title: The Effects of Exogenous Administration of Human Coagulation Factors Following Pig-to-Baboon Liver Xenotransplantation.
abstract: We sought to determine the effects of exogenous administration of human coagulation factors following pig-to-baboon liver xenotransplantation (LXT) using GalT-KO swine donors. After LXT, baboons received no coagulation factors (historical control, n = 1), bolus administration of a human prothrombin concentrate complex (hPCC; 2.5 mL/kg, n = 2), continuous infusion of hPCC (1.0 mL/h, n = 1) or continuous infusion of human recombinant factor VIIa (1 µg/kg per hour, n = 3). The historical control recipient demonstrated persistent thrombocytopenia despite platelet administration after transplant, along with widespread thrombotic microangiopathy (TMA). In contrast, platelet levels were maintained in bolus hPCC recipients; however, these animals quickly developed large-vessel thrombosis and TMA, leading to graft failure with shortened survival. Recipients of continuous coagulation factor administration experienced either stabilization or an increase in their circulating platelets with escalating doses. Furthermore, transfusion requirements were decreased, and hepatic TMA was noticeably absent in recipients of continuous coagulation factor infusions compared with the historical control and bolus hPCC recipients. This effect was most profound with a continuous, escalating dose of factor VIIa. Further studies are warranted because this regimen may allow for prolonged survival following LXT.
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Navarro-Alvarez
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Shah
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Zhu
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ligocka
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Yeh
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Elias
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Rosales
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Colvin
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Cosimi
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Markmann
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hertl
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.affiliation: Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Vagefi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001779:Blood Coagulation Factors / Q000008:administration & dosage*; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D006085:Graft Survival; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D010215:Papio; D013552:Swine; D013556:Swine, Miniature; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D001779:Blood Coagulation Factors