Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 882-896 |
| Number of pages | 15 |
| Journal | Transplant International |
| Volume | 25 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2012 |
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Keywords
- baboon
- consumptive coagulopathy
- genetically engineered
- liver transplantation
- pig
- tissue factor
- xenotransplantation
ASJC Scopus subject areas
- Transplantation
Cite this
Potential factors influencing the development of thrombocytopenia and consumptive coagulopathy after genetically modified pig liver xenotransplantation. / 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.
In: Transplant International, Vol. 25, No. 8, 08.2012, p. 882-896.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Potential factors influencing the development of thrombocytopenia and consumptive coagulopathy after genetically modified pig liver xenotransplantation
AU - Ekser, Burcin
AU - Lin, Chih C.
AU - Long, Cassandra
AU - Echeverri, Gabriel J.
AU - Hara, Hidetaka
AU - Ezzelarab, Mohamed
AU - Bogdanov, Vladimir Y.
AU - Stolz, Donna B.
AU - Enjyoji, Keiichi
AU - Robson, Simon C.
AU - Ayares, David
AU - Dorling, Anthony
AU - Cooper, David K C
AU - Gridelli, Bruno
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - baboon
KW - consumptive coagulopathy
KW - genetically engineered
KW - liver transplantation
KW - pig
KW - tissue factor
KW - xenotransplantation
UR - http://www.scopus.com/inward/record.url?scp=84863718470&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863718470&partnerID=8YFLogxK
U2 - 10.1111/j.1432-2277.2012.01506.x
DO - 10.1111/j.1432-2277.2012.01506.x
M3 - Article
VL - 25
SP - 882
EP - 896
JO - Transplant International
JF - Transplant International
SN - 0934-0874
IS - 8
ER -