Studies on coagulation incompatibilities for xenotransplantation

Methods in Molecular Biology
Cristiana BulatoPaolo Simioni

Abstract

Microvascular thrombosis, following the activation of clotting cascade, is a hallmark of porcine solid organ xenograft rejection. The analysis of differences between human, monkey, and pig coagulation systems is crucial when monkey is used as animal model and pig as organ donor in xenotransplantation. Thrombosis, according to many authors, may be due to the molecular incompatibilities between natural anticoagulants present on pig endothelium and primate activated coagulation factors. The generation of activated protein C (PC) is critical for the physiological anticoagulation. One of the major incompatibilities may be related to the inability of pig thrombomodulin (TM) and endothelial protein C receptor to activate the recipient (primate) circulating PC in the presence of thrombin. Tissue factor pathway inhibitor (TFPI), is the primary inhibitor of tissue factor (TF)-induced coagulation. TFPI directly inhibits the activated factor X (FXa) and blocks the procoagulant activity of the TF/factor VIIa (FVIIa) complex by forming a quaternary TF/FVIIa/FXa/TFPI complex. Microvascular thrombosis, observed in the organ transplant, may also be due to the failure of pig TFPI to bind human FXa efficiently and inhibit human FVIIa/TF activity....Continue Reading

Citations

Jul 18, 2016·Journal of Veterinary Diagnostic Investigation : Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc·Aleksandra Pliszczak-KrólStanisław Graczyk
Mar 15, 2013·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Miroslaw JanowskiPiotr Walczak
Mar 13, 2014·Transplant International : Official Journal of the European Society for Organ Transplantation·Céline GleizesFlorence Toti
Sep 19, 2015·Tissue Antigens·M Vadori, E Cozzi
Jan 8, 2021·International Journal of Immunogenetics·Marco Carvalho-OliveiraConstanca Figueiredo

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