Coagulation in xenotransplantation

After xenogenic kidney transplantation or perfusion activation of porcine endothelial cells and of the recipients coagulation system can be observed. There are several factors contributing to this pathology including reperfusion injury, binding of xenoreactive natural antibodies, complement activation, secretion of TNF, activation of human blood cells, thrombocyte activation and incompatibilities of molecules regarding to control coagulation. To investigate the following processes after the contact of the human blood with the porcine endothelium we developed an ex vivo perfusion model where porcine kidneys were perfused with either porcine (autologous) or human (xenogenic) blood. During perfusion blood samples were collected and the coagulation parameters D Dimer, Thrombin‐antithrombin complexes (TAT), fibrinogen and antithrombin were measured. At the end of perfusion tissue samples were obtained for histological analyses and QPCR. The xenogenic perfusion experiments revealed a profound activation of the human blood coagulation shown by increase of D Dimer and TAT and decrease of fibrinogen and antithrombin. In addition, on histology could be multiple microthrombi observed. During the autologous perfusion, no signs of activation of the blood coagulation could be observed. The D dimer and TAT remained low and there was no consumption of fibrinogen and antithrombin. Assessment of endothelial cell activation showed a drastic increase of the activation markers VCAM‐1 and E‐Selectin only after xenogenic perfusion. Addition of the natural anticoagulant activated protein C abolished the derangement of coagulation and was able to reduce endothelial cell activation. To achieve normal haemostasis and endothelial cell function after xenotransplantation it is important to overcome the known molecular incompatibilities, to reliably prevent the derangement of coagulation and endothelial cell activation.