ArticleBlood2021
Factor XII plays a pathogenic role in organ failure and death in baboons challenged with Staphylococcus aureus.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Factor XII-A New Therapeutic Target? A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Trial
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Anthrax toxins exacerbate sepsis-induced coagulopathy and endothelial dysfunction in a baboon model of anthrax.Journal of thrombosis and haemostasis : JTH · 2026Article
- Therapeutic Potential of C1-Inhibitor in Vascular Diseases and Beyond.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Capillary leak syndrome in sepsis: the role of intrinsic coagulation pathway activation.BMC infectious diseases · 2025Article
- An antibody targeting high-molecular-weight kininogen blocks contact system activation in a model of polymicrobial sepsis.Journal of thrombosis and haemostasis : JTH · 2025Article
- Bacterial infection and activation of the contact pathway of coagulation.Blood vessels, thrombosis & hemostasis · 2025Review
- Protective effects of factor XI inhibition by abelacimab in a baboon model of live Staphylococcus aureus sepsis.Journal of thrombosis and haemostasis : JTH · 2025Article
- Factor XII-driven coagulation traps bacterial infections.The Journal of experimental medicine · 2025Article
- Article
- The role of programmed cell death in organ dysfunction induced by opportunistic pathogens.Critical care (London, England) · 2025Review
- The physicochemical properties of lipopolysaccharide chemotypes regulate activation of the contact pathway of blood coagulation.The Journal of biological chemistry · 2025Article
- Pathophysiological dynamics in the contact, coagulation, and complement systems during sepsis: Potential targets for nafamostat mesilate.Journal of intensive medicine · 2024Review
- The Interaction of Complement and Intrinsic Coagulation System: A Comparative Study between COVID-19 and Bacterial Sepsis Patients.Journal of clinical medicine · 2024Article
- Activation of coagulation FXI promotes endothelial inflammation and amplifies platelet activation in a nonhuman primate model of hyperlipidemia.Research and practice in thrombosis and haemostasis · 2024Article
- Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.Thrombosis and haemostasis · 2023Article
- Anti-HK antibody inhibits the plasma contact system by blocking prekallikrein and factor XI activation in vivo.Blood advances · 2023Article
- Blocking domain 6 of high molecular weight kininogen to understand intrinsic clotting mechanisms.Research and practice in thrombosis and haemostasis · 2022Article
- Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19.Blood advances · 2022Article
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Activation of coagulation factor (F) XI promotes multiorgan failure in rodent models of sepsis and in a baboon model of lethal systemic inflammation induced by infusion of heat-inactivated Staphylococcus aureus. Here we used the anticoagulant FXII-neutralizing antibody 5C12 to verify the mechanistic role of FXII in this baboon model. Compared with untreated control animals, repeated 5C12 administration before and at 8 and 24 hours after bacterial challenge prevented the dramatic increase in circulating complexes of contact system enzymes FXIIa, FXIa, and kallikrein with antithrombin or C1 inhibitor, and prevented cleavage and consumption of high-molecular-weight kininogen. Activation of several coagulation factors and fibrinolytic enzymes was also prevented. D-dimer levels exhibited a profound increase in the untreated animals but not in the treated animals. The antibody also blocked the increase in plasma biomarkers of inflammation and cell damage, including tumor necrosis factor, interleukin (IL)-1β, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, nucleosomes, and myeloperoxidase. Based on clinical presentation and circulating biomarkers, inhibition of FXII prevented fever, terminal hypotension, respiratory distress, and multiorgan failure. All animals receiving 5C12 had milder and transient clinical symptoms and were asymptomatic at day 7, whereas untreated control animals suffered irreversible multiorgan failure and had to be euthanized within 2 days after the bacterial challenge. This study confirms and extends our previous finding that at least 2 enzymes of the contact activation complex, FXIa and FXIIa, play critical roles in the development of an acute and terminal inflammatory response in baboons challenged with heat-inactivated S aureus.
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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.