Warfarin or low-molecular-weight heparin therapy does not prolong pig-to-primate cardiac xenograft function

Guerard W. Byrne, Johannes M. Schirmer, David N. Fass, Sumeet S. Teotia, Walter K. Kremers, Hui Xu, Bashoo Naziruddin, Henry D. Tazelaar, John S. Logan, Christopher G.A. McGregor

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Microvascular thrombosis is a prominent feature in cardiac delayed xenograft rejection (DXR). We investigated the impact of warfarin or low-molecular-weight heparin (LMWH) anti-coagulation on xenograft function using a heterotopic pig-to-primate model. Donor hearts were from CD46 transgenic pigs and baboon immunosuppression included tacrolimus, sirolimus, anti-CD20 and TPC, an α-galactosyl-polyethylene glycol conjugate. Three groups of animals were studied. Group 1 (n = 9) was treated with warfarin. Group 2 (n = 13) with LMWH and Group 3, received no anticoagulant drugs. The median duration of xenograft function was 20 days (range 3-62 days), 18 days (range 5-109 days) and 15 days (range 4-53 days) in Groups 1 to 3 respectively. Anti-coagulation achieved the targeted international normalized prothrombin ratio (INR) and anti-factor Xa levels consistent with effective in vivo therapy yet, no significant impact on median xenograft function was observed. At rejection, a similar histology of thrombosis and ischemia was apparent in each group and the levels of fibrin deposition and platelet thrombi in rejected tissue was the same. Anti-coagulation with warfarin or LMWH did not have a significant impact on the onset of DXR and microvascular thrombosis. However, a role for specific anticoagulant strategies to achieve long-term xenograft function cannot be excluded.

Original languageEnglish (US)
Pages (from-to)1011-1020
Number of pages10
JournalAmerican Journal of Transplantation
Volume5
Issue number5
DOIs
StatePublished - May 1 2005

Keywords

  • Antibody
  • Anticoagulation
  • Cardiac
  • Non-Gal
  • Thrombosis
  • Xenotransplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Byrne, G. W., Schirmer, J. M., Fass, D. N., Teotia, S. S., Kremers, W. K., Xu, H., Naziruddin, B., Tazelaar, H. D., Logan, J. S., & McGregor, C. G. A. (2005). Warfarin or low-molecular-weight heparin therapy does not prolong pig-to-primate cardiac xenograft function. American Journal of Transplantation, 5(5), 1011-1020. https://doi.org/10.1111/j.1600-6143.2005.00792.x