title: Coagulopathy in α-galactosyl transferase knockout pulmonary xenotransplants.
abstract: BACKGROUND
  After substantial progress on many fronts, one of the remaining barriers still opposing the clinical application of xenotransplantation is a disseminated intravascular coagulopathy (DIC) that is observed in the pre-clinical model of porcine-to-primate transplantation. The onset of DIC is particularly rapid in recipients of pulmonary xenografts, usually occurring within the first days or even hours of reperfusion.
  
  
  METHODS
  In this study, we describe the results of two porcine-to-baboon transplants utilizing porcine lungs depleted of macrophages, deficient in the α-1,3-galactosyltransferase gene, and with the expression of human decay-accelerating factor, a complement regulatory protein.
  
  
  RESULTS
  In both cases, evidence of DIC was observed within 48 h of reperfusion, with thrombocytopenia and increases in levels of thrombin-antithrombin complex evident in both cases. Depletion of fibrinogen was observed in one graft, whereas elevation of D-dimer levels was observed in the other. One graft, which showed focal lymphocytic infiltrates pre-operatively, failed within 3 h.
  
  
  CONCLUSIONS
  The results indicate that further efforts to address the coagulopathy associated with pulmonary xenotransplantation are needed. Further, evidence suggests that resident porcine immune cells can play an important role in the coagulopathy associated with xenotransplantation.
authors.affiliation: Department of Surgery, Duke University, Durham, NC, USA.
authors.forename: Errol L
authors.initials: EL
authors.lastname: Bush
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Barbas
authors.forename: Zoie E
authors.initials: ZE
authors.lastname: Holzknecht
authors.forename: Guerard W
authors.initials: GW
authors.lastname: Byrne
authors.forename: Christopher G
authors.initials: CG
authors.lastname: McGregor
authors.forename: William
authors.initials: W
authors.lastname: Parker
authors.forename: R Duane
authors.initials: RD
authors.lastname: Davis
authors.forename: Shu S
authors.initials: SS
authors.lastname: Lin
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D001778:Blood Coagulation Disorders / Q000276:immunology*; D018958:CD55 Antigens / Q000235:genetics / Q000276:immunology; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005700:Galactosyltransferases / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006085:Graft Survival; D006801:Humans; D016040:Lung Transplantation / Q000276:immunology*; D010215:Papio / Q000276:immunology; D013552:Swine / Q000276:immunology; D013917:Thrombin / Q000378:metabolism; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology
chemical_list: D000991:Antithrombins; D018958:CD55 Antigens; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase; D013917:Thrombin