Mechanism of coagulation dysfunction in the recipients mediated by tissue factor activation after liver xenotransplantation / 器官移植

ABSTRACT

Objective To investigate the mechanism underlying the activation of tissue factor (TF) that leads to coagulation dysfunction in the recipients after liver xenotransplantation. Methods Auxiliary heterotopic liver xenotransplantation was performed in 3 minipigs with α-1,3-galactosyltransferase gene-knockout (GTKO) as the donors and Tibetan macaque (Macaca thibetana) as the recipients. Postoperative coagulation function changes in the recipients were observed. Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining were adopted to quantitatively measure the expression levels of monkey and minipig TF messenger RNA (mRNA) and protein in the liver tissues of the primary and transplant livers at different time points before and after transplantation. The recalcification time of peripheral blood mononuclear cell (PBMC) was recorded in the normal control monkeys and the recipient monkeys before and 2 h after liver transplantation to evaluate the coagulation status in the recipients. Results All three recipients presented with different degrees of coagulation dysfunction after surgery, manifested as a decrease in fibrinogen level and a reduction in platelet count. The monkey TF protein was positively expressed in the primary livers after surgery, whereas negatively expressed in transplant livers before and after liver transplantation. The minipig TF protein was negatively expressed in both primary livers and transplant livers. At postoperative 2 h, monkey TF mRNA was up-regulated by (2.10±0.24) times in the primary liver compared with the preoperative level, whereas the minipig TF mRNA was up-regulated by (1.42±0.15) times compared with preoperative level. There was statistical significance between the primary livers and transplant livers (P=0.014). Compared with PBMC in the normal control monkeys and recipient monkeys before liver transplantation, the recalcification time of the PBMC in the recipient monkeys was significantly shortened at postoperative 2 h (both P<0.001). Conclusions At the presence of coagulation dysfunction after liver xenotransplantation, the level of TF activation in the primary livers is significantly higher than that in the transplant livers. The TF activation in the primary livers is the main cause of coagulation dysfunction after liver xenotransplantation.