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Clot formation might be associated with this complication, but the precise mechanism of an abnormal elevation in pressure has not been identified. We investigated sufficient conditions for in-circuit elevation in pressure using an<jats:italic>ex vivo<\/jats:italic>re-circulation circuit with porcine blood. Specifically, we investigated the effect of blood conditions, the type of anticoagulation, and pro-inflammatory stimulation on in-circuit pressure. We also examined the cause of an abnormal elevation of in-circuit pressure by specifically degrading DNA, RNA, or protein components of an obstructed filter and by using immunofluorescent techniques. Neither a change in temperature nor change in pH in the blood increased in-circuit pressure. In contrast, long-term storage of blood, pro-inflammatory stimulation by phorbol myristate acetate, and heparin administration significantly increased in-circuit pressure. Abnormal in-circuit elevation in pressure was associated with deposition of extracellular DNA on the outlet surface of the filter. Administration of DNase resulted in a rapid decline of in-circuit pressure. In an<jats:italic>ex vivo<\/jats:italic>re-circulation circuit system, extracellular DNA deposition on the filter is responsible for an abnormal in-circuit elevation in pressure. Senescent leukocytes, stimulated leukocytes, and heparin exposure are associated with extracellular DNA deposition.<\/jats:p>","DOI":"10.1038\/s41598-019-57173-5","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T11:03:28Z","timestamp":1579172608000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1118-9262","authenticated-orcid":false,"given":"Nozomi","family":"Yashima","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6204-8400","authenticated-orcid":false,"given":"Takashi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Kajiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyuki","family":"Kakihana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikuro","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,1,16]]},"reference":[{"issue":"1","key":"57173_CR1","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/S1053-0770(05)80053-9","volume":"9","author":"M Blomb\u00e4ck","year":"1995","unstructured":"Blomb\u00e4ck, M. et al. 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