{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:56:44Z","timestamp":1789012604177,"version":"build-2803163510"},"reference-count":44,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.com.au","clinicalkey.es","clinicalkey.com","journal.chestnet.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["CHEST"],"published-print":{"date-parts":[[2022,8]]},"DOI":"10.1016\/j.chest.2022.03.046","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T05:58:21Z","timestamp":1649483901000},"page":"346-355","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"title":["Defibrotide Therapy for SARS-CoV-2 ARDS"],"prefix":"10.1016","volume":"162","author":[{"given":"David","family":"Frame","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni B.","family":"Scappaticci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Maliarik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Sisson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W.","family":"Pipe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Lawrence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Holinstat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Hyzy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Kaul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin S.","family":"Gregg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vibha N.","family":"Lama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Yanik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"10223","key":"10.1016\/j.chest.2022.03.046_bib2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"issue":"10223","key":"10.1016\/j.chest.2022.03.046_bib3","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0140-6736(20)30211-7","article-title":"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study","volume":"395","author":"Chen","year":"2020","journal-title":"Lancet"},{"issue":"11","key":"10.1016\/j.chest.2022.03.046_bib4","first-page":"400","article-title":"Shared features of endothelial dysfunction between sepsis and its preceding risk factors (aging and chronic disease)","volume":"7","author":"Bermejo-Martin","year":"2018","journal-title":"J\u00a0Clin Med"},{"issue":"32","key":"10.1016\/j.chest.2022.03.046_bib5","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1093\/eurheartj\/ehaa623","article-title":"COVID-19 is, in the end, an endothelial disease","volume":"41","author":"Libby","year":"2020","journal-title":"Eur Heart J"},{"issue":"1","key":"10.1016\/j.chest.2022.03.046_bib6","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41392-020-00454-7","article-title":"Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches","volume":"5","author":"Jin","year":"2020","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.chest.2022.03.046_bib7","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.thromres.2020.04.013","article-title":"Incidence of thrombotic complications in critically ill ICU patients with COVID-19","volume":"191","author":"Klok","year":"2020","journal-title":"Thromb Res"},{"issue":"7","key":"10.1016\/j.chest.2022.03.046_bib8","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1111\/jth.14869","article-title":"High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients","volume":"18","author":"Llitjos","year":"2020","journal-title":"J\u00a0Thrombosis and Hemostas"},{"issue":"4","key":"10.1016\/j.chest.2022.03.046_bib9","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S2213-2600(20)30076-X","article-title":"Pathological findings of COVID-19 associated with acute respiratory distress syndrome 2020","volume":"8","author":"Xu","year":"2020","journal-title":"Lancet Respir Med"},{"issue":"7","key":"10.1016\/j.chest.2022.03.046_bib10","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S2213-2600(20)30243-5","article-title":"Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans","volume":"8","author":"Fox","year":"2020","journal-title":"Lancet Respir Med"},{"key":"10.1016\/j.chest.2022.03.046_bib11","doi-asserted-by":"crossref","unstructured":"The REMAP-CAP, ACTIV-4a, ATTACC Investigators, Ryan Zarychanski. Therapeutic anticoagulation in critically ill patients with Covid-19\u2014preliminary report [published online ahead of print March 12, 2021]. medRxiv. doi: https:\/\/doi.org\/10.1101\/2021.03.10.21252749.","DOI":"10.1101\/2021.03.10.21252749"},{"issue":"4","key":"10.1016\/j.chest.2022.03.046_bib12","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1007\/s11239-020-02105-8","article-title":"Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2","volume":"51","author":"Yin","year":"2021","journal-title":"J\u00a0Thromb Thrombolysis"},{"issue":"4","key":"10.1016\/j.chest.2022.03.046_bib13","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1111\/jth.15267","article-title":"Prolonged elevation of D-dimer levels in convalescent COVID-19 patients is independent of the acute phase response","volume":"19","author":"Townsend","year":"2021","journal-title":"J\u00a0Thromb Haemost"},{"key":"10.1016\/j.chest.2022.03.046_bib14","article-title":"Practical guidance for the prevention of thrombosis and management of coagulopathy and disseminated intravascular coagulation of patients infected with COVID-19","author":"Hunt","year":"2020","journal-title":"Thromb Hemost"},{"issue":"5","key":"10.1016\/j.chest.2022.03.046_bib15","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1111\/jth.14810","article-title":"ISTH interim guidance on recognition and management of coagulopathy in COVID-19","volume":"18","author":"Thachil","year":"2020","journal-title":"J\u00a0Thromb Haemost"},{"issue":"13","key":"10.1016\/j.chest.2022.03.046_bib16","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1182\/blood-2015-10-676924","article-title":"Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure","volume":"127","author":"Richardson","year":"2016","journal-title":"Blood"},{"key":"10.1016\/j.chest.2022.03.046_bib17","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1089\/oli.2006.16.105","article-title":"Defibrotide, a polydisperse mixture of single-stranded phosphodiester oligonucleotides with lifesaving activity in severe hepatic veno-occlusive disease: clinical outcomes and potential mechanisms of action","volume":"16","author":"Kornblum","year":"2006","journal-title":"Oligonucleotides"},{"issue":"12","key":"10.1016\/j.chest.2022.03.046_bib18","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1182\/bloodadvances.2017008375","article-title":"The use of defibrotide in blood and marrow transplantation","volume":"2","author":"Richardson","year":"2018","journal-title":"Blood Adv"},{"key":"10.1016\/j.chest.2022.03.046_bib19","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1586\/ehm.09.30","article-title":"Use of defibrotide in the treatment and prevention of veno-occlusive disease","volume":"2","author":"Richardson","year":"2009","journal-title":"Expert Rev Hematol"},{"key":"10.1016\/j.chest.2022.03.046_bib20","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0014-2999(93)90864-E","article-title":"Defibrotide, a single-stranded polydeoxyribonucleotide acting as an adenosine receptor agonist","volume":"238","author":"Bianchi","year":"1993","journal-title":"Eur J Pharmacol"},{"issue":"4","key":"10.1016\/j.chest.2022.03.046_bib21","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.bbmt.2010.11.019","article-title":"Defibrotide prevents the activation of macrovascular and microvascular endothelia caused by soluble factors released to blood by autologous hematopoietic stem cell transplantation","volume":"17","author":"Palomo","year":"2011","journal-title":"Biol Blood Marrow Transplant"},{"issue":"6","key":"10.1016\/j.chest.2022.03.046_bib22","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1080\/14728222.2021.1944101","article-title":"Defibrotide: potential for treating endothelial dysfunction related to viral and post-infectious syndromes","volume":"25","author":"Richardson","year":"2021","journal-title":"Expert Opin Ther Targets"},{"issue":"8","key":"10.1016\/j.chest.2022.03.046_bib23","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1097\/MBC.0b013e32832da1e3","article-title":"The fibrinolytic mechanism of defibrotide: effect of defibrotide on plasmin activity","volume":"20","author":"Echart","year":"2009","journal-title":"Blood Coag Fibrinolysis"},{"issue":"1","key":"10.1016\/j.chest.2022.03.046_bib24","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/bjh.17240","article-title":"COVID-19-induced endotheliitis: emerging evidence and possible therapeutic strategies","volume":"193","author":"Calabretta","year":"2021","journal-title":"Br J Haematol"},{"issue":"13","key":"10.1016\/j.chest.2022.03.046_bib25","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1182\/blood-2015-10-676114","article-title":"What is going on between defibrotide and endothelial cells? Snapshots reveal the hot spots of their romance","volume":"127","author":"Palomo","year":"2016","journal-title":"Blood"},{"issue":"4","key":"10.1016\/j.chest.2022.03.046_bib27","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/j.1538-7836.2005.01204.x","volume":"3","author":"Schulman","year":"2005","journal-title":"J\u00a0Thromb Haemost"},{"issue":"4","key":"10.1016\/j.chest.2022.03.046_bib28","first-page":"354","article-title":"Clinical features of 141 fatal cases of coronavirus disease in Jinyintan Hospital in Wuhan, China","volume":"44","author":"Xiao","year":"2021","journal-title":"Zhonghua Jie He He Hu Xi Za Zhi"},{"key":"10.1016\/j.chest.2022.03.046_bib29","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s00134-020-06294-x","article-title":"Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study","volume":"47","year":"2021","journal-title":"Intensive Care Medicine"},{"issue":"16","key":"10.1016\/j.chest.2022.03.046_bib30","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1001\/jama.2020.5394","article-title":"Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy","volume":"323","author":"Grasselli","year":"2020","journal-title":"JAMA"},{"issue":"10239","key":"10.1016\/j.chest.2022.03.046_bib31","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1016\/S0140-6736(20)31189-2","article-title":"Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study","volume":"395","author":"Cummings","year":"2020","journal-title":"Lancet"},{"issue":"6","key":"10.1016\/j.chest.2022.03.046_bib32","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/j.mayocp.2020.04.006","article-title":"Association between hypoxemia and mortality in patients with COVID-19","volume":"95","author":"Xie","year":"2020","journal-title":"Mayo Clin Proc"},{"issue":"13","key":"10.1016\/j.chest.2022.03.046_bib33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1001\/jama.2020.17021","article-title":"Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19. The CoDex Randomized Clinical Trial","volume":"324","author":"Tomazini","year":"2020","journal-title":"JAMA"},{"issue":"3","key":"10.1016\/j.chest.2022.03.046_bib34","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1002\/jha2.198","article-title":"Endothelial dysfunction and its critical role in COVID-19-associated coagulopathy: defibrotide as an endothelium-protective, targeted therapy","volume":"2","author":"Garc\u00eda-Bernal","year":"2021","journal-title":"EJHaem"},{"key":"10.1016\/j.chest.2022.03.046_bib35","series-title":"Proceedings of the American Society of Hematology; December 11-14","article-title":"Use of defibrotide in patients with COVID-19 pneumonia: results of the Defi-VID19 phase 2 trial","author":"Ruggeri","year":"2021"},{"issue":"10","key":"10.1016\/j.chest.2022.03.046_bib36","first-page":"1507","article-title":"A\u00a0multicenter study of defibrotide in the prevention of deep venous thrombosis","volume":"44","author":"Gerosa","year":"1989","journal-title":"Minerva Chir"},{"issue":"11","key":"10.1016\/j.chest.2022.03.046_bib37","first-page":"745","article-title":"Prevention of deep venous thrombosis with defibrotide in chest surgery. Controlled multicenter study versus heparin","volume":"78","author":"Rizzi","year":"1987","journal-title":"Minerva Med"},{"issue":"7","key":"10.1016\/j.chest.2022.03.046_bib38","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.bbmt.2016.04.011","article-title":"Defibrotide for treatment of severe veno-occlusive disease in pediatrics and adults: an exploratory analysis using data from the center for international blood and marrow transplant research","volume":"22","author":"Strouse","year":"2016","journal-title":"Biol Blood Marrow Transplant"},{"issue":"6","key":"10.1016\/j.chest.2022.03.046_bib39","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.3390\/cells9061383","article-title":"Neutrophils and neutrophil extra-cellular traps drive necroinflammation in COVID-19","volume":"9","author":"Tomar","year":"2020","journal-title":"Cells"},{"issue":"12","key":"10.1016\/j.chest.2022.03.046_bib40","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1042\/CS20200531","article-title":"SARS-CoV2 may evade innate immune response, causing uncontrolled neutrophil extracellular traps formation and multi-organ failure","volume":"134","author":"Thierry","year":"2020","journal-title":"Clin Sci"},{"issue":"11","key":"10.1016\/j.chest.2022.03.046_bib41","article-title":"Neutrophil extracellular traps in COVID-19","volume":"5","author":"Zou","year":"2020","journal-title":"CI Insight"},{"issue":"6","key":"10.1016\/j.chest.2022.03.046_bib42","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20200652","article-title":"Targeting potential drivers of COVID-19: neutrophil extracellular traps","volume":"217","author":"Barnes","year":"2020","journal-title":"J\u00a0Exp Med"},{"key":"10.1016\/j.chest.2022.03.046_bib43","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.imlet.2020.09.005","article-title":"How NETosis could drive \u201cpost-COVID-19 syndrome\u201d among survivors","volume":"228","author":"Sawadogo","year":"2020","journal-title":"Immunol Lett"},{"issue":"4","key":"10.1016\/j.chest.2022.03.046_bib44","doi-asserted-by":"crossref","first-page":"915","DOI":"10.3390\/cells9040915","article-title":"Neutrophil extracellular traps (NETs) take the central stage in driving autoimmune responses","volume":"9","author":"Fousert","year":"2020","journal-title":"Cells"},{"issue":"17","key":"10.1016\/j.chest.2022.03.046_bib45","article-title":"Endothelium-protective, histone-neutralizing properties of the polyanionic agent defibrotide","volume":"6","author":"Hui","year":"2021","journal-title":"JCI Insight"},{"issue":"11","key":"10.1016\/j.chest.2022.03.046_bib46","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1111\/jth.15100","article-title":"Defibrotide in the COVID-19 coagulopathy: what is the timing?","volume":"18","author":"Maccio","year":"2020","journal-title":"J\u00a0Thromb Haemost"}],"container-title":["CHEST"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0012369222005931?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0012369222005931?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T01:03:16Z","timestamp":1715130196000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0012369222005931"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["S0012369222005931"],"URL":"https:\/\/doi.org\/10.1016\/j.chest.2022.03.046","relation":{},"ISSN":["0012-3692"],"issn-type":[{"value":"0012-3692","type":"print"}],"subject":[],"published":{"date-parts":[[2022,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Defibrotide Therapy for SARS-CoV-2 ARDS","name":"articletitle","label":"Article Title"},{"value":"CHEST","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.chest.2022.03.046","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}