title: Effects of long-term administration of high-dose recombinant human antithrombin in immunosuppressed primate recipients of porcine xenografts.
abstract: BACKGROUND
  Fibrin deposition is central to the acute humoral rejection process occurring in the presence of consumptive coagulopathy when pig organs are transplanted into primates.
  
  
  METHODS
  To assess whether strategies aimed at preventing fibrin formation may extend xenograft survival, we administered high daily doses of recombinant human antithrombin (rhAT) (500 U/kg twice daily) to obtain both anticoagulant and anti-inflammatory effects in immunosuppressed primate recipients of porcine kidneys.
  
  
  RESULTS
  Some degree of consumptive coagulopathy developed in both rhAT-treated (n=3) and untreated (n=3) primates. No major differences in the coagulation parameters analyzed were observed between the 2 groups. Similarly, no difference in survival was seen between rhAT-treated (20.6+/-4 days; range: 15-23 days) and untreated animals (17.3+/-11.6 days; range: 7-30 days), although the rhAT-treated primates had a higher bleeding tendency. Despite the high daily dose of rhAT, considerable fibrin deposition was observed in the graft as early as 2 weeks after transplantation.
  
  
  CONCLUSIONS
  These results suggest that a high daily dose of rhAT fails to influence survival or prevent fibrin formation and deposition in the graft in our pig-to-primate model. However, the potential role of rhAT administered in combination with heparins or other clotting inhibitor concentrates in this model remains to be determined.
authors.affiliation: Direzione Sanitaria, Padua General Hospital, Padua, Italy. Emanuele.cozzi@umpd.it
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cozzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Simioni
authors.forename: Massimo
authors.initials: M
authors.lastname: Boldrin
authors.forename: Michela
authors.initials: M
authors.lastname: Seveso
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldan
authors.forename: Roberto
authors.initials: R
authors.lastname: Busetto
authors.forename: Daniela
authors.initials: D
authors.lastname: Tormene
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gavasso
authors.forename: Massimo
authors.initials: M
authors.lastname: Castagnaro
authors.forename: Yann
authors.initials: Y
authors.lastname: Echelard
authors.forename: Tim
authors.initials: T
authors.lastname: Rice
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Paolo
authors.initials: P
authors.lastname: Carraro
authors.forename: Erika
authors.initials: E
authors.lastname: Bosio
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Valente
authors.forename: Antonio
authors.initials: A
authors.lastname: Pagnan
authors.forename: Gaetano
authors.initials: G
authors.lastname: Thiene
authors.forename: Ermanno
authors.initials: E
authors.lastname: Ancona
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000991:Antithrombins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005337:Fibrin / Q000037:antagonists & inhibitors; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D016030:Kidney Transplantation / Q000379:methods* / Q000473:pathology; D008252:Macaca fascicularis; D010314:Partial Thromboplastin Time; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology
chemical_list: D000991:Antithrombins; D011486:Protein C; D017293:Protein S; D011994:Recombinant Proteins; D005337:Fibrin