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TO THE EDITOR: Like many transplant centers, our early experience with donation after circulatory death (DCD) liver transplantation yielded high rates of biliary complications despite short cold ischemia times and administration of heparin antemortem in the donor. We recently reported a marked reduction in the rate of biliary complications in DCD liver transplants with routine administration of tissue plasminogen activator (tPA) in the early reperfusion period.1 The rationale for using thrombolytic agents in DCD liver transplantation was initially based on the hypothesis that the formation of microthrombi in the peribiliary vasculature during the circulatory arrest period of DCD organ recovery leads to ischemic stricture formation.2 In a letter to the editor, Burlage et al. offer several lines of evidence to challenge this hypothesis and question the benefits of tPA relative to the potential risks. The authors reference a recent study of DCD donors (Maastricht type II)3 and a review of trauma literature4 demonstrating hyperfibrinolysis in the setting of uncontrolled hemodynamic instability. However, a majority of DCD donors used for liver transplantation in the United States and Canada are from controlled circulatory arrest (Maastricht type III) and likely have a different coagulation profile. We caution against presuming a similar hyperfibrinolytic state exists in controlled DCD donors and are skeptical that it would provide significant protection against events leading to biliary stricture formation. In their recent report on the pathophysiology of bile duct injury, op den Dries et al.5 observed a very low incidence of microthrombi in the peribiliary vascular plexus from biopsies of the extrahepatic bile duct margin. The absence of microthrombi in the extrahepatic bile duct, however, does not exclude the presence of intrahepatic microthrombi that could precipitate the most clinically significant diffuse cholangiopathies. In a porcine model of DCD liver transplantation, we have consistently observed microthrombi in the peribiliary arteries of intrahepatic bile ducts only (Fig. 1; M. Selzner, unpublished data). In keeping with this observation, in our clinical study, we did not observe lower rates of extrahepatic strictures but rather a marked reduction in diffuse intrahepatic cholangiopathy. The presumed benefit of tPA is the elimination of intrahepatic microthrombi, improved organ perfusion,6 and reduction of ischemic events.Figure 1: Intrahepatic biopsy from porcine model of DCD liver transplantation before reperfusion. (left) Light microscopy (40×) demonstrating peribiliary vascular thrombosis and (right) electron microscopy demonstrating intravascular crosslinked fibrin.The successful use of DCD donors in liver transplantation is multifactorial, and the clinical practice of DCD liver transplantation will certainly evolve as our understanding of the pathophysiology grows. With the use of a tPA protocol at our centers, the risk of ischemic cholangiopathy in DCD liver transplants is equivalent to standard donors without significant adverse events or hemorrhage related to the use of tPA. Ultimately, we share the same objective of improving outcomes to safely and effectively use livers from DCD donors through continued monitoring of our own results, careful consideration of emerging basic science, and clinical research and incorporation of new innovations in transplantation (eg, ex vivo perfusion).

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