Coagulopathy in α-galactosyl transferase knockout pulmonary xenotransplants.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Bush, EL; Barbas, AS; Holzknecht, ZE; Byrne, GW; McGregor, CG; Parker, W; Davis, RD; Lin, SS

Published Date

  • January 2011

Published In

Volume / Issue

  • 18 / 1

Start / End Page

  • 6 - 13

PubMed ID

  • 21342283

Electronic International Standard Serial Number (EISSN)

  • 1399-3089

Digital Object Identifier (DOI)

  • 10.1111/j.1399-3089.2011.00621.x

Language

  • eng

Conference Location

  • Denmark