBNP II and MODULAR 10 g/L (−) Serum indices on Recovery ± 20% Yes Yes (as 35 μg/L Recovery of ±10 35 μg/L ND Diagnostics proBNP II STAT E170, cobas (1000 mg/dL) pre-analytic module; at <100 ng/L; conjugated ng/L of initial value Saenger et al.: Cardiac troponin and natriuretic peptide interferences from hemolysis and biotin e411. e601, Qualitative ±10% at ≥100 Ab, no free ≤100 ng/L and e602, e801 ng/L biotin added) ±10% of initial value >100 ng/L Roche Roche CARDIAC cobas h 232 1.78 g/L (−) Qualitative Mean bias Yes Yes (as 30 μg/L <15% for biotin 30 μg/L ND diagnostics proBNP+ POC system (178 mg/dL) vs. reference conjugated conc. up to 10 μg/L POC sample: Ab, no free mean bias vs. ≤± 34 ng/L biotin added) reference sample: (60–225 ng/L) ≤± 34 ng/L and ≤± 15% (60–225 ng/L (225–9000 NT-proBNP) and ng/L) ≤± 15% (225–9000 ng/L NT-proBNP) Table 2 (continued) Company Assay Platform Hemolysis Biotin Hemolysis Influence of Hemolysis Acceptance Biotinylated Biotin used Interference Acceptance Highest biotin Influence limit (no hemolysis assessment criteriab antibody in assay threshold criteriab concentration of biotin interference greater than configuration tested above the up to stated the threshold threshold value) (+/−) Siemens BNP ADVIA 1.0 g/L ND Qualitative ±10% Yes Yes 250 μg/Lc ±10% 1500 μg/L (−) Healthineers Centaur® CP (100 mg/dL) System BNP ADVIA 1.0 g/L ND Qualitative ±10% Yes Yes 250 μg/Lc ±10% 1500 μg/L (−) Centaur® XP/ (100 mg/dL) XPT Systems BNP Atellica™ IM 1.0 g/L ND Quantitative ±10% Yes Yes 250 μg/Lc ±10% 1500 μg/L (−) Analyzer (100 mg/dL) BNP Dimension 5.0 g/L ND Quantitative ±10% Yes Yes 100 μg/L ±10% 1200 μg/L (−) Vista® System (500 mg/dL) NT-proBNP ADVIA 10 g/L ND Qualitative ±10% Yes Yes 75 μg/L ±10% 1500 μg/L (−) Centaur® CP (1000 mg/dL) System NT-proBNPa ADVIA 10 g/L ND Qualitative ±10% Yes Yes 75 μg/L ±10% 1500 μg/L (−) Centaur® XP/ (1000 mg/dL) XPT Systems NT-proBNP Atellica™ IM 10 g/L ND Quantitative ±10% Yes Yes 75 μg/L ±10% 1500 μg/L (−) Analyzer (1000 mg/dL) NT-proBNP Dimension® 10 g/L ND Quantitative ±10% Yes Yes 250 μg/L ±10% 1200 μg/L (−) EXL™ System (1000 mg/dL) NT-proBNP Dimension® 10 g/L ND Quantitative ±10% No No NA NA NA NA RXL™ System (1000 mg/dL) NT-proBNP Dimension 10 g/L ND Quantitative ±10% Yes Yes 100 μg/L ±10% 1200 μg/L (−) Vista® System (1000 mg/dL) NT-proBNPa IMMULITE® 6.0 g/L ND Qualitative ±10% Yes Yes 1500 μg/L ±10% 1500 μg/L ND 2000/2000 (600 mg/dL) XPi Systems Turbo IMMULITE®/ 6.0 g/L ND Qualitative ±10% Yes Yes 1500 μg/L ±10% 1500 μg/L ND NT-proBNPa IMMULITE® (600 mg/dL) Turbo 1000 Systems Thermo MR-proANPa BRAHMS 10 g/L CLSI EP7-A2 ND ND ND ND Fisher MRproANP (1000 mg/dL) Kryptor Tosoh BNP AIA series No information provided No information provided a b ND, not determined; NA, not applicable. Not yet cleared by the FDA for clinical use in the US. Acceptance criteria were those defined in the package insert for determining whether interference was considered significant or not. cNot in current Instructions for Use (IFU). dUnder further investigation. Saenger et al.: Cardiac troponin and natriuretic peptide interferences from hemolysis and biotin 639 640 Saenger et al.: Cardiac troponin and natriuretic peptide interferences from hemolysis and biotin using streptavidin-coated microparticles [8, 9], although References this requires additional validation within the laboratory before implementation. 1. IFCC C-CB. Cardiac Troponin Assay Interference Table Desig- Cardiac biomarker assays, like a majority of clini- nated by Manufacturer: Hemolysis and Biotin. http://www.ifcc. cal laboratory assays, are susceptible to endogenous org/media/477402/ifcc-cardiac-troponin-interference-table- and exogenous interferences to some extent, which may v072618.pdf. Accessed: 21 Aug 2018. 2. 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Plasma levels of biotin metabolites are elevated in hemodialysis patients with cramps. Tohoku J Exp Med 2016;239:263–7. 8. Piketty M, Prie D, Sedel F, Bernard D, Hercend C, Chanson P, Author contributions: All the authors have accepted et al. High-dose biotin therapy leading to false biochemical responsibility for the entire content of this submitted endocrine profiles: validation of a simple method to overcome manuscript and approved submission. biotin interference. Clin Chem Lab Med 2017;55:817–25. Research funding: None declared. 9. Trambas C, Lu ZX, Yen T, Sikaris K. Depletion of biotin using Employment or leadership: None declared. streptavidin coated magnetic beads: a validated solution to the Honorarium: None declared. problem of biotin interference in streptavidin-based methods. Ann Clin Biochem 2018;55:216–26. Competing interests: The funding organization(s) played 10. Trambas C, Lu Z, Yen T, Sikaris K. Characterization of the scope no role in the study design; in the collection, analysis, and and magnitude of biotin interference in susceptible Roche Elec- interpretation of data; in the writing of the report; or in the sys competitive and sandwich immunoassays. Ann Clin Biochem decision to submit the report for publication. 2018;55:205–15.