{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T04:26:38Z","timestamp":1714451198291},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,7,21]],"date-time":"2015-07-21T00:00:00Z","timestamp":1437436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["201104076"],"award-info":[{"award-number":["201104076"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vox Sanguinis"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Background and Objectives<\/jats:title><jats:p>Six patients died and one patient survived following infusion of a specific lot of intravenous immunoglobulin (<jats:styled-content style=\"fixed-case\">IVIG<\/jats:styled-content>) within half an hour in May 2008. This study elucidated the underlying pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>A variety of protein fractionation and identification approaches were employed to determine the abnormal components in <jats:styled-content style=\"fixed-case\">IVIG<\/jats:styled-content> products obtained from the hospital where the patients were treated. Animal studies using mice and monkeys were conducted to elucidate the pathophysiological mechanisms. In animal experiments, the effect and distribution of immunoglobulin was investigated using <jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content> staining and immunohistochemistry (<jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>) separately, while platelets and fibrinogen depletion were utilized to determine a possible link between thromboembolism formation in animals and the lethal effect of the <jats:styled-content style=\"fixed-case\">IVIG<\/jats:styled-content>. The size and distribution of the protein aggregates were determined with Coulter Counter Multisizer\u20103 after the dilution of the <jats:styled-content style=\"fixed-case\">IVIG<\/jats:styled-content> with plasma, and the lethal effect of the protein aggregates was simulated with artificial microparticles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">IVIG<\/jats:styled-content> retrieved from the hospital was found to have striking similarities to the heat\u2010treated <jats:styled-content style=\"fixed-case\">IVIG<\/jats:styled-content> in terms of protein aggregation profiles and lethal effects. Post\u2010mortem examination indicated that immunoglobulin aggregates were mainly found in the lung of the animals, while depletion of platelets and fibrinogen from the <jats:styled-content style=\"fixed-case\">IVIG<\/jats:styled-content> preparations failed to prevent the death of the animals. Similar amount of artificial microparticles caused animal death in similar fashion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings indicate that the retrieved <jats:styled-content style=\"fixed-case\">IVIG<\/jats:styled-content> exerted its lethal effects by blocking the pulmonary circulation without markedly altering the coagulation cascade or immunological events.<\/jats:p><\/jats:sec>","DOI":"10.1111\/vox.12307","type":"journal-article","created":{"date-parts":[[2015,7,21]],"date-time":"2015-07-21T19:12:53Z","timestamp":1437505973000},"page":"27-35","source":"Crossref","is-referenced-by-count":5,"title":["Acute pulmonary embolism caused by highly aggregated intravenous immunoglobulin"],"prefix":"10.1111","volume":"110","author":[{"given":"C. F.","family":"Yu","sequence":"first","affiliation":[{"name":"National Institutes for Food and Drug Control Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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