{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:58:50Z","timestamp":1790863130159,"version":"4.1.0"},"reference-count":35,"publisher":"Georg Thieme Verlag KG","issue":"03","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2012]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The natural anticoagulant protein S contains a so-called thrombin-sensitive region (TSR), which is susceptible to proteolytic cleavage. We have previously shown that a platelet-associated protease is able to cleave protein S under physiological plasma conditions in vitro. The aim of the present study was to investigate the relation between platelet-associated protein S cleaving activity and in vivo protein S cleavage, and to evaluate the impact of in vivo protein S cleavage on its anticoagulant activity. Protein S cleavage in healthy subjects and in thrombocytopenic and thrombocythaemic patients was evaluated by immunological techniques. Concentration of cleaved and intact protein S was correlated to levels of activated protein C (APC)-dependent and APC-independent protein S anticoagulant activity. In plasma from healthy volunteers 25% of protein S is cleaved in the TSR. While in plasma there was a clear positive correlation between levels of intact protein S and both APC-dependent and APC-independent protein S anticoagulant activities, these correlations were absent for cleaved protein S. Protein S cleavage was significantly increased in patients with essential thrombocythaemia (ET) and significantly reduced in patients with chemotherapy-induced thrombocytopenia. In ET patients on cytoreductive therapy, both platelet count and protein S cleavage returned to normal values. Accordingly, platelet transfusion restored cleavage of protein S to normal values in patients with chemotherapy-induced thrombocytopenia. In conclusion, proteases from platelets seem to contribute to the presence of cleaved protein S in the circulation and may enhance the coagulation response in vivo by down regulating the anticoagulant activity of protein S.<\/jats:p>","DOI":"10.1160\/th11-07-0457","type":"journal-article","created":{"date-parts":[[2012,2,9]],"date-time":"2012-02-09T12:55:41Z","timestamp":1328792141000},"page":"468-476","source":"Crossref","is-referenced-by-count":22,"title":["Platelet-mediated proteolytic down regulation of the anticoagulant activity of protein S in individuals with haematological malignancies"],"prefix":"10.1160","volume":"107","author":[{"given":"Ilze","family":"Dienava-Verdoold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina R.","family":"Marchetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liane C. J.","family":"te Boome","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Russo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Falanga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry R","family":"Koene","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"Mertens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herm Jan M.","family":"Brinkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2017,11,22]]},"reference":[{"key":"10.1160\/TH11-07-0457-1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-209031"},{"key":"10.1160\/TH11-07-0457-2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39325"},{"key":"10.1160\/TH11-07-0457-3","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.10103"},{"key":"10.1160\/TH11-07-0457-4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.780759"},{"key":"10.1160\/TH11-07-0457-5","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000168421.13467.82"},{"key":"10.1160\/TH11-07-0457-6","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.177436"},{"key":"10.1160\/TH11-07-0457-7","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-123174"},{"key":"10.1160\/TH11-07-0457-8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07366.x"},{"key":"10.1160\/TH11-07-0457-9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.19.11521"},{"key":"10.1160\/TH11-07-0457-10","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3600499"},{"key":"10.1160\/TH11-07-0457-11","doi-asserted-by":"publisher","DOI":"10.1006\/bcmd.2002.0558"},{"key":"10.1160\/TH11-07-0457-12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01647.x"},{"key":"10.1160\/TH11-07-0457-13","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1055\/s-0037-1614075","volume":"84","author":"Morboeuf","year":"2000","journal-title":"Thromb Haemost"},{"key":"10.1160\/TH11-07-0457-14","doi-asserted-by":"publisher","DOI":"10.1097\/00001721-199110000-00003"},{"key":"10.1160\/TH11-07-0457-15","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1042\/bj2090837","volume":"209","author":"Dahlb\u00e4ck","year":"1983","journal-title":"Biochem J"},{"key":"10.1160\/TH11-07-0457-16","doi-asserted-by":"publisher","DOI":"10.3109\/00365519309088420"},{"key":"10.1160\/TH11-07-0457-17","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112822"},{"key":"10.1160\/TH11-07-0457-18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-164087"},{"key":"10.1160\/TH11-07-0457-19","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1055\/s-0038-1648880","volume":"72","author":"Meijer-Huizinga","year":"1994","journal-title":"Thromb Haemost"},{"key":"10.1160\/TH11-07-0457-20","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1182\/blood.V79.12.3203.bloodjournal79123203","volume":"79","author":"Griffin","year":"1992","journal-title":"Blood"},{"key":"10.1160\/TH11-07-0457-21","doi-asserted-by":"publisher","DOI":"10.1159\/000071636"},{"key":"10.1160\/TH11-07-0457-22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-1146"},{"key":"10.1160\/TH11-07-0457-23","doi-asserted-by":"crossref","first-page":"3993","DOI":"10.1016\/S0021-9258(18)53569-9","volume":"268","author":"Hackeng","year":"1993","journal-title":"J Biol Chem"},{"key":"10.1160\/TH11-07-0457-24","doi-asserted-by":"crossref","first-page":"21051","DOI":"10.1016\/S0021-9258(17)31928-2","volume":"269","author":"Hackeng","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1160\/TH11-07-0457-25","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1182\/blood.V66.6.1452.1452","volume":"66","author":"Schwarz","year":"1985","journal-title":"Blood."},{"key":"10.1160\/TH11-07-0457-26","doi-asserted-by":"publisher","DOI":"10.1373\/49.4.575"},{"key":"10.1160\/TH11-07-0457-27","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1160\/TH08-04-0242","volume":"100","author":"Damon","year":"2008","journal-title":"Thromb Haemost."},{"key":"10.1160\/TH11-07-0457-28","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.021923"},{"key":"10.1160\/TH11-07-0457-29","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1055\/s-0038-1661291","volume":"53","author":"Bertina","year":"1985","journal-title":"Thromb Haemost."},{"key":"10.1160\/TH11-07-0457-30","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1160\/TH03-03-0174","volume":"90","author":"Malm","year":"2003","journal-title":"Thromb Haemost."},{"key":"10.1160\/TH11-07-0457-31","doi-asserted-by":"publisher","DOI":"10.1021\/bi980520v"},{"key":"10.1160\/TH11-07-0457-32","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1160\/TH07-08-0495","volume":"99","author":"Gale","year":"2008","journal-title":"Thromb Haemost"},{"key":"10.1160\/TH11-07-0457-33","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1042\/bj3190873","volume":"319","author":"Plescia","year":"1996","journal-title":"Biochem J"},{"key":"10.1160\/TH11-07-0457-34","first-page":"1110","volume":"118","author":"Reinhardt","year":"2008","journal-title":"J Clin Invest"},{"key":"10.1160\/TH11-07-0457-35","doi-asserted-by":"publisher","DOI":"10.1160\/TH10-12-0777"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1160\/TH11-07-0457.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T09:57:16Z","timestamp":1640685436000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1160\/TH11-07-0457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012]]},"references-count":35,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2017,11,22]]},"published-print":{"date-parts":[[2012]]}},"URL":"https:\/\/doi.org\/10.1160\/th11-07-0457","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012]]}}}