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

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39 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

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Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

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