ArticleJournal of thrombosis and haemostasis : JTH2020
Fondaparinux pentasaccharide reduces sepsis coagulopathy and promotes survival in the baboon model of Escherichia coli sepsis.
Article in Journal of thrombosis and haemostasis : JTH, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Immunothrombosis in Sepsis: Cellular Crosstalk, Molecular Triggers, and Therapeutic Opportunities-A Review.International journal of molecular sciences · 2025Review
- A possible role of plasmin-dependent activation of TGF-β in cancer-associated thrombosis: Implications for therapy.Cancer metastasis reviews · 2024Review
- Promising Drug Fondaparinux for the Treatment of COVID-19: an In Silico Analysis of Low Molecular Weight Heparin, Direct Oral Anticoagulant, and Antiplatelet Drug Interactions with Host Protease Furin.Cardiovascular drugs and therapy · 2024Article
- Heparan sulfates and heparan sulfate binding proteins in sepsis.Frontiers in molecular biosciences · 2023Review
- Efficacy and safety of fondaparinux in preventing venous thromboembolism in Chinese cancer patients: a single-arm, multicenter, retrospective study.Frontiers in oncology · 2023Article
- SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock.Frontiers in physiology · 2023Review
- Venous Thromboembolism in Sepsis: From Bench to Bedside.Biomedicines · 2022Review
- Antithrombotic and Anti-Inflammatory Effects of Fondaparinux and Enoxaparin in Hospitalized COVID-19 Patients: The FONDENOXAVID Study.Journal of blood medicine · 2021Article
- The Toll-Like Receptor 2 Ligand Pam2CSK4 Activates Platelet Nuclear Factor-κB and Bruton's Tyrosine Kinase Signaling to Promote Platelet-Endothelial Cell Interactions.Frontiers in immunology · 2021Article
- Large animal models for translational research in acute kidney injury.Renal failure · 2020Review
- The role of endothelial shear stress on haemodynamics, inflammation, coagulation and glycocalyx during sepsis.Journal of cellular and molecular medicine · 2020Review
- COVID-19, coagulopathy and venous thromboembolism: more questions than answers.Internal and emergency medicine · 2020Review
- Fondaparinux: Should It Be Studied in Patients with COVID-19 Disease?TH open : companion journal to thrombosis and haemostasis · 2020Article
- Pulmonary thrombosis in 2019-nCoV pneumonia?Journal of thrombosis and haemostasis : JTH · 2020Article
- Pulmonary embolism in patients with coronavirus disease-2019 (COVID-19) pneumonia: a narrative review.Annals of intensive care · 2020Review
- Animal Models of Type III Secretion System-Mediated Pathogenesis.Pathogens (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundSepsis triggers dysfunction of coagulation and fibrinolytic systems leading to disseminated intravascular coagulation (DIC) that contributes to organ failure and death. Fondaparinux (FPX) is a synthetic pentasaccharide that binds to antithrombin (AT) and selectively inhibits factor (F) Xa and other upstream coagulation proteases but not thrombin (T).
objectivesWe used a baboon model of lethal Escherichia coli sepsis to investigate the effects of FPX treatment on DIC, organ function, and outcome.
methodsTwo experimental groups were studied: (a) E. coli challenge (n = 4); and (b) E coli plus FPX (n = 4). Bacteremia was modeled by intravenous infusion of pathogen (1-2 × 10
resultsBacteremia rapidly increased plasma levels of inhibitory complexes of AT with coagulation proteases. Activation markers of both intrinsic (FXIa-AT), and extrinsic (FVIIa-AT) pathways were significantly reduced in FPX-treated animals. Factor Xa-AT and TAT complexes were maximal at 4 to 8 h post challenge and reduced >50% in FPX-treated animals. Fibrinogen consumption, fibrin generation and degradation, neutrophil and complement activation, and cytokine production were strongly induced by sepsis. All parameters were significantly reduced, while platelet count was unchanged by the treatment. Fondaparinux infusion attenuated organ dysfunction, prolonged survival, and saved two of four challenged animals (log-rank Mantel-Cox test, P = .0067).
conclusionOur data indicate that FPX-mediated inhibition of coagulation prevents sepsis coagulopathy; protects against excessive complement activation, inflammation, and organ dysfunction; and provides survival benefit in E. coli sepsis.
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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 Socratic graph.