{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T12:04:09Z","timestamp":1771675449813,"version":"3.50.1"},"reference-count":52,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,2,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Staphylococcus aureus infections can produce systemic bacteremia and inflammation in humans, which may progress to severe sepsis or septic shock, even with appropriate antibiotic treatment. Sepsis may be associated with disseminated intravascular coagulation and consumptive coagulopathy. In some types of mouse infection models, the plasma coagulation protein factor XI (FXI) contributes to the pathogenesis of sepsis. We hypothesize that FXI also contributes to the pathogenesis of sepsis in primates, and that pharmacological interference with FXI will alter the outcome of Staphylococcus aureus\u2013induced lethality in a baboon model. Pretreatment of baboons with the anti-FXI antibody 3G3, a humanized variant of the murine monoclonal 14E11 that blocks FXI activation by FXIIa, substantially reduced the activation of coagulation, as reflected by clotting times and plasma complexes of coagulation proteases (FXIIa, FXIa, FIXa, FXa, FVIIa, and thrombin) with serpins (antithrombin or C1 inhibitor) following infusion of heat-inactivated S aureus. 3G3 treatment reduced fibrinogen and platelet consumption, fibrin deposition in tissues, neutrophil activation and accumulation in tissues, cytokine production, kininogen cleavage, cell death, and complement activation. Overall, 3G3 infusion protected the structure and function of multiple vital organs, including lung, heart, liver, and kidney. All treated animals reached the end point survival (7 days), whereas all nontreated animals developed terminal organ failure within 28 hours. We conclude that FXI plays a role in the pathogenesis of S aureus\u2013induced disseminated intravascular coagulation and lethality in baboons. The results provide proof of concept for future therapeutic interventions that may prevent sepsis-induced organ failure and save lives in certain forms of sepsis.<\/jats:p>","DOI":"10.1182\/bloodadvances.2018029983","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T21:55:29Z","timestamp":1551218129000},"page":"658-669","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":71,"title":["Inhibition of contact-mediated activation of factor XI protects baboons against S aureus\u2013induced organ damage and death"],"prefix":"10.1182","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9590-6160","authenticated-orcid":false,"given":"Robert","family":"Silasi","sequence":"first","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4177-9095","authenticated-orcid":false,"given":"Ravi Shankar","family":"Keshari","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8619-0893","authenticated-orcid":false,"given":"Cristina","family":"Lupu","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9088-6199","authenticated-orcid":false,"given":"Walter Janse","family":"Van Rensburg","sequence":"additional","affiliation":[{"name":"Human Molecular Biology Unit, University of the Free State, Bloemfontein, South Africa;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7112-564X","authenticated-orcid":false,"given":"Hala","family":"Chaaban","sequence":"additional","affiliation":[{"name":"Neonatal and Perinatal Section, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6827-3783","authenticated-orcid":false,"given":"Girija","family":"Regmi","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2348-1444","authenticated-orcid":false,"given":"Aleksandr","family":"Shamanaev","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph J.","family":"Shatzel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"},{"name":"Division of Hematology & Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Puy","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina U.","family":"Lorentz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"},{"name":"Aronora, Inc, Portland, OR; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik I.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"},{"name":"Aronora, Inc, Portland, OR; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8142-8014","authenticated-orcid":false,"given":"David","family":"Gailani","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6212-2247","authenticated-orcid":false,"given":"Andr\u00e1s","family":"Gruber","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"},{"name":"Division of Hematology & Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR;"},{"name":"Aronora, Inc, Portland, OR; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9481-0124","authenticated-orcid":false,"given":"Owen J. 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