{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:39:40Z","timestamp":1792715980893,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vox Sanguinis"],"abstract":"Abstract<\/jats:title>\n \n Background and Objectives<\/jats:title>\n \n Growth of gram\u2010negative bacteria in a platelet concentrate (PC) is inevitably accompanied by the accumulation of endotoxin, which is the major component of the outer cell membrane of these organisms. However, less is known about the kinetics of endotoxin accumulation in PC and its biological activity. Therefore, the endotoxin level of\n Klebsiella pneumoniae<\/jats:italic>\n contaminated PCs was measured over time. In addition, the biological activity of the contaminants was analysed by an assay that mimics the human fever response in vitro.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n \n The bacterial endotoxin test and the monocyte activation test were established for PC samples for endotoxin and pyrogen detection, respectively. Low\u2010count spiking of PCs using\n K. pneumoniae<\/jats:italic>\n PEI\u2010B\u2010P\u201008 was performed by six laboratories, and samples were taken over time. The samples were analysed for the number of viable cells, the amount of endotoxin and their capacity to induce the production of fever\u2010inducing cytokine interleukin 6 (IL\u20106).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n K. pneumoniae<\/jats:italic>\n showed fast proliferation in contaminated PCs reaching stationary phase 36\u2009h post\u2010spiking. Endotoxin was measurable in samples with a bacterial load of more than 10\n 3<\/jats:sup>\n \u2009CFU\/mL and increased proportionally to the number of bacteria present. IL\u20106 production was found to be linked to endotoxin levels in PCs reaching levels of high pyrogenicity 24\u2009h post\u2010spiking.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n PCs contaminated with more than 10\n 3<\/jats:sup>\n \u2009CFU\/mL of\n K. pneumoniae<\/jats:italic>\n might be a risk for patients due to their ability to induce pyrogenic reactions during transfusion.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/vox.70388","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:06:18Z","timestamp":1792713978000},"source":"Crossref","is-referenced-by-count":0,"title":["From contamination to fever: The role of endotoxin levels in bacterially contaminated platelet concentrates"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0974-2265","authenticated-orcid":false,"given":"Marcel","family":"Prax","sequence":"first","affiliation":[{"name":"Section Microbiological Safety, Department of Infectious Diseases Paul\u2010Ehrlich\u2010Institut Langen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3164-2035","authenticated-orcid":false,"given":"Lea","family":"Debes","sequence":"additional","affiliation":[{"name":"Section Microbiological Safety, Department of Infectious Diseases Paul\u2010Ehrlich\u2010Institut Langen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4143-5753","authenticated-orcid":false,"given":"Paul","family":"Adomeit","sequence":"additional","affiliation":[{"name":"Section Microbiological Safety, Department of Infectious Diseases Paul\u2010Ehrlich\u2010Institut Langen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9637-8937","authenticated-orcid":false,"given":"Michel\u2010Andr\u00e9s","family":"Garc\u00eda\u2010Ot\u00e1lora","sequence":"additional","affiliation":[{"name":"School of Medicine and Health Science, Public Health Research Group Universidad del Rosario Bogot\u00e1 Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3230-3287","authenticated-orcid":false,"given":"Carl P.","family":"McDonald","sequence":"additional","affiliation":[{"name":"National Health Service Blood and Transplant London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0598-8754","authenticated-orcid":false,"given":"Marc","family":"Cloutier","sequence":"additional","affiliation":[{"name":"Hema\u2010Qu\u00e9bec Qu\u00e9bec Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Gravemann","sequence":"additional","affiliation":[{"name":"German Red Cross Blood Service NSTOB Springe Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4370-5724","authenticated-orcid":false,"given":"Opeyemi","family":"Adesina","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science Babcock University Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-5432","authenticated-orcid":false,"given":"Morenike","family":"Adeoye\u2010Isijola","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science Babcock University Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Hubloher","sequence":"additional","affiliation":[{"name":"Section Microbiological Safety, Department of Infectious Diseases Paul\u2010Ehrlich\u2010Institut Langen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hellen","family":"Sarela","sequence":"additional","affiliation":[{"name":"Constantia Kloof, South African National Blood Service Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Vollmer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Laboratoriums\u2010 und Transfusionsmedizin, Herz\u2010 und Diabeteszentrum NRW Universit\u00e4tsklinik der Ruhr\u2010Universit\u00e4t Bochum Bad Oeynhausen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2394-4413","authenticated-orcid":false,"given":"Oleg","family":"Krut","sequence":"additional","affiliation":[{"name":"Section Microbiological Safety, Department of Infectious Diseases Paul\u2010Ehrlich\u2010Institut Langen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0705-4987","authenticated-orcid":false,"given":"Sandra","family":"Ramirez\u2010Arcos","sequence":"additional","affiliation":[{"name":"Medical Microbiology Canadian Blood Services Ottawa Ontario Canada"},{"name":"Department of Biochemistry, Microbiology and Immunology University of Ottawa Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"ISBT Transfusion\u2010Transmitted Infectious Diseases Working Party \u201cSubgroup on Bacteria\u201d","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/trf.15780","article-title":"Bacterial contamination and septic transfusion reaction rates associated with platelet components before and after introduction of primary culture: experience at a US Academic Medical Center 1991 through 2017","volume":"60","author":"Kundrapu S","year":"2020","journal-title":"Transfusion"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev.biochem.71.110601.135414","article-title":"Lipopolysaccharide endotoxins","volume":"71","author":"Raetz CRH","year":"2002","journal-title":"Annu Rev Biochem"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25073927","article-title":"Diversity, complexity, and specificity of bacterial lipopolysaccharide (LPS) structures impacting their detection and quantification","volume":"25","author":"Dardelle F","year":"2024","journal-title":"Int J Mol Sci"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"3749","DOI":"10.4049\/jimmunol.162.7.3749","article-title":"Cutting edge: toll\u2010like receptor 4 (TLR4)\u2010deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product","volume":"162","author":"Hoshino K","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.imlet.2018.10.006","article-title":"Pyrogens, a polypeptide produces fever by metabolic changes in hypothalamus: mechanisms and detections","volume":"204","author":"Prajitha N","year":"2018","journal-title":"Immunol Lett"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1182\/blood-2005-06-2202","article-title":"Platelet Toll\u2010like receptor expression modulates lipopolysaccharide\u2010induced thrombocytopenia and tumor necrosis factor\u2010alpha production in vivo","volume":"107","author":"Aslam R","year":"2006","journal-title":"Blood"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.ejcb.2010.10.007","article-title":"The soluble interleukin 6 receptor: generation and role in inflammation and cancer","volume":"90","author":"Chalaris A","year":"2011","journal-title":"Eur J Cell Biol"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jim.2005.01.010","article-title":"International validation of novel pyrogen tests based on human monocytoid cells","volume":"298","author":"Hoffmann S","year":"2005","journal-title":"J Immunol Methods"},{"key":"e_1_2_9_10_1","first-page":"70","article-title":"Die Erfassung von Pyrogenen in einem humanen Vollblutmodell","volume":"12","author":"Hartung T","year":"1995","journal-title":"ALTEX"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000536242","article-title":"Growth and distribution of bacteria in contaminated whole blood and derived blood components","volume":"51","author":"Gravemann U","year":"2024","journal-title":"Transfus Med Hemother"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1111\/vox.12548","article-title":"Enlargement of the WHO international repository for platelet transfusion\u2010relevant bacteria reference strains","volume":"112","author":"Spindler\u2010Raffel E","year":"2017","journal-title":"Vox Sang"},{"key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1111\/trf.17497","article-title":"Meta\u2010analysis of bacterial growth characteristics in platelet components: refining the inputs of a simulation analysis comparing the relative safety of testing strategies","volume":"63","author":"Walker BS","year":"2023","journal-title":"Transfusion"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1111\/vox.13654","article-title":"Characterization of transfusion\u2010relevant bacteria reference strains in a lyophilized format","volume":"119","author":"Prax M","year":"2024","journal-title":"Vox Sang"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/vox.12427","article-title":"Bacterial survival and distribution during buffy coat platelet production","volume":"111","author":"Taha M","year":"2016","journal-title":"Vox Sang"},{"key":"e_1_2_9_16_1","first-page":"73","article-title":"Collaborative study for the establishment of the WHO 3(rd) International Standard for Endotoxin, the Ph. Eur. endotoxin biological reference preparation batch 5 and the USP Reference Standard for Endotoxin Lot H0K354","volume":"2015","author":"Findlay L","year":"2015","journal-title":"Pharmeur Bio Sci Notes"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/ijc.2910410324","article-title":"Establishment of a human cell line (Mono Mac 6) with characteristics of mature monocytes","volume":"41","author":"Ziegler\u2010Heitbrock HW","year":"1988","journal-title":"Int J Cancer"},{"key":"e_1_2_9_18_1","unstructured":"ICCVAM.ICCVAM\u2010recommended test method protocol: the monocytoid cell line Mono Mac 6\/interleukin\u20106 in vitro pyrogen test (NIH publication 08\u20106392). 2008. Available from:https:\/\/ntp.niehs.nih.gov\/sites\/default\/files\/iccvam\/docs\/protocols\/pyro\u2010mm6il6.pdf. Last accessed 1 Aug 2025."},{"key":"e_1_2_9_19_1","unstructured":"FarzamK NesselTA QuickJ.Erythromycin. 2025. Available from:https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK532249\/. Last accessed 9 Oct 2026."},{"key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"4192","DOI":"10.1038\/s41598-021-83487-4","article-title":"An in vitro study on factors affecting endotoxin neutralization in human plasma using the limulus amebocyte lysate test","volume":"11","author":"Harm S","year":"2021","journal-title":"Sci Rep"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1128\/CMR.8.2.268","article-title":"Endotoxemia: methods of detection and clinical correlates","volume":"8","author":"Hurley JC","year":"1995","journal-title":"Clin Microbiol Rev"},{"key":"e_1_2_9_22_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.biologicals.2024.101808","article-title":"The impact of LPS mutants on endotoxin masking in different detection systems","volume":"89","author":"Burgmaier L","year":"2025","journal-title":"Biologicals"},{"key":"e_1_2_9_23_1","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/3136493","article-title":"A fatal case of septic shock secondary to Acinetobacter bacteremia acquired from a platelet transfusion","volume":"2019","author":"Nevala\u2010Plagemann C","year":"2019","journal-title":"Case Rep Med"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1093\/ajcp\/aqx167","article-title":"Quality improvement after multiple fatal transfusion\u2010transmitted bacterial infections","volume":"149","author":"Corean J","year":"2018","journal-title":"Am J Clin Pathol"},{"key":"e_1_2_9_25_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/trf.15617","article-title":"Genotypic study of Citrobacter koseri, an emergent platelet contaminant since 2012 in France","volume":"60","author":"Emery A","year":"2020","journal-title":"Transfusion"},{"key":"e_1_2_9_26_1","first-page":"2524","article-title":"Phase I trial of intravenously administered endotoxin (Salmonella abortus equi) in cancer patients","volume":"51","author":"Engelhardt R","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_9_27_1","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nature01326","article-title":"The immunopathogenesis of sepsis","volume":"420","author":"Cohen J","year":"2002","journal-title":"Nature"},{"key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1056\/NEJM197012102832404","article-title":"Detection of endotoxin in the blood of patients with sepsis due to gram\u2010negative bacteria","volume":"283","author":"Levin J","year":"1970","journal-title":"N Engl J Med"},{"key":"e_1_2_9_29_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1177\/096805199400100407","article-title":"Limulus amebocyte lysate (LAL) detection of endotoxin in human blood","volume":"1","author":"Novitsky TJ","year":"1994","journal-title":"J Endotoxin Res"},{"key":"e_1_2_9_30_1","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1038\/s41598-024-52735-8","article-title":"Heparin enables the reliable detection of endotoxin in human serum samples using the limulus amebocyte lysate assay","volume":"14","author":"Harm S","year":"2024","journal-title":"Sci Rep"},{"key":"e_1_2_9_31_1","doi-asserted-by":"crossref","DOI":"10.1038\/srep44750","article-title":"Biological activity of masked endotoxin","volume":"7","author":"Schwarz H","year":"2017","journal-title":"Sci Rep"},{"key":"e_1_2_9_32_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.transci.2009.07.001","article-title":"Preparation, storage and quality control of platelet concentrates","volume":"41","author":"Tynng\u00e5rd N","year":"2009","journal-title":"Transfus Apher Sci"},{"key":"e_1_2_9_33_1","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms12020258","article-title":"Bacterial contamination of platelet products","volume":"12","author":"Jacobs MR","year":"2024","journal-title":"Microorganisms"},{"key":"e_1_2_9_34_1","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1086\/529143","article-title":"Relationship between bacterial load, species virulence, and transfusion reaction with transfusion of bacterially contaminated platelets","volume":"46","author":"Jacobs MR","year":"2008","journal-title":"Clin Infect Dis"},{"key":"e_1_2_9_35_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/vox.12027","article-title":"Bacterial growth in red blood cell units exposed to uncontrolled temperatures: challenging the 30\u2010minute rule","volume":"105","author":"Ramirez\u2010Arcos S","year":"2013","journal-title":"Vox Sang"},{"key":"e_1_2_9_36_1","article-title":"Outstanding contributions of LAL technology to pharmaceutical and medical science: review of methods, progress, challenges, and future perspectives in early detection and management of bacterial infections and invasive fungal diseases","volume":"9","author":"Tamura H","year":"2021","journal-title":"Biomedicine"}],"container-title":["Vox Sanguinis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/vox.70388","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/vox.70388","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/vox.70388","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:06:23Z","timestamp":1792713983000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/vox.70388"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":35,"alternative-id":["10.1111\/vox.70388"],"URL":"https:\/\/doi.org\/10.1111\/vox.70388","archive":["Portico"],"relation":{},"ISSN":["0042-9007","1423-0410"],"issn-type":[{"value":"0042-9007","type":"print"},{"value":"1423-0410","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"article-number":"vox.70388"}}