Thrombolytic Therapy in Liver Transplantation Using Grafts from Donation After Circulatory Death Donors

Abstract

The use of donation after circulatory death (DCD) grafts is associated with the occurrence of ischemic-type biliary lesions (ITBL) and results in high morbidity and graft loss. It has been postulated that vascular stasis during cardio-circulatory arrest leads to microvascular thrombus formation and that the viability of DCD livers may be improved through the application of fibrinolytic therapy.

In this chapter, we provide a review of the literature showing that the dying process primarily leads to a hyperfibrinolytic coagulation state profile, reflected by maximum clot lysis in thromboelastometry and the absence of microthrombi in histological sections of both the intrahepatic and extrahepatic bile ducts of human DCD donor livers and also in experimental DCD pig livers. Treatment with the fibrinolytic drug tissue plasminogen activator (tPA) did not improve biochemical, functional and histological parameters after experimental DCD liver transplantation but has shown to bear some risk of excessive post-reperfusion bleeding in the clinical setting. The success of tPA to prevent ITBL reported in retrospective series always incorporated a concomitant wider optimizing protocol, with multiple simultaneous changes, such as meticulous bile duct flushing, use of pre-mortem heparin and shortening of ischemic and hepatectomy times. As the beneficial effect of tPA was never demonstrated in a proper randomized trial, it is worth questioning whether expensive and potentially hazardous routine use of a thrombolytic agent to prevent ITBL is justified.