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Warfarin or low-molecular-weight heparin therapy does not prolong pig-to-primate cardiac xenograft function.
Am J Transplant
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.
|Title:||Warfarin or low-molecular-weight heparin therapy does not prolong pig-to-primate cardiac xenograft function.|
|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
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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