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

Byrne, GW; Schirmer, JM; Fass, DN; Teotia, SS; Kremers, WK; Xu, H; ... McGregor, CG; + view all (2005) Warfarin or low-molecular-weight heparin therapy does not prolong pig-to-primate cardiac xenograft function. Am J Transplant , 5 (5) 1011 - 1020. 10.1111/j.1600-6143.2005.00792.x.

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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 alpha-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 anti-coagulant 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 anti-coagulant strategies to achieve long-term xenograft function cannot be excluded.

Type:Article
Title:Warfarin or low-molecular-weight heparin therapy does not prolong pig-to-primate cardiac xenograft function.
Location:Denmark
DOI:10.1111/j.1600-6143.2005.00792.x
Language:English
Keywords:Animals, Animals, Genetically Modified, Anticoagulants, Antigens, CD, Antigens, CD46, Factor Xa, Heart Transplantation, Heparin, Low-Molecular-Weight, Immunoglobulin G, Immunoglobulin M, Immunosuppressive Agents, International Normalized Ratio, Ischemia, Membrane Glycoproteins, Microcirculation, Myocardium, Papio, Primates, Prothrombin, Sirolimus, Swine, Tacrolimus, Thrombosis, Time Factors, Transplantation, Heterologous, Treatment Outcome, Vitamin K, Warfarin
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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