Coagulopathy in α-galactosyl transferase knockout pulmonary xenotransplants

Errol Bush, Andrew S. Barbas, Zoie E. Holzknecht, Guerard W. Byrne, Christopher G. McGregor, William Parker, R. Duane Davis, Shu S. Lin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)6-13
Number of pages8
JournalXenotransplantation
Volume18
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Fingerprint

Transferases
Heterologous Transplantation
Swine
Lung
Transplants
Reperfusion
CD55 Antigens
Galactosyltransferases
Papio
Heterografts
Thrombocytopenia
Fibrinogen
Primates
Complement System Proteins
Transplantation
Macrophages
Gene Expression

Keywords

  • 1,3-galactosyltransferase
  • baboon
  • coagulopathy
  • macrophage
  • porcine
  • pre-clinical
  • pulmonary
  • xenotransplant

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Bush, E., Barbas, A. S., Holzknecht, Z. E., Byrne, G. W., McGregor, C. G., Parker, W., ... Lin, S. S. (2011). Coagulopathy in α-galactosyl transferase knockout pulmonary xenotransplants. Xenotransplantation, 18(1), 6-13. https://doi.org/10.1111/j.1399-3089.2011.00621.x

Coagulopathy in α-galactosyl transferase knockout pulmonary xenotransplants. / Bush, Errol; Barbas, Andrew S.; Holzknecht, Zoie E.; Byrne, Guerard W.; McGregor, Christopher G.; Parker, William; Davis, R. Duane; Lin, Shu S.

In: Xenotransplantation, Vol. 18, No. 1, 01.2011, p. 6-13.

Research output: Contribution to journalArticle

Bush, E, Barbas, AS, Holzknecht, ZE, Byrne, GW, McGregor, CG, Parker, W, Davis, RD & Lin, SS 2011, 'Coagulopathy in α-galactosyl transferase knockout pulmonary xenotransplants', Xenotransplantation, vol. 18, no. 1, pp. 6-13. https://doi.org/10.1111/j.1399-3089.2011.00621.x
Bush, Errol ; Barbas, Andrew S. ; Holzknecht, Zoie E. ; Byrne, Guerard W. ; McGregor, Christopher G. ; Parker, William ; Davis, R. Duane ; Lin, Shu S. / Coagulopathy in α-galactosyl transferase knockout pulmonary xenotransplants. In: Xenotransplantation. 2011 ; Vol. 18, No. 1. pp. 6-13.
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