Molecular incompatibilities in hemostasis between swine and men--impact on xenografting.
The rejection of xenografts is associated with vascular-based inflammation, thrombocytopenia and the consumption of coagulation factors that may evolve into disseminated intravascular coagulation. Natural regulators of coagulation in porcine xenografts have abnormal physiological interaction with human effectors. We have demonstrated the enhanced potential of porcine von Willebrand factor to associate with human platelet GPlb to be dependent upon the isolated AI domain of von Willebrand factor. The inability of porcine tissue factor pathway inhibitor (TFPI) to adequately neutralize human factor Xa (FXa), the aberrant activation of both human prothrombin and FXa by porcine EC and the failure of the porcine natural anticoagulant, thrombomodulin to bind human thrombin and hence activate human protein C may all be pathogenetic in the DIC following xenograft rejection. In this brief review, molecular incompatibilities of contributors in the physiologically fine tuned system of hemostasis are summarized and brought in context with the disordered thromboregulation, that seems to be invariably associated with delayed xenograft rejection. Possible therapeutic interventions are discussed.
Schulte am Esch
J
J
Department of Hepatobiliary and Transplantation Surgery, Clinic of Surgery, University Hospital, University of Hamburg, Germany. jschulte@uke.uni-hamburg.de
Rogiers
X
X
Robson
S C
SC
D000818:Animals; D004730:Endothelium, Vascular / Q000503:physiopathology; D005170:Factor X / Q000502:physiology; D006084:Graft Rejection / Q000097:blood / Q000209:etiology / Q000276:immunology; D006487:Hemostasis; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D015539:Platelet Activation; D011486:Protein C / Q000502:physiology; D011516:Prothrombin / Q000502:physiology; D013045:Species Specificity; D013552:Swine / Q000097:blood* / Q000276:immunology; D018180:Thrombomodulin / Q000097:blood; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D014183:Transplantation, Heterologous / Q000009:adverse effects* / Q000276:immunology*; D014841:von Willebrand Factor / Q000502:physiology
D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D018180:Thrombomodulin; C051928:lipoprotein-associated coagulation inhibitor; D014841:von Willebrand Factor; D011516:Prothrombin; D005170:Factor X