{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:16:51Z","timestamp":1790745411871,"version":"4.1.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>We investigated the coregulation of thrombin and fibrin as blood flows over a procoagulant surface.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Using microfluidic perfusion of factor XIIa-inhibited human whole blood (200 s\n              <jats:sup>\u22121<\/jats:sup>\n              wall shear rate) over a 250-\u03bcm long patch of collagen\/TF (tissue factor; \u22481 molecule per \u03bcm\n              <jats:sup>2<\/jats:sup>\n              ) and immunoassays of the effluent for F1.2 (prothrombin fragment 1.2), TAT (thrombin\u2013antithrombin complex), and D-dimer (post\u2013end point plasmin digest), we sought to establish the transient mass balance for clotting under venous flow. F1.2 (but almost no free thrombin detected via TAT assay) continually eluted from clots when fibrin was allowed to form. Low-dose fluorescein-Phe-Pro-Arg-chloromethylketone stained fibrin-bound thrombin\u2014a staining ablated by anti\u2013\u03b3\u2032-fibrinogen or the fibrin inhibitor glypro-arg-pro but highly resistant to 7-minute buffer rinse, demonstrating tight binding of thrombin to \u03b3\u2032-fibrin. With fibrin polymerizing for 500 seconds, 92\u2009000 thrombin molecules and 203\u2009000 clot-associated fibrin monomer equivalents were generated per TF molecule (or per \u03bcm\n              <jats:sup>2<\/jats:sup>\n              ). Fibrin reached 15 mg\/mL in the pore space (porosity \u22480.5) of a 15-\u03bcm-thick thrombus core by 500 seconds and 30 mg\/mL by 800 seconds. For a known rate of \u224860 FPA (fibrinopeptide-A) per thrombin per second, each thrombin molecule generated only 3 fibrin monomer equivalents during 500 seconds, indicating an intraclot thrombin half-life of \u224870 ms, much shorter than its diffusional escape time (\u224810 seconds). By 800 seconds, gly-pro-arg-pro allowed 4-fold more F1.2 generation, consistent with gly-pro-arg-pro ablating fibrin\u2019s antithrombin-I activity and facilitating thrombin-mediated FXIa activation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Under flow, fibrinogen continually penetrates the clot, and \u03b3\u2032-fibrin regulates thrombin.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.118.310906","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T09:05:38Z","timestamp":1525338338000},"page":"1528-1536","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Establishing the Transient Mass Balance of Thrombosis"],"prefix":"10.1161","volume":"38","author":[{"given":"Shu","family":"Zhu","sequence":"first","affiliation":[{"name":"From the Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L.","family":"Diamond","sequence":"additional","affiliation":[{"name":"From the Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, 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