{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T14:18:34Z","timestamp":1768400314492,"version":"3.49.0"},"reference-count":42,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"DOI":"10.13039\/501100000152","name":"Canadian Hemophilia Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000152","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Platelet defects due to hyper-responsive GPIb\u03b1 causing enhanced VWF interaction, counter-intuitively result in bleeding rather than thrombosis. The historical explanation of platelet\/VWF clearance fails to explain mechanisms of impaired haemostasis particularly in light of reported poor platelet binding to fibrinogen. This study aimed to evaluate the defects of platelets with hyper-responsive GPIb\u03b1 and their contribution to impaired in vivo thrombosis. Using the PT-VWD mouse model, platelets from the hTgG233V were compared to control hTgWT mice. Platelets\u2019 pro-coagulant capacity was evaluated using flowcytometry assessment of P-selectin and annexin V. Whole blood platelet aggregation in response to ADP, collagen and thrombin was tested. Clot kinetics using laser injury thrombosis model and the effect of GPIb\u03b1 inhibition in vivo using 6B4; a monoclonal antibody, were evaluated. Thrombin-induced platelet P-selectin and PS exposure were significantly reduced in hTgG233V compared to hTgWT and not signifi-cantly different when compared to unstimulated platelets. The hTgG233V platelets aggregated normally in response to collagen, and had a delayed response to ADP and thrombin, when compared to hTgWT platelets. Laser injury showed significant impairment of in vivo thrombus formation in hTgG233V compared to hTgWT mice. There was a significant lag in in vitro clot formation in turbidity assay but no impairment in thrombin generation was observed using thromboelastography. The in vivo inhibition of GPIb\u03b1 facilitated new \u2013 unstable \u2013 clot formation but did not improve the lag. We conclude platelets with hyper-responsive GPIb\u03b1 have complex intrinsic defects beyond the previously described mechanisms. Abnormal signalling through GPIb\u03b1 and potential therapy using inhibitors require further investigations.<\/jats:p><jats:p>Supplementary Material to this article is available online at www.thrombosis-online.com.<\/jats:p>","DOI":"10.1160\/th16-04-0317","type":"journal-article","created":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T09:52:31Z","timestamp":1482400351000},"page":"543-555","source":"Crossref","is-referenced-by-count":14,"title":["Thrombocytopathy leading to impaired in vivo haemostasis and thrombosis in platelet type von Willebrand disease"],"prefix":"10.1160","volume":"117","author":[{"given":"Harmanpreet","family":"Kaur","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Corscadden","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerry","family":"Ware","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maha","family":"Othman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2017,11,22]]},"reference":[{"key":"10.1160\/TH16-04-0317-1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(96)00122-7"},{"key":"10.1160\/TH16-04-0317-2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1000387"},{"key":"10.1160\/TH16-04-0317-3","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1220331"},{"key":"10.1160\/TH16-04-0317-4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112132"},{"key":"10.1160\/TH16-04-0317-5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.21.7424"},{"key":"10.1160\/TH16-04-0317-6","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000031340.68494.34"},{"key":"10.1160\/TH16-04-0317-7","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1055\/s-0037-1613209","volume":"88","author":"Heemskerk","year":"2002","journal-title":"Thromb Haemost"},{"key":"10.1160\/TH16-04-0317-8","doi-asserted-by":"crossref","first-page":"4397","DOI":"10.1182\/blood.V91.12.4397","volume":"91","author":"Lopez","year":"1998","journal-title":"Blood"},{"key":"10.1160\/TH16-04-0317-9","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13204"},{"key":"10.1160\/TH16-04-0317-10","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1548838"},{"key":"10.1160\/TH16-04-0317-11","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2011.03.003"},{"key":"10.1160\/TH16-04-0317-12","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1281030"},{"key":"10.1160\/TH16-04-0317-13","doi-asserted-by":"publisher","DOI":"10.1160\/TH10-04-0213"},{"key":"10.1160\/TH16-04-0317-14","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1066019"},{"key":"10.1160\/TH16-04-0317-15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06850.x"},{"key":"10.1160\/TH16-04-0317-16","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070417"},{"key":"10.1160\/TH16-04-0317-17","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-210823"},{"key":"10.1160\/TH16-04-0317-18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.050582097"},{"key":"10.1160\/TH16-04-0317-19","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.5.1347"},{"key":"10.1160\/TH16-04-0317-20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701826200"},{"key":"10.1160\/TH16-04-0317-21","doi-asserted-by":"publisher","DOI":"10.1161\/hq0202.102321"},{"key":"10.1160\/TH16-04-0317-22","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1182\/blood.V96.7.2469","volume":"96","author":"Dormann","year":"2000","journal-title":"Blood"},{"key":"10.1160\/TH16-04-0317-23","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-03-145755"},{"key":"10.1160\/TH16-04-0317-24","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8977-7-17"},{"key":"10.1160\/TH16-04-0317-25","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0935"},{"key":"10.1160\/TH16-04-0317-26","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-113274"},{"key":"10.1160\/TH16-04-0317-27","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-381400"},{"key":"10.1160\/TH16-04-0317-28","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jhh.1001447"},{"key":"10.1160\/TH16-04-0317-29","first-page":"172","volume":"18","author":"Tomer","year":"2004","journal-title":"J Biol Regul Homeost Agents"},{"key":"10.1160\/TH16-04-0317-30","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-266080"},{"key":"10.1160\/TH16-04-0317-31","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.015990"},{"key":"10.1160\/TH16-04-0317-32","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2016.1237625"},{"key":"10.1160\/TH16-04-0317-33","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1160\/TH06-06-0297","volume":"96","author":"Fontayne","year":"2006","journal-title":"Thromb Haemost"},{"key":"10.1160\/TH16-04-0317-34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.11189"},{"key":"10.1160\/TH16-04-0317-35","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7827(03)00025-0"},{"key":"10.1160\/TH16-04-0317-36","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69458"},{"key":"10.1160\/TH16-04-0317-37","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2006.11.001"},{"key":"10.1160\/TH16-04-0317-38","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0197-4"},{"key":"10.1160\/TH16-04-0317-39","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2143(96)90116-X"},{"key":"10.1160\/TH16-04-0317-40","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-04-638387"},{"key":"10.1160\/TH16-04-0317-41","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1998.00923.x"},{"key":"10.1160\/TH16-04-0317-42","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12934"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1160\/TH16-04-0317.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T19:20:51Z","timestamp":1658258451000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1160\/TH16-04-0317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":42,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2017,11,21]]},"published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1160\/th16-04-0317","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017]]}}}