{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T15:59:35Z","timestamp":1776095975325,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000028","name":"Institute of Circulatory and Respiratory Health","doi-asserted-by":"publisher","award":["201603PJT\u2010364832"],"award-info":[{"award-number":["201603PJT\u2010364832"]}],"id":[{"id":"10.13039\/501100000028","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Calibrated automated thrombograms (CAT) with platelet\u2010poor (PPP) and platelet\u2010rich plasma (PRP) have provided useful insights on bleeding disorders. We used CAT to assess thrombin generation (TG) in Quebec platelet disorder (QPD)\u2014a bleeding disorder caused by a <jats:italic>PLAU<\/jats:italic> duplication mutation that increases platelet (but not plasma) urokinase plasminogen activator (uPA), leading to intraplatelet (but not systemic) plasmin generation that degrades \u03b1\u2010granule proteins and causes platelet (but not plasma) factor V (FV) deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Calibrated automated thrombograms was used to test QPD (n\u00a0=\u00a07) and control (n\u00a0=\u00a022) PPP and PRP, with or without added tranexamic acid (TXA). TG endpoints were evaluated for relationships to platelet FV and uPA, plasma FV and tissue factor pathway inhibitor (TFPI) levels, and bleeding scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Quebec platelet disorder PPP TG was normal whereas QPD PRP had reduced endogenous thrombin potential and peak thrombin concentrations (<jats:italic>P<\/jats:italic> values\u00a0&lt;\u00a0.01), proportionate to the platelet FV deficiency (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0\u2265\u00a00.81), but unrelated to platelet uPA, plasma FV, or bleeding scores. QPD TG abnormalities were not associated with TFPI abnormalities and were not reproduced by adding uPA to control PRP. TXA increased QPD and control PRP TG more than PPP TG, but it did not fully correct QPD PRP TG abnormalities or improve TG by plasminogen\u2010deficient plasma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Quebec platelet disorder results in a platelet\u2010specific TG defect, proportionate to the loss of platelet FV, that is improved but not fully corrected by TXA. Our study provides an interesting example of why it is important to assess both PRP and PPP TG in bleeding disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijlh.13302","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T22:46:35Z","timestamp":1596753995000},"page":"801-809","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Thrombin generation abnormalities in Quebec platelet disorder"],"prefix":"10.1111","volume":"42","author":[{"given":"Justin G.","family":"Brunet","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University Hamilton ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanmya","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University Hamilton ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8859-4119","authenticated-orcid":false,"given":"Subia","family":"Tasneem","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University Hamilton ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4451-0921","authenticated-orcid":false,"given":"Minggao","family":"Liang","sequence":"additional","affiliation":[{"name":"Genetics and Genome Biology The Hospital for Sick Children Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4015-3066","authenticated-orcid":false,"given":"Michael D.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Genetics and Genome Biology The Hospital for Sick Children Toronto ON Canada"},{"name":"Molecular Genetics University of Toronto Toronto ON Canada"},{"name":"Heart &amp; Stroke Richard Lewar Centre of Excellence in Cardiovascular Research Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georges E.","family":"Rivard","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Sainte Justine Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2843-0817","authenticated-orcid":false,"given":"Catherine P. 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