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Compared to fibrin generation, decreased platelet deposition in haemophilic blood flow is more easily rescued with recombinant factor VIIa (<jats:styled-content style=\"fixed-case\">rFVII<\/jats:styled-content>a), whereas <jats:styled-content style=\"fixed-case\">rFVII<\/jats:styled-content>a requires <jats:styled-content style=\"fixed-case\">FXII<\/jats:styled-content>a participation to generate fibrin when tissue factor (<jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content>) is absent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>Perfusion of haemophilic whole blood (WB) over collagen\/<jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content> surfaces was used to determine whether <jats:styled-content style=\"fixed-case\">rFVII<\/jats:styled-content>a\/<jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content> was sufficient to bypass poor <jats:styled-content style=\"fixed-case\">FIX<\/jats:styled-content>a\/<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>a function in blood from patients with haemophilia A and B.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole blood treated with high\u2010dose corn trypsin inhibitor (40 \u03bcg mL<jats:sup>\u22121<\/jats:sup>) from seven healthy donors and 10 patients was perfused over fibrillar collagen presenting low or high <jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content><jats:sub>low<\/jats:sub> or <jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content><jats:sub>high<\/jats:sub>) at wall shear rate of 100 s<jats:sup>\u22121<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>With <jats:styled-content style=\"fixed-case\">WB<\/jats:styled-content> from healthy controls, platelet deposition and fibrin accumulation increased as <jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content> increased. Factor\u2010deficient <jats:styled-content style=\"fixed-case\">WB<\/jats:styled-content> (1\u20133% of normal) displayed striking deficits in platelet deposition and fibrin formation at either <jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content><jats:sub>low<\/jats:sub> or <jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content><jats:sub>high<\/jats:sub>. In contrast, mildly factor\u2010deficient <jats:styled-content style=\"fixed-case\">WB<\/jats:styled-content> (14\u201332%) supported fibrin formation under flow on <jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content><jats:sub>high<\/jats:sub>\/collagen. With either <jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content><jats:sub>low<\/jats:sub> or <jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content><jats:sub>high<\/jats:sub>, exogenously added <jats:styled-content style=\"fixed-case\">rFVII<\/jats:styled-content>a (20 n<jats:sc>m<\/jats:sc>) increased platelet deposition and fibrin accumulation in <jats:styled-content style=\"fixed-case\">WB<\/jats:styled-content> from factor\u2010deficient patients (1\u20133% of normal) to levels commensurate with untreated healthy WB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The absence of <jats:styled-content style=\"fixed-case\">FIX<\/jats:styled-content>a\/<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>a in patients with severe haemophilia results in deficits in fibrin formation that cannot be rescued by wall\u2010derived <jats:styled-content style=\"fixed-case\">TF <\/jats:styled-content><jats:italic>ex vivo<\/jats:italic>. The effects of <jats:styled-content style=\"fixed-case\">rFVII<\/jats:styled-content>a on platelet adhesion and <jats:styled-content style=\"fixed-case\">rFVII<\/jats:styled-content>a\/<jats:styled-content style=\"fixed-case\">TF<\/jats:styled-content> can act together to reinforce thrombin generation, platelet deposition and fibrin formation under flow.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13259","type":"journal-article","created":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T13:03:19Z","timestamp":1493989399000},"page":"759-768","source":"Crossref","is-referenced-by-count":7,"title":["Recombinant factor <scp>VII<\/scp>a addition to haemophilic blood perfused over collagen\/tissue factor can sufficiently bypass the factor <scp>IX<\/scp>a\/<scp>VIII<\/scp>a defect to rescue fibrin generation"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6950-5045","authenticated-orcid":false,"given":"R.","family":"Li","sequence":"first","affiliation":[{"name":"Institute for Medicine and Engineering Department of Chemical and Biomolecular Engineering University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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