Schulte am Esch J, Rogiers X, Robson S C
Department of Hepatobiliary and Transplantation Surgery, Clinic of Surgery, University Hospital, University of Hamburg, Germany.
Ann Transplant. 2001;6(3):12-6.
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.
异种移植的排斥反应与基于血管的炎症、血小板减少以及凝血因子的消耗有关，这些情况可能发展为弥散性血管内凝血。猪异种移植中凝血的天然调节因子与人类效应器存在异常的生理相互作用。我们已经证明，猪血管性血友病因子与人类血小板糖蛋白Ib结合的增强潜力取决于血管性血友病因子分离出的A1结构域。猪组织因子途径抑制剂（TFPI）无法充分中和人类因子Xa（FXa），猪内皮细胞对人类凝血酶原和FXa的异常激活，以及猪天然抗凝剂血栓调节蛋白无法结合人类凝血酶从而激活人类蛋白C，这些都可能是异种移植排斥后弥散性血管内凝血的发病机制。在这篇简短的综述中，总结了生理上精细调节的止血系统中各因素的分子不相容性，并结合似乎总是与异种移植延迟排斥相关的紊乱血栓调节进行了阐述。还讨论了可能的治疗干预措施。
