{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:03:11Z","timestamp":1785409391926,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Faisal Specialist Hospital and Research Center"},{"id":[{"id":"https:\/\/ror.org\/05n0wgt02","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ministry of Education of Saudi Arabia","award":["ATA-J\/73\/44"],"award-info":[{"award-number":["ATA-J\/73\/44"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Tissue factor (TF)-expressing cancer cells and their extracellular vesicles (CaCe-dEVs) are key drivers of cancer-associated hypercoagulability and vascular dysfunction. While low-molecular-weight heparins (LMWHs) and direct FXa inhibitors are standard therapies for cancer-associated thrombosis, their direct effects on cancer cell procoagulant potential and endothelial responses remain incompletely defined. This study compared the impact of LMWHs (enoxaparin, tinzaparin), apixaban, and quercetin on cancer cell viability, thrombin generation, and CaCe-dEVs-induced endothelial injury. Methods: Pancreatic (BXPC3) and breast (MCF7) cancer cells and their vesicles were analyzed for TF expression and thrombin generation. Human umbilical vein endothelial cells (HUVECs) were pretreated with each agent prior to vesicle exposure. Cell viability, thrombin generation, and endothelial morphology were assessed using standard assays and microscopy. Results: Tinzaparin and quercetin significantly reduced cancer cell viability, whereas enoxaparin and apixaban showed no cytotoxicity. None of the agents affected HUVEC viability. All suppressed TF-mediated thrombin generation induced by cancer cells, with tinzaparin being most effective in BXPC3 cells. Quercetin exhibited a partial and limited protective effect on endothelial cells against CaCe-dEVs-induced dysfunction, while LMWHs and apixaban did not prevent endothelial damage. Conclusions: These findings suggest that LMWHs, apixaban, and quercetin modulate cancer-cell-driven hypercoagulability beyond anticoagulation, with quercetin and tinzaparin showing additional cytotoxic potential. Such dual effects may reduce thrombosis risk while impacting tumor progression, meriting further investigation.<\/jats:p>","DOI":"10.3390\/cancers18111783","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:06:56Z","timestamp":1780049216000},"page":"1783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enoxaparin, Tinzaparin, and Apixaban Modulate Cancer Cell Procoagulant Activity and Viability: Comparison with Quercetin"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1469-3074","authenticated-orcid":false,"given":"Mohammed A.","family":"Baghdadi","sequence":"first","affiliation":[{"name":"Research Group \u201cCancer\u2013Angiogenesis\u2013Thrombosis and Hemostasis\u201d, Research Team \u201cCancer, Vessels, Biology and Therapeutics\u201d (CaVITE), Saint-Antoine Research Center (CRSA), INSERM UMR_S_938, Saint-Antoine University Hospital, University Institute of Cancerology (UIC), Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Sorbonne University, 75012 Paris, France"},{"name":"Research Center, King Faisal Specialist Hospital and Research Center, Jeddah 23433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1780-8845","authenticated-orcid":false,"given":"Pedro Henrique Fernandes","family":"do Carmo Las Casas","sequence":"additional","affiliation":[{"name":"Research Group \u201cCancer\u2013Angiogenesis\u2013Thrombosis and Hemostasis\u201d, Research Team \u201cCancer, Vessels, Biology and Therapeutics\u201d (CaVITE), Saint-Antoine Research Center (CRSA), INSERM UMR_S_938, Saint-Antoine University Hospital, University Institute of Cancerology (UIC), Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Sorbonne University, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Mbemba","sequence":"additional","affiliation":[{"name":"Research Group \u201cCancer\u2013Angiogenesis\u2013Thrombosis and Hemostasis\u201d, Research Team \u201cCancer, Vessels, Biology and Therapeutics\u201d (CaVITE), Saint-Antoine Research Center (CRSA), INSERM UMR_S_938, Saint-Antoine University Hospital, University Institute of Cancerology (UIC), Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Sorbonne University, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Rousseau","sequence":"additional","affiliation":[{"name":"Research Group \u201cCancer\u2013Angiogenesis\u2013Thrombosis and Hemostasis\u201d, Research Team \u201cCancer, Vessels, Biology and Therapeutics\u201d (CaVITE), Saint-Antoine Research Center (CRSA), INSERM UMR_S_938, Saint-Antoine University Hospital, University Institute of Cancerology (UIC), Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Sorbonne University, 75012 Paris, France"},{"name":"Clinical Research Department, Diagnostica Stago, 92230 Gennevilliers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-0339","authenticated-orcid":false,"given":"Prakasha","family":"Kempaiah","sequence":"additional","affiliation":[{"name":"Thrombosis and Hemostasis Research Laboratories, Center of Translational Research and Education (CTRE), Loyola University Stritch School of Medicine, Maywood, Chicago, IL 60153, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey A.","family":"Svistunov","sequence":"additional","affiliation":[{"name":"Thrombosis Center, Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Bitsadze","sequence":"additional","affiliation":[{"name":"Research Group \u201cCancer\u2013Angiogenesis\u2013Thrombosis and Hemostasis\u201d, Research Team \u201cCancer, Vessels, Biology and Therapeutics\u201d (CaVITE), Saint-Antoine Research Center (CRSA), INSERM UMR_S_938, Saint-Antoine University Hospital, University Institute of Cancerology (UIC), Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Sorbonne University, 75012 Paris, France"},{"name":"Thrombosis Center, Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5368-9022","authenticated-orcid":false,"given":"Mich\u00e8le","family":"Sabbah","sequence":"additional","affiliation":[{"name":"Research Group \u201cCancer\u2013Angiogenesis\u2013Thrombosis and Hemostasis\u201d, Research Team \u201cCancer, Vessels, Biology and Therapeutics\u201d (CaVITE), Saint-Antoine Research Center (CRSA), INSERM UMR_S_938, Saint-Antoine University Hospital, University Institute of Cancerology (UIC), Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Sorbonne University, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawed","family":"Fareed","sequence":"additional","affiliation":[{"name":"Thrombosis and Hemostasis Research Laboratories, Center of Translational Research and Education (CTRE), Loyola University Stritch School of Medicine, Maywood, Chicago, IL 60153, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8120-4782","authenticated-orcid":false,"given":"Patrick","family":"Van Dreden","sequence":"additional","affiliation":[{"name":"Research Group \u201cCancer\u2013Angiogenesis\u2013Thrombosis and Hemostasis\u201d, Research Team \u201cCancer, Vessels, Biology and Therapeutics\u201d (CaVITE), Saint-Antoine Research Center (CRSA), INSERM UMR_S_938, Saint-Antoine University Hospital, University Institute of Cancerology (UIC), Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Sorbonne University, 75012 Paris, France"},{"name":"Clinical Research Department, Diagnostica Stago, 92230 Gennevilliers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3268-8597","authenticated-orcid":false,"given":"Varvara","family":"Trachana","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3735-7663","authenticated-orcid":false,"given":"Eleftheria","family":"Lefkou","sequence":"additional","affiliation":[{"name":"Research Group \u201cCancer\u2013Angiogenesis\u2013Thrombosis and Hemostasis\u201d, Research Team \u201cCancer, Vessels, Biology and Therapeutics\u201d (CaVITE), Saint-Antoine Research Center (CRSA), INSERM UMR_S_938, Saint-Antoine University Hospital, University Institute of Cancerology (UIC), Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Sorbonne University, 75012 Paris, France"},{"name":"Hematology-Transfusion Medicine Department, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2316-6348","authenticated-orcid":false,"given":"Grigoris","family":"Gerotziafas","sequence":"additional","affiliation":[{"name":"Research Group \u201cCancer\u2013Angiogenesis\u2013Thrombosis and Hemostasis\u201d, Research Team \u201cCancer, Vessels, Biology and Therapeutics\u201d (CaVITE), Saint-Antoine Research Center (CRSA), INSERM UMR_S_938, Saint-Antoine University Hospital, University Institute of Cancerology (UIC), Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Sorbonne University, 75012 Paris, France"},{"name":"Thrombosis and Hemostasis Research Laboratories, Center of Translational Research and Education (CTRE), Loyola University Stritch School of Medicine, Maywood, Chicago, IL 60153, USA"},{"name":"Thrombosis Center, Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia"},{"name":"VAS-European Independent Foundation in Angiology\/Vascular Medicine, 20157 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1111\/jth.14891","article-title":"Thrombin generation predicts early recurrence in breast cancer patients","volume":"18","author":"Marchetti","year":"2020","journal-title":"J. Thromb. 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