INTRODUCTION: Derangements of coagulation, e.g. thrombotic microangiopathy (TM) and disseminated intravascular coagulation (DIC), limit the success of pig-to-baboon organ transplantation. Studies have investigated the coagulation profile in baboons post-xenotransplantation (XTx), but an extended coagulation profile of healthy baboons pre-XTx has not been reported. METHODS: Blood was drawn from nine healthy male baboons (approximate age 5 yr, mean weight 15 kg) that had not undergone any prior surgical or therapeutic procedures. An extended coagulation profile, consisting of markers of thrombin activation, fibrinolysis, endothelial activation, the protein C pathway, and overall reactive state, was investigated by a reference coagulation laboratory, using tests for human plasma. The mean value +/- SD was calculated for 18 parameters (analytes); values outside of the mean +/- 2 SD were excluded. Three baboons subsequently underwent transplantation with hearts from GT-KO pigs, and received either no therapy (B24603), CVF (B25003), or CVF + leflunomide (B24903), and their extended coagulation parameters were followed. RESULTS: For 14 of the 18 analytes, the human reference range reflected the coagulation status of healthy baboons. Exceptions included thrombin/antithrombin complex and fibrinopeptide A, which were elevated compared with the human reference range, while plasminogen activity was lower. The human assay failed to detect baboon plasminogen activator inhibitor-1. Immediately after GT-KO pig heart transplantation, the untreated B24603 demonstrated a coagulation profile consistent with its postoperative clinical status; DIC was not apparent, and the heart was electively excised within 2.5 h. In B25003 and B24903, that rejected their grafts on days 8 and 12, respectively, the coagulation profile showed evidence of DIC, particularly in B24903, which was clinically coagulopathic by this time. CONCLUSIONS: (i) The human reference range of extended coagulation parameters forms a basis for studies in baboons, with a few exceptions. (ii) Antibody-mediated rejection of GT-KO pig hearts in baboons can be associated with laboratory and clinical evidence of DIC.
INTRODUCTION: Derangements of coagulation, e.g. thrombotic microangiopathy (TM) and disseminated intravascular coagulation (DIC), limit the success of pig-to-baboon organ transplantation. Studies have investigated the coagulation profile in baboons post-xenotransplantation (XTx), but an extended coagulation profile of healthy baboons pre-XTx has not been reported. METHODS: Blood was drawn from nine healthy male baboons (approximate age 5 yr, mean weight 15 kg) that had not undergone any prior surgical or therapeutic procedures. An extended coagulation profile, consisting of markers of thrombin activation, fibrinolysis, endothelial activation, the protein C pathway, and overall reactive state, was investigated by a reference coagulation laboratory, using tests for human plasma. The mean value +/- SD was calculated for 18 parameters (analytes); values outside of the mean +/- 2 SD were excluded. Three baboons subsequently underwent transplantation with hearts from GT-KO pigs, and received either no therapy (B24603), CVF (B25003), or CVF + leflunomide (B24903), and their extended coagulation parameters were followed. RESULTS: For 14 of the 18 analytes, the human reference range reflected the coagulation status of healthy baboons. Exceptions included thrombin/antithrombin complex and fibrinopeptide A, which were elevated compared with the human reference range, while plasminogen activity was lower. The human assay failed to detect baboon plasminogen activator inhibitor-1. Immediately after GT-KO pig heart transplantation, the untreated B24603 demonstrated a coagulation profile consistent with its postoperative clinical status; DIC was not apparent, and the heart was electively excised within 2.5 h. In B25003 and B24903, that rejected their grafts on days 8 and 12, respectively, the coagulation profile showed evidence of DIC, particularly in B24903, which was clinically coagulopathic by this time. CONCLUSIONS: (i) The human reference range of extended coagulation parameters forms a basis for studies in baboons, with a few exceptions. (ii) Antibody-mediated rejection of GT-KO pig hearts in baboons can be associated with laboratory and clinical evidence of DIC.
Authors: Burcin Ekser; John Bianchi; Suyapa Ball; Hayato Iwase; Anneke Walters; Mohamed Ezzelarab; Massimiliano Veroux; Bruno Gridelli; Robert Wagner; David Ayares; David K C Cooper Journal: Xenotransplantation Date: 2012-11-12 Impact factor: 3.907
Authors: Burcin Ekser; Gabriel J Echeverri; Andrea Cortese Hassett; Mark H Yazer; Cassandra Long; Michael Meyer; Mohamed Ezzelarab; Chih Che Lin; Hidetaka Hara; Dirk J van der Windt; Eefje M Dons; Carol Phelps; David Ayares; David K C Cooper; Bruno Gridelli Journal: Transplantation Date: 2010-09-15 Impact factor: 4.939
Authors: Burcin Ekser; Chih C Lin; Cassandra Long; Gabriel J Echeverri; Hidetaka Hara; Mohamed Ezzelarab; Vladimir Y Bogdanov; Donna B Stolz; Keiichi Enjyoji; Simon C Robson; David Ayares; Anthony Dorling; David K C Cooper; Bruno Gridelli Journal: Transpl Int Date: 2012-05-30 Impact factor: 3.782
Authors: Mohamed B Ezzelarab; Burcin Ekser; Agnes Azimzadeh; Chih Che Lin; Yuming Zhao; Rachael Rodriguez; Gabriel J Echeverri; Hayato Iwase; Cassandra Long; Hidetaka Hara; David Ayares; Richard N Pierson; Angus W Thomson; David K Cooper Journal: Xenotransplantation Date: 2014-09-11 Impact factor: 3.907
Authors: Hayato Iwase; Burcin Ekser; Hidetaka Hara; Carol Phelps; David Ayares; David K C Cooper; Mohamed B Ezzelarab Journal: Xenotransplantation Date: 2013-11-05 Impact factor: 3.907
Authors: Mohamed Ezzelarab; Bertha Garcia; Agnes Azimzadeh; Hongtao Sun; Chih Che Lin; Hidetaka Hara; Sean Kelishadi; Tianshu Zhang; Yih Jyh Lin; Hao-Chi Tai; Robert Wagner; Jnanesh Thacker; Noriko Murase; Kenneth McCurry; Rolf N Barth; David Ayares; Richard N Pierson; David K C Cooper Journal: Transplantation Date: 2009-03-27 Impact factor: 4.939