{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T16:09:00Z","timestamp":1789834140890,"version":"4.0.1"},"reference-count":170,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["COV20\/00399"],"award-info":[{"award-number":["COV20\/00399"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["2021-SGR-01118"],"award-info":[{"award-number":["2021-SGR-01118"]}]},{"name":"Departament de Recerca i Universitats de la Generalitat de Catalunya","award":["COV20\/00399"],"award-info":[{"award-number":["COV20\/00399"]}]},{"name":"Departament de Recerca i Universitats de la Generalitat de Catalunya","award":["2021-SGR-01118"],"award-info":[{"award-number":["2021-SGR-01118"]}]},{"name":"Dana-Farber Cancer Institute","award":["COV20\/00399"],"award-info":[{"award-number":["COV20\/00399"]}]},{"name":"Dana-Farber Cancer Institute","award":["2021-SGR-01118"],"award-info":[{"award-number":["2021-SGR-01118"]}]},{"name":"RJ Corman Multiple Myeloma Research Fund","award":["COV20\/00399"],"award-info":[{"award-number":["COV20\/00399"]}]},{"name":"RJ Corman Multiple Myeloma Research Fund","award":["2021-SGR-01118"],"award-info":[{"award-number":["2021-SGR-01118"]}]},{"name":"Paula and Rodger Riney Multiple Myeloma Research Fund","award":["COV20\/00399"],"award-info":[{"award-number":["COV20\/00399"]}]},{"name":"Paula and Rodger Riney Multiple Myeloma Research Fund","award":["2021-SGR-01118"],"award-info":[{"award-number":["2021-SGR-01118"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Defibrotide, which is approved for treating hepatic veno-occlusive disease (VOD)\/sinusoidal obstruction syndrome (SOS), exhibits pleiotropic anti-inflammatory, anti-thrombotic, and fibrinolytic properties, conferring broad endothelial protective effects. Given these mechanisms, defibrotide has potential utility in various conditions involving endothelial injury or activation. In this review we outline the endothelial-protective mechanisms of defibrotide and comprehensively summarize current evidence supporting its applications in hematologic malignancies, including the prevention and treatment of hepatic VOD\/SOS, graft-versus-host disease, and transplant-associated thrombotic microangiopathy. Additionally, we discuss its role in mitigating key toxicities linked to chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We also explore emerging evidence on defibrotide\u2019s potential in SARS-CoV-2 infection-associated endotheliopathies, including acute COVID-19 and post-acute sequelae of SARS-CoV-2 infection (\u201clong-COVID\u201d), and the endothelial protective activity of defibrotide in these settings. Finally, we highlight potential future applications of defibrotide in hematologic malignancies and viral infections, emphasizing its multimodal mechanism of action.<\/jats:p>","DOI":"10.3390\/biom15071004","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T07:54:23Z","timestamp":1752479663000},"page":"1004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4997-9999","authenticated-orcid":false,"given":"Edward","family":"Richardson","sequence":"first","affiliation":[{"name":"Department of Medicine, Warren Alpert Medical School at Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifton C.","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8105-1322","authenticated-orcid":false,"given":"Eleonora","family":"Calabretta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, 20089 Milan, Italy"},{"name":"IRCCS Humanitas Research Hospital, 20089 Milan, Italy"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2272-7908","authenticated-orcid":false,"given":"Francesco","family":"Corrado","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA 02215, USA"},{"name":"Department of Biomedical Sciences, Humanitas University, 20089 Milan, Italy"},{"name":"IRCCS Humanitas Research Hospital, 20089 Milan, Italy"},{"name":"Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9888-5737","authenticated-orcid":false,"given":"Mehmet H.","family":"Kocoglu","sequence":"additional","affiliation":[{"name":"University of Maryland Greenebaum Comprehensive Cancer Center, Department of Medicine, University of Maryland School of Medicine,  Baltimore, MD 21201, USA"},{"name":"Transplant and Cellular Therapy Program, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca M.","family":"Baron","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Marie","family":"Connors","sequence":"additional","affiliation":[{"name":"Division of Hematology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Iacobelli","sequence":"additional","affiliation":[{"name":"Techitra S.r.l., 20123 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee-Jen","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J.","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0043-3562","authenticated-orcid":false,"given":"Aaron P.","family":"Rapoport","sequence":"additional","affiliation":[{"name":"University of Maryland Greenebaum Comprehensive Cancer Center, Department of Medicine, University of Maryland School of Medicine,  Baltimore, MD 21201, USA"},{"name":"Transplant and Cellular Therapy Program, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maribel","family":"D\u00edaz-Ricart","sequence":"additional","affiliation":[{"name":"Hematopathology, Pathology Department, CDB, Hospital Clinic,  IDIBAPS, 08036 Barcelona, Spain"},{"name":"Barcelona Endothelium Team, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Jos\u00e9","family":"Mart\u00ednez-Mellado","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital Virgen de la Arrixaca, IMIB-Pascual Parrilla, University of Murcia, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3144-0124","authenticated-orcid":false,"given":"Carmelo","family":"Carlo-Stella","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, 20089 Milan, Italy"},{"name":"IRCCS Humanitas Research Hospital, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9080-1466","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Moraleda","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Institute of Biomedical Research (IMIB-Pascual Parrilla), University of Murcia, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"ref_1","unstructured":"Jazz Pharmaceuticals Inc. 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