Controlling coagulation dysregulation in xenotransplantation
Peter J Cowan1, Simon C Robson, Anthony J F d'Apice
1Immunology Research Centre, St Vincent's Hospital, and Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia. peter.cowan@svhm.org.au
Current Opinion in Organ Transplantation
|March 19, 2011
Summary
Xenotransplantation faces challenges with coagulation and vascular injury, even after removing major antigens. Different organs require unique strategies to overcome these barriers for successful transplantation.
Area of Science:
- Transplantation immunology
- Vascular biology
- Coagulation science
Background:
- Deletion of the α1,3-galactosyltransferase (GalT) gene in pigs removes a major xenoantigen but does not resolve coagulation dysregulation and vascular injury.
- GalT knockout organ xenografts often exhibit thrombosis and platelet sequestration, with primate recipients developing consumptive coagulopathy.
Purpose of the Study:
- To review recent findings on the mechanisms underlying coagulation dysregulation in xenotransplantation.
- To identify barriers to successful xenotransplantation despite GalT gene deletion.
Main Methods:
- Review of recent scientific literature on xenotransplantation and coagulation.
- Analysis of organ-specific responses and potential triggers of coagulopathy.
Main Results:
- Coagulation response varies by organ type; renal xenografts may promote consumptive coagulopathy more than cardiac xenografts.
- Liver xenografts cause rapid thrombocytopenia and bleeding, potentially via a coagulation-independent process involving liver cells.
- Recipient tissue factor expression on platelets and monocytes may trigger coagulopathy.
Conclusions:
- Overcoming coagulation dysregulation in xenotransplantation necessitates organ-specific combinatorial strategies.
- Genetic modifications, such as pigs transgenic for human anticoagulants, are emerging but require further rigorous testing.
