{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:18:11Z","timestamp":1787329091421,"version":"build-2736575974"},"reference-count":48,"publisher":"Georg Thieme Verlag KG","issue":"08","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hamamatsu University School of Medicine"},{"name":"HUSM Grant-in-Aid"},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["KAKENHI Grant Number JP22H03172"],"award-info":[{"award-number":["KAKENHI Grant Number JP22H03172"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004330","name":"Smoking Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004330","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004330","name":"Smoking Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004330","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fibrinolysis is spatiotemporally well-regulated and greatly influenced by activated platelets and coagulation activity. Our previous real-time imaging analyses revealed that clotting commences on activated platelet surfaces, resulting in uneven-density fibrin structures, and that fibrinolysis initiates in dense fibrin regions and extends to the periphery. Despite the widespread clinical use of direct oral anticoagulants (DOACs), their impact on thrombin-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) and fibrinolysis remains unclear. Here, we investigated the effects of different DOACs on the TAFI-mediated inhibition of fibrinolysis.<\/jats:p>\n                  <jats:p>Using human platelet-containing plasma, we performed turbidimetric assays, thrombin generation assays, and confocal laser scanning microscopy to assess the effects of anticoagulants on fibrinolysis.<\/jats:p>\n                  <jats:p>Activated platelets-prolonged plasma clot lysis time, shortened by activated TAFI inhibitor (TAFIaI), positively correlated with the amount of thrombin generated. Rivaroxaban (an activated factor X inhibitor) and dabigatran (a direct thrombin inhibitor) dose-dependently shortened lysis time comparably. The highest concentration of DOACs showed no further shortening of lysis time with TAFIaI. The fibrin network structures initiated by activated platelets and the localization of fluorescently labeled plasminogen were unique for these two drugs. Rivaroxaban maintained an uneven fibrin network but promoted faster plasminogen accumulation and fibrinolysis from outside dense fibrin regions. Conversely, dabigatran resulted in a more even fibrin network, with fibrinolysis starting from the activated platelets and propagating to the periphery. Visualizing and analyzing the patterns of fibrin network formation, plasminogen accumulation, and fibrinolysis provide new insights into the specific impact of anticoagulants on coagulation and fibrinolysis.<\/jats:p>","DOI":"10.1055\/a-2497-4213","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T19:20:04Z","timestamp":1736450404000},"page":"766-778","source":"Crossref","is-referenced-by-count":7,"title":["Real-Time Imaging of Platelet-Initiated Plasma Clot Formation and Lysis Unveils Distinct Impacts of Anticoagulants"],"prefix":"10.1055","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4833-8580","authenticated-orcid":false,"given":"Yuko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitty S.","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan"},{"name":"Department of Transfusion Medicine & Immunohematology, Christian Medical College Vellore, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideto","family":"Sano","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan"},{"name":"Department of Physiology, Tokai University School of Medicine, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanami","family":"Morooka","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Honkura","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsumei","family":"Urano","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan"},{"name":"Shizuoka Graduate University of Public Health, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1016\/S0140-6736(20)32439-9","article-title":"Direct oral anticoagulants: evidence and unresolved issues","volume":"396","author":"N Chan","year":"2020","journal-title":"Lancet"},{"issue":"13","key":"ref2","doi-asserted-by":"crossref","first-page":"e017559","DOI":"10.1161\/JAHA.120.017559","article-title":"Direct oral anticoagulant use: a practical guide to common clinical challenges","volume":"9","author":"A 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enhances tPA-induced thrombolysis in mouse microthrombi: evidence from intravital imaging analysis","volume":"210","author":"N S Mathews","year":"2022","journal-title":"Thromb Res"},{"issue":"01","key":"ref30","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1159\/000071636","article-title":"Calibrated automated thrombin generation measurement in clotting plasma","volume":"33","author":"H C Hemker","year":"2003","journal-title":"Pathophysiol Haemost Thromb"},{"issue":"04","key":"ref31","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1160\/TH13-04-0345","article-title":"Simultaneous measurement of thrombin and plasmin generation to assess the interplay between coagulation and fibrinolysis","volume":"110","author":"T Matsumoto","year":"2013","journal-title":"Thromb Haemost"},{"issue":"02","key":"ref32","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/rth2.12044","article-title":"Assessment of the effect of direct oral anticoagulants dabigatran, 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