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Potential factors influencing the development of thrombocytopenia and consumptive coagulopathy after genetically modified pig liver xenotransplantation
Author(s) -
Ekser Burcin,
Lin Chih C.,
Long Cassandra,
Echeverri Gabriel J.,
Hara Hidetaka,
Ezzelarab Mohamed,
Bogdanov Vladimir Y.,
Stolz Donna B.,
Enjyoji Keiichi,
Robson Simon C.,
Ayares David,
Dorling Anthony,
Cooper David K.C.,
Gridelli Bruno
Publication year - 2012
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2012.01506.x
Subject(s) - xenotransplantation , medicine , platelet , coagulopathy , immunology , tissue factor , peripheral blood mononuclear cell , consumptive coagulopathy , transplantation , liver transplantation , platelet activation , coagulation , biology , in vitro , biochemistry
Summary Upregulation of tissue factor (TF) expression on activated donor endothelial cells (ECs) triggered by the immune response (IR) has been considered the main initiator of consumptive coagulopathy (CC). In this study, we aimed to identify potential factors in the development of thrombocytopenia and CC after genetically engineered pig liver transplantation in baboons. Baboons received a liver from either an α1,3‐galactosyltransferase gene‐knockout (GTKO) pig ( n  = 1) or a GTKO pig transgenic for CD46 ( n  = 5) with immunosuppressive therapy. TF exposure on recipient platelets and peripheral blood mononuclear cell (PBMCs), activation of donor ECs, platelet and EC microparticles, and the IR were monitored. Profound thrombocytopenia and thrombin formation occurred within minutes of liver reperfusion. Within 2 h, circulating platelets and PBMCs expressed functional TF, with evidence of aggregation in the graft. Porcine ECs were negative for expression of P‐ and E‐selectin, CD106, and TF. The measurable IR was minimal, and the severity and rapidity of thrombocytopenia were not alleviated by prior manipulation of the IR. We suggest that the development of thrombocytopenia/CC may be associated with TF exposure on recipient platelets and PBMCs (but possibly not with activation of donor ECs). Recipient TF appears to initiate thrombocytopenia/CC by a mechanism that may be independent of the IR.

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