Authors: Ramackers, W.; Friedrich, L.; Tiede, A.; Schuettler, W.; Bergmann, S.; Broecker, V.; Schwinzer, R.; Winkler, M.

Source: Xenotransplantation, Volume 15, Number 5, September/October 2008 , pp. 303-303(1)

Publisher: Wiley-Blackwell

Abstract:

Following either discordant transplantation of porcine organs into primate recipients or after ex vivo perfusion of porcine organs with human blood, a profound activation of the primate/human blood coagulation can be observed. This activation may result in thrombotic microangiopathy and changes of coagulation resembling disseminated intravascular coagulation with subsequent death of the recipient animals. There are several factors contributing to this pathology including endothelial cell activation, activation of human blood cells, thrombocyte activation and incompatibilities of molecules regarding to control coagulation. Several potentially important molecular incompatibilities between the porcine and the primate coagulation system have been noted: The inability of porcine tissue factor pathway inhibitor (TFPI) to adequately neutralize human factor Xa (FXa), the aberrant activation of both human prothrombin and FX by porcine endothelial cells and the failure of the porcine natural anticoagulant thrombomodulin to activate the anti-coagulant human protein C. Normal hemostasis is a complex balance between pro- and antithrombotic pathways. These pathways are balanced by inhibitory systems including the heparin-antithrombin interaction, TFPI, the generation of activated protein C by a proper thrombomodulin/thrombin interaction and the fibrinolytic system. To achieve normal haemostasis after xenotransplantation it is important to overcome the known molecular incompatibilities (i.e. by transgenic organs) and to reliably prevent the derangement of coagulation.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1399-3089.2008.00488_11.x

Publication date: 2008-09-01

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• In this Subject: Microbiology ,  Surgery
• By this author: Ramackers, W. ;  Friedrich, L. ;  Tiede, A. ;  Schuettler, W. ;  Bergmann, S. ;  Broecker, V. ;  Schwinzer, R. ;  Winkler, M.

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