{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T08:09:18Z","timestamp":1778659758000,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,10,14]],"date-time":"2014-10-14T00:00:00Z","timestamp":1413244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL103419"],"award-info":[{"award-number":["HL103419"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL120877"],"award-info":[{"award-number":["HL120877"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["H30MC24050"],"award-info":[{"award-number":["H30MC24050"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>In prior microfluidic studies with haemophilic blood perfused over collagen, we found that a severe deficiency (&lt;1% factor level) reduced platelet and fibrin deposition, while a moderate deficiency (1\u20135%) only reduced fibrin deposition. We investigated: (i) the differential effect of <jats:styled-content style=\"fixed-case\">rFVII<\/jats:styled-content>a (0.04\u201320\u00a0n<jats:sc>m<\/jats:sc>) on platelet and fibrin deposition, and (ii) the contribution of the contact pathway to <jats:styled-content style=\"fixed-case\">rFVII<\/jats:styled-content>a\u2010induced haemophilic blood clotting. Haemophilic or healthy blood with low and high corn trypsin inhibitor (CTI, 4 or 40\u00a0\u03bcg\u00a0<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content><jats:sup>\u22121<\/jats:sup>) was perfused over collagen at an initial venous wall shear rate of 100\u00a0s<jats:sup>\u22121<\/jats:sup>. At 100\u00a0s<jats:sup>\u22121<\/jats:sup> wall shear rate, where FXIIa leads to thrombin production without added tissue factor, FXI\u2010deficient blood (3%) or severely FVIII\u2010deficient blood (&lt;1%) produced no fibrin at either CTI level. Whereas <jats:styled-content style=\"fixed-case\">rFVII<\/jats:styled-content>a potently enhanced platelet deposition, fibrin generation was not rescued. Distinct from the high CTI condition, engagement of the contact pathway (low CTI) in moderately FVIII\u2010deficient (3%) or moderately FIX\u2010deficient blood (5%) resulted in enhanced platelet and fibrin deposition following 4\u00a0n<jats:sc>m <\/jats:sc><jats:styled-content style=\"fixed-case\">rFVII<\/jats:styled-content>a supplementation. In mildly FVIII\u2010deficient blood (15%) at &lt;24\u00a0h since haemostatic therapy, <jats:styled-content style=\"fixed-case\">rFVII<\/jats:styled-content>a enhanced both platelet and fibrin generation in either CTI condition although fibrin was produced more quickly and abundantly in low CTI. For tissue factor\u2010free conditions of severe haemophilic blood clotting, we conclude that <jats:styled-content style=\"fixed-case\">rFVII<\/jats:styled-content>a reliably generates low levels of \u2018signaling\u2019 thrombin sufficient to enhance platelet deposition on collagen, but is insufficient to drive fibrin polymerization unless potentiated by the contact pathway.<\/jats:p>","DOI":"10.1111\/hae.12558","type":"journal-article","created":{"date-parts":[[2014,10,14]],"date-time":"2014-10-14T05:39:10Z","timestamp":1413265150000},"page":"266-274","source":"Crossref","is-referenced-by-count":16,"title":["Recombinant factor <scp>VII<\/scp>a enhances platelet deposition from flowing haemophilic blood but requires the contact pathway to promote fibrin deposition"],"prefix":"10.1111","volume":"21","author":[{"given":"R.","family":"Li","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering Institute for Medicine and Engineering University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. A.","family":"Panckeri","sequence":"additional","affiliation":[{"name":"Comprehensive Hemophilia and Thrombosis Program Hospital of the University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. F.","family":"Fogarty","sequence":"additional","affiliation":[{"name":"Comprehensive Hemophilia and Thrombosis Program Hospital of the University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. L.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering Institute for Medicine and Engineering University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,10,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200106073442307"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH07-04-0246"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-017988"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2004.00528.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-09-2761"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078732"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2012.198101"},{"key":"e_1_2_8_9_1","first-page":"203","article-title":"Detection of platelet sensitivity to inhibitors of COX\u20101, P2Y1, and P2Y12, using a whole blood microfluidic flow assay","volume":"2","author":"Li R","year":"2013","journal-title":"Thromb Res"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12457"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(80)90381-3"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000950"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.249789"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc200326v"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/b919728a"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03188.x"},{"key":"e_1_2_8_17_1","first-page":"S15","article-title":"A possible mechanism of activated factor VII independent of tissue factor","volume":"9","author":"Monroe DM","year":"1998","journal-title":"Blood Coagul Fibrinolysis"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.4463256.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH10-07-0460"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2010.10.004"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000130465.23430.74"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-270918"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-171066"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V57.1.106.106"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005743107"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-006-6556-7"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.12558","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.12558","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.12558","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.12558","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T17:05:38Z","timestamp":1693155938000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.12558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,14]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1111\/hae.12558"],"URL":"https:\/\/doi.org\/10.1111\/hae.12558","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,14]]}}}