{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T23:24:04Z","timestamp":1787095444378,"version":"build-2736575974"},"reference-count":105,"publisher":"Georg Thieme Verlag KG","issue":"06","funder":[{"name":"National Institutes of Health, National Heart, Lung, and Blood Institute","award":["R01HL144133"],"award-info":[{"award-number":["R01HL144133"]}]},{"name":"National Institutes of Health, National Heart, Lung, and Blood Institute","award":["R01HL101972"],"award-info":[{"award-number":["R01HL101972"]}]},{"name":"Institute of Allergy and Infectious Diseases","award":["R01AI157037"],"award-info":[{"award-number":["R01AI157037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lipopolysaccharide (LPS), a key component of the outer membrane of Gram-negative bacteria, is well-known for its role in triggering inflammation via innate immune receptors. However, evidence suggests that LPS can influence coagulation, in part through activation of the contact pathway. Recent studies from our group and others demonstrate that the supramolecular organization and physicochemical properties of LPS\u2014such as aggregate size, surface charge, and chemotype\u2014critically determine the ability of LPS to activate coagulation factor XII (FXII). While monomeric LPS can modulate FXII activity, only aggregated forms of LPS (e.g., micelles) function as a procoagulant surface, initiating contact activation. This review synthesizes current knowledge on LPS structural heterogeneity and explores how the biophysical properties of LPS govern supramolecular assembly in aqueous environments, ultimately dictating interactions with the contact activation pathway. We further discuss the possible mechanisms by which LPS-driven FXII activation contributes to thromboinflammatory disorders, including disseminated intravascular coagulation and sepsis-associated vascular leakage. Finally, we highlight novel therapeutic strategies\u2014from FXIIa inhibitors to molecules that disrupt LPS supramolecular structures\u2014as potential interventions to mitigate coagulation-driven pathology during bacterial infections. These insights not only reflect our growing understanding of infection-associated thrombosis but may also pave the way for targeted therapies in sepsis and other thromboinflammatory conditions.<\/jats:p>","DOI":"10.1055\/a-2716-6782","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T23:29:17Z","timestamp":1759879757000},"page":"683-691","source":"Crossref","is-referenced-by-count":3,"title":["Lipopolysaccharide and Coagulation Factor XII: Biophysics of Contact Activation in Infection"],"prefix":"10.1055","volume":"52","author":[{"given":"Andr\u00e9 L.","family":"Lira","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn C.","family":"Drew","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Puy","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J.","family":"Shatzel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, United States"},{"name":"Division of Hematology and Medical Oncology, School of Medicine, Oregon Health and Science University, Portland, Oregon, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen J.T.","family":"McCarty","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.3389\/fimmu.2019.02569","article-title":"Understanding infection-induced thrombosis: Lessons learned from animal models","volume":"10","author":"N Beristain-Covarrubias","year":"2019","journal-title":"Front Immunol"},{"issue":"04","key":"ref2","doi-asserted-by":"crossref","first-page":"100091","DOI":"10.1016\/j.bvth.2025.100091","article-title":"Bacterial infection and activation of the contact pathway of coagulation","volume":"2","author":"A L Lira","year":"2025","journal-title":"Blood Vessel Thromb Hemost"},{"issue":"13","key":"ref3","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1182\/blood.2020007208","article-title":"Disseminated intravascular coagulation and its immune mechanisms","volume":"139","author":"N I 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