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Controlling coagulation dysregulation in xenotransplantation

Cowan, Peter Ja,b; Robson, Simon Cc; d'Apice, Anthony JFa,b

Current Opinion in Organ Transplantation: April 2011 - Volume 16 - Issue 2 - p 214–221
doi: 10.1097/MOT.0b013e3283446c65
Xenotransplantation: Edited by Jean-Paul Soulillou
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Purpose of review Deletion of the α1,3-galactosyltransferase (GalT) gene in pigs has removed a major xenoantigen but has not eliminated the problem of dysregulated coagulation and vascular injury. Rejecting GalT knockout organ xenografts almost invariably show evidence of thrombosis and platelet sequestration, and primate recipients frequently develop consumptive coagulopathy. This review examines recent findings that illuminate potential mechanisms of this current barrier to successful xenotransplantation.

Recent findings The coagulation response to xenotransplantation differs depending on the type of organ and quite likely the distinct vasculatures. Renal xenografts appear more likely to initiate consumptive coagulopathy than cardiac xenografts, possibly reflecting differential transcriptional responses. Liver xenografts induce rapid and profound thrombocytopenia resulting in recipient death within days due to bleeding; ex-vivo data suggest that liver endothelial cells and hepatocytes are responsible for platelet consumption by a coagulation-independent process.

It has been proposed that expression of recipient tissue factor on platelets and monocytes is an important trigger of consumptive coagulopathy. Finally, pigs transgenic for human anticoagulants and antithrombotics are slowly but surely coming on line, but have not yet been rigorously tested to date.

Summary Successful control of coagulation dysregulation in xenotransplantation may require different combinatorial pharmacological and genetic strategies for different organs.

aImmunology Research Centre, St Vincent's Hospital, Australia

bDepartment of Medicine, University of Melbourne, Melbourne, Victoria, Australia

cTransplant Institute and Liver Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

Correspondence to Professor Peter J. Cowan, Immunology Research Centre, St Vincent's Hospital Melbourne, PO Box 2900, Fitzroy, Melbourne, VIC 3065, Australia Tel: +61 3 9288 3140; fax: +61 3 9288 3151; e-mail: peter.cowan@svhm.org.au

© 2011 Lippincott Williams & Wilkins, Inc.