Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model

Abstract

Ischemic-type biliary lesions (ITBLs) arise most frequently after donation after circulatory death (DCD) liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug tissue plasminogen activator (TPA) as means to improve DCD liver graft quality and potentially avoid ITBL. Donor pigs were subjected to 1 hour of cardiac arrest (CA) and divided among 3 groups: no pre-arrest heparinization nor TPA during postmortem regional perfusion; no pre-arrest heparinization but TPA given during regional perfusion; and pre-arrest heparinization but no TPA during regional perfusion. In liver tissue sampled 1 hour after CA, fibrin deposition was not detected, even when heparin was not given prior to arrest. Although it was not useful to prevent microvascular clot formation, pre-arrest heparin did offer cytoprotective effects during CA and beyond, reflected in improved flows during regional perfusion and better biochemical, functional, and histological parameters during posttransplantation follow-up. In conclusion, this study demonstrates the lack of impact of TPA use in porcine DCD liver transplantation and adds to the controversy over whether the use of TPA in human DCD liver transplantation really offers any protective effect. On the other hand, when it is administered prior to CA, heparin does offer anti-inflammatory and other cytoprotective effects that help improve DCD liver graft quality. Liver Transplantation 24 665-676 2018 AASLD.

Heterotopic vascularization and functionalization of implantable bio engineered hepatic tissue alleviates liver injury in rats

“…We showed that our bioengineered hepatic tissue was ectopically expanded more than 400‐fold and self‐organized into vascularized liver structures that were actively functional. Moreover heparin has been shown to inhibit immune cell infiltration and prolong graft survival . In our study, we also showed that heparin offered anti‐inflammatory capacity (less immune cell infiltration) and conferred a cytoprotective effect (fewer apoptotic cells) to help the bioengineered hepatic tissue survive.…”

Expanding the Donor Pool With the Use of Extended Criteria Donation After Circulatory Death Livers

“…Interventions include, for example, the use of thrombolytics in the donor or recipient, normothermic perfusion after procurement, and use of extracorporeal membrane oxygenation after cardiac arrest . Additional modifiable recipient risk factors include the following: Hepatectomy time. Recipient WIT. CIT. …”

“…(8,9,24) The modifiable donor risk factors are as follows: Interventions include, for example, the use of thrombolytics in the donor or recipient, normothermic perfusion after procurement, and use of extracorporeal membrane oxygenation after cardiac arrest. (8,9,13,(25)(26)(27)(28)(29) Additional modifiable recipient risk factors include the following (30)(31)(32) :…”

A cost analysis of early biliary strictures following orthotopic liver transplantation in the United States

“…Our previous work has shown that routine use of tPA in the setting of DCD transplant may be one cost‐effective strategy for prevention of NAS in this particularly susceptible population . Recently, however, other studies have called into question the role of microthrombi in biliary stricture development after DCD transplantation as well as the utility of tPA in reducing biliary stricture incidence DCD liver transplant recipients, pointing toward the need for a multi‐institution, randomized trial to more clearly assess the value of routine tPA use in DCD transplantation for prevention of biliary strictures …”