Thrombolytic protocol minimizes ischemic-type biliary complications in liver transplantation from donation after circulatory death donors.

Abstract

TO THE EDITOR: With interest, we have read the article by Seal et al.1 recently published in Liver Transplantation. The authors proposed that injection of tissue plasminogen activator, a potent thrombolytic agent, into the hepatic artery of donation after circulatory death (DCD) donor livers before transplantation reduces the incidence of biliary strictures after liver transplantation. We would like to challenge the basis for this potentially harmful therapy and wonder whether there is any evidence for the presence of thrombi in the biliary microcirculation of livers from DCD donors. At first sight, it seems reasonable to assume that clot formation may occur in the vasculature of a DCD donor because there is an inevitable period of circulatory arrest before cold flush out with preservation solution. However, in the study described by Seal et al.,1 all DCD donors received a therapeutic dose of heparin intravenously before withdrawal of life support, making it unlikely that clot formation may have occurred. Moreover, several studies have indicated that hypoxia due to circulatory arrest (as occurs in a dying person) is associated with a pronounced stimulation of the fibrinolytic system because of the release of endogenous plasminogen activators.2 In accordance with this, Vendrell et al.4 recently reported evidence of clinically relevant endogenous hyperfibrinolysis in DCD donors (Maastricht type II). These investigators, therefore, argued against the need for additional fibrinolytic therapy in DCD donors. Is there any evidence that despite full heparinization and the endogenous hyperfibrinolysis in DCD donors, relevant clot formation still occurs in the biliary microcirculation? To answer this question, we recently performed a histological study of biopsies taken from the extrahepatic bile duct of 128 donor livers at the time of transplantation.5 In 73 cases (23 DCD livers and 50 livers of donation after brain death [DBD] donors), bile duct biopsies were taken at the end of cold storage. In contrast to the study by Seal et al.,1 local legislation did not allow the administration of heparin to the donor before withdrawal of life support. Nevertheless, we found a very low (2.7%) incidence of thrombi in the peribiliary vascular plexus, and there was no difference between DCD and DBD livers (Table 1). This study, therefore, did not support the application of thrombolytic therapy in DCD donor livers. Table 1 - Presence of Thrombi in the Peribiliary Vascular Plexus (PVP) of Liver Grafts at the End of Cold Storage DBD Livers (n = 50) DCD Livers (n = 23) Total (n = 73) P Value Presence of thrombi in the PVP 1 (2.0%) 1 (4.3%) 2 (2.7%) 0.57 Altogether, we believe that other factors, such as increasing experience, may explain the observed differences in this retrospective study and that there is no proven scientific justification for the use of a thrombolytic agent in DCD liver transplantation.