ReviewBone marrow transplantation2021
The importance of endothelial protection: the emerging role of defibrotide in reversing endothelial injury and its sequelae.
Review in Bone marrow transplantation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- A phase 2 trial of defibrotide for the prevention of chimeric antigen receptor T-cell-associated neurotoxicity syndrome.Blood advances · 2023Trial
- Trial
- Endothelial Injury as a Potential Contributor to Cardiovascular Toxicity in Hematologic Malignancies.Diseases (Basel, Switzerland) · 2026Review
- Sequential Sinusoidal Obstruction Syndrome and TA-TMA After Haploidentical Hematopoietic Stem Cell Transplantation: Diagnostic and Therapeutic Challenges.Journal of clinical medicine · 2026Article
- From Glycocalyx Shedding to Microvascular Collapse in Sepsis: Endothelial Pathophysiology, Organ Dysfunction, and Mechanistic Biomarkers.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Islets co-engineered with thrombomodulin and CD47 achieve sustained survival in allogeneic recipients without chronic immunosuppression.JCI insight · 2026Article
- Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19.Biomolecules · 2025Review
- Platelet aggregation elicits FasL expression and hepatocyte apoptosis in sinusoidal obstruction syndrome.Scientific reports · 2025Article
- Article
- Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review.Frontiers in immunology · 2024Review
- Characterization of the endotheliopathy, innate-immune activation and hemostatic imbalance underlying CAR-T cell toxicities: laboratory tools for an early and differential diagnosis.Journal for immunotherapy of cancer · 2023Article
- Immunotherapy associated central nervous system complications in primary brain tumors.Frontiers in oncology · 2023Review
- Role of endothelial cells in graft-versus-host disease.Frontiers in immunology · 2022Review
- A Comparative Study of Porcine and Ovine Derived Defibrotide: Coagulation Profiles, Molecular Characteristics, and DNA Content.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), a potentially life-threatening complication of hematopoietic cell transplantation (HCT), results from prolonged sinusoidal endothelial cell activation and profound endothelial cell damage, with sequelae. Defibrotide, the only drug approved in the United States and Europe for treating VOD/SOS post-HCT, has European Commission orphan drug designation for preventing graft-versus-host disease (GvHD), associated with endothelial dysfunction. This endothelial cell protector and stabilizing agent restores thrombo-fibrinolytic balance and preserves endothelial homeostasis through antithrombotic, fibrinolytic, anti-inflammatory, anti-oxidative, and anti-adhesive activity. Defibrotide also preserves endothelial cell structure by inhibiting heparanase activity. Evidence suggests that downregulating p38 mitogen-activated protein kinase (MAPK) and histone deacetylases (HDACs) is key to defibrotide's endothelial protective effects; phosphatidylinositol 3-kinase/Akt (PI3K/AKT) potentially links defibrotide interaction with the endothelial cell membrane and downstream effects. Despite defibrotide's being most extensively studied in VOD/SOS, emerging preclinical and clinical data support defibrotide for treating or preventing other conditions driven by endothelial cell activation, dysfunction, and/or damage, such as GvHD, transplant-associated thrombotic microangiopathy, or chimeric antigen receptor T-cell (CAR-T) therapy-associated neurotoxicity, underpinned by cytokine release syndrome and endotheliitis. Further preclinical and clinical studies will explore defibrotide's potential utility in a broader range of disorders resulting from endothelial cell activation and dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.