{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:59:36Z","timestamp":1791809976847,"version":"4.3.4"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T00:00:00Z","timestamp":1360800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Activation of the clotting cascade is central in acute xenograft rejection (<jats:styled-content style=\"fixed-case\">AHXR<\/jats:styled-content>) that occurs when pig organs are transplanted into primates. The coagulopathy reported in this model is a very complex process that involves simultaneously coagulation factors, platelets and phospholipid\u2010bearing cells (i.e., leukocytes, red blood cells, and endothelial cells). Choosing whole blood for coagulation analysis theoretically appears more favorable compared with plasma. Whole blood rotation thromboelastometry (<jats:styled-content style=\"fixed-case\">ROTEM<\/jats:styled-content><jats:sup>\u00ae<\/jats:sup>) is a point\u2010of\u2010care global coagulation analyzer able to evaluate the characteristics of clot formation and lysis by dynamic monitoring. The aim of this study was to record thromboelastographic profiles, performed by <jats:styled-content style=\"fixed-case\">ROTEM<\/jats:styled-content><jats:sup>\u00ae<\/jats:sup>, in a series of immunosuppressed nephrectomized primates that received a life\u2010supporting kidney.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Of the eight primates, n\u00a0=\u00a04 received a pig kidney transgenic for human decay\u2010accelerating factor (<jats:styled-content style=\"fixed-case\">hDAF<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">Ga<\/jats:styled-content>l+); n\u00a0=\u00a02, an \u03b1 1,3\u2010galactosyltransferase gene\u2010knockout (<jats:styled-content style=\"fixed-case\">GT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) pig kidney transgenic for human <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>39, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>55, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>59 and fucosyltransferase (<jats:styled-content style=\"fixed-case\">HTF<\/jats:styled-content>); and n\u00a0=\u00a02, a <jats:styled-content style=\"fixed-case\">GT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> pig kidney transgenic for <jats:styled-content style=\"fixed-case\">hDAF<\/jats:styled-content>. Blood samples were collected before and at least once per week after transplantation till euthanasia. Intrinsic (<jats:styled-content style=\"fixed-case\">INTEM<\/jats:styled-content>) and extrinsic (<jats:styled-content style=\"fixed-case\">EXTEM<\/jats:styled-content>) coagulation pathways and the function of fibrinogen (<jats:styled-content style=\"fixed-case\">FIBTEM<\/jats:styled-content>) were evaluated. Thromboelastographic parameters considered were clotting time (<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>, seconds) and clot formation time (<jats:styled-content style=\"fixed-case\">CFT<\/jats:styled-content>, seconds) in <jats:styled-content style=\"fixed-case\">INTEM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">EXTEM<\/jats:styled-content> and maximum clot firmness (<jats:styled-content style=\"fixed-case\">MCF<\/jats:styled-content>, mm) in <jats:styled-content style=\"fixed-case\">FIBTEM<\/jats:styled-content>. The correlations between CT in <jats:styled-content style=\"fixed-case\">INTEM<\/jats:styled-content> and activated partial thromboplastin time (<jats:styled-content style=\"fixed-case\">aPTT<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">EXTEM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PT<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> CFT<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">INTEM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">EXTEM<\/jats:styled-content>, and platelet counts and <jats:styled-content style=\"fixed-case\">MCF<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">FIBTEM<\/jats:styled-content> and fibrinogen plasma levels were also considered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In all animals, thromboelastographic profiles showed progressive prolongation of <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> (activation of coagulative cascade) in <jats:styled-content style=\"fixed-case\">INTEM<\/jats:styled-content>. A close correspondence was observed between (i) the prolongation of the <jats:styled-content style=\"fixed-case\">CFT<\/jats:styled-content> values (propagation of clot formation), both in <jats:styled-content style=\"fixed-case\">INTEM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">EXTEM<\/jats:styled-content>, and the decrease in platelet counts; (ii) the reduction in <jats:styled-content style=\"fixed-case\">MCF<\/jats:styled-content> values (clot firmness) \u200b\u200bin <jats:styled-content style=\"fixed-case\">FIBTEM<\/jats:styled-content> and the decrease in fibrinogen plasma levels. No concordance between CT in <jats:styled-content style=\"fixed-case\">INTEM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">aPTT<\/jats:styled-content> and between <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">EXTEM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PT<\/jats:styled-content> was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrated that <jats:styled-content style=\"fixed-case\">ROTEM<\/jats:styled-content><jats:sup>\u00ae<\/jats:sup> analyzer could be a useful and complementary tool to study the consumptive coagulopathy, either \u201ccompensated\u201d or \u201cnon\u2010compensated,\u201d that takes place when transgenic pig kidneys are transplanted into primates. Larger and prospective studies are needed to confirm our results and to evaluate the role of <jats:styled-content style=\"fixed-case\">ROTEM<\/jats:styled-content><jats:sup>\u00ae<\/jats:sup> to guide the management of consumptive coagulopathy in order to prolong the survival of the transplanted organ.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12024","type":"journal-article","created":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T08:18:56Z","timestamp":1360829936000},"page":"89-99","source":"Crossref","is-referenced-by-count":13,"title":["Thromboelastographic evaluation of coagulative profiles in pig\u2010to\u2010monkey kidney xenotransplantation"],"prefix":"10.1111","volume":"20","author":[{"given":"Luca","family":"Spiezia","sequence":"first","affiliation":[{"name":"Department of Cardiologic, Thoracic and Vascular Sciences 2nd Chair of Internal Medicine University of Padua Medical School Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Boldrin","sequence":"additional","affiliation":[{"name":"CORIT (Consortium for Research in Organ Transplantation) Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Radu","sequence":"additional","affiliation":[{"name":"Department of Cardiologic, Thoracic and Vascular Sciences 2nd Chair of Internal Medicine University of Padua Medical School Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Bulato","sequence":"additional","affiliation":[{"name":"Department of Cardiologic, Thoracic and Vascular Sciences 2nd Chair of Internal Medicine University of Padua Medical School Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Bertini","sequence":"additional","affiliation":[{"name":"Department of Cardiologic, Thoracic and Vascular Sciences 2nd Chair of Internal Medicine University of Padua Medical School Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bon","sequence":"additional","affiliation":[{"name":"Department of Cardiologic, Thoracic and Vascular Sciences 2nd Chair of Internal Medicine University of Padua Medical School Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Campello","sequence":"additional","affiliation":[{"name":"Department of Cardiologic, Thoracic and Vascular Sciences 2nd Chair of Internal Medicine University of Padua Medical School Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Vadori","sequence":"additional","affiliation":[{"name":"CORIT (Consortium for Research in Organ Transplantation) Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Galli","sequence":"additional","affiliation":[{"name":"Laboratorio di Tecnologie della Riproduzione CIZ srl, Istituto Sperimentale Italiano Lazzaro Spallanzani Cremona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Gavasso","sequence":"additional","affiliation":[{"name":"Department of Cardiologic, Thoracic and Vascular Sciences 2nd Chair of Internal Medicine University of Padua Medical School Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark B.","family":"Nottle","sequence":"additional","affiliation":[{"name":"Research Centre for Reproductive Health &amp; Discipline of Obstetrics and Gynaecology School of Paediatrics and Reproductive Health University of Adelaide Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Cowan","sequence":"additional","affiliation":[{"name":"Immunology Research Centre St Vincent's Hospital Melbourne Vic Australia"},{"name":"Department of Medicine University of Melbourne Melbourne Vic Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Cozzi","sequence":"additional","affiliation":[{"name":"CORIT (Consortium for Research in Organ Transplantation) Padua Italy"},{"name":"University Hospital Padua Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Simioni","sequence":"additional","affiliation":[{"name":"Department of Cardiologic, Thoracic and Vascular Sciences 2nd Chair of Internal Medicine University of Padua Medical School Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,2,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOT.0b013e3283446c65"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1600-6143.2003.00349.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2257.2005.00681.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2010.07.016"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0995-964"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3089.2007.00417.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3089.2003.00060.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3089.2003.02014.x"},{"key":"e_1_2_9_10_1","first-page":"7","article-title":"Preliminary study in a life supporting pig to primate xenotransplantation model using GALT KO pigs transgenic for human CD39, CD55, CD59 and fucosyltransferase proteins [abstract]","volume":"16","author":"Cozzi E","year":"2009","journal-title":"Xenotransplantation"},{"key":"e_1_2_9_11_1","first-page":"15","article-title":"Long\u2010term survival of nonhuman primates receiving life\u2010supporting transgenic porcine kidney xenografts","volume":"70","author":"Cozzi E","year":"2000","journal-title":"Transplantation"},{"issue":"1","key":"e_1_2_9_12_1","first-page":"87","article-title":"A comparison of the technical principle of the roTEG coagulation analyser and conventional thrombelastographic system [abstract]","volume":"72","author":"Calatzis AN","year":"1996","journal-title":"Ann Hematol"},{"key":"e_1_2_9_13_1","first-page":"A83","article-title":"Evaluation the FIBTEG\u2010S reagent on the ROTEG [abstract]","volume":"24","author":"Lang T","year":"2004","journal-title":"H\u00e4mostaseologie"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1653469"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0b013e32832a76e1"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2011.05593.x"}],"container-title":["Xenotransplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fxen.12024","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/xen.12024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T15:20:59Z","timestamp":1700666459000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/xen.12024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,14]]},"references-count":15,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1111\/xen.12024"],"URL":"https:\/\/doi.org\/10.1111\/xen.12024","archive":["Portico"],"relation":{},"ISSN":["0908-665X","1399-3089"],"issn-type":[{"value":"0908-665X","type":"print"},{"value":"1399-3089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,14]]}}}