Changes in markers of coagulation and fibrinolysis offer insights into pathophysiological aspects of preservation injury during normothermic liver perfusion
Jule Dingfelder1, Laurin Rauter1, Sertac Kacar1, Gerd Silberhumer2, Andreas Salat1, Zoltan Mathe1, Georg Györi1, Thomas Soliman1, Dagmar Kollmann1, Gabriela Berlakovich1.
1Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria; 2Department of General Surgery, Medical University of Vienna, Vienna, Austria
Background: The perfusate used in normothermic machine perfusion (NMP) is mainly composed of red packed blood cells and colloid solution and is therefore free from thrombocytes and coagulation factors. Our aim was to monitor changes in composition of coagulation factors during NMP and to investigate their association with liver function during NMP and after transplantation.
Methods: NMP has been performed on a heterogenous study group of 16 grafts that included 12 extended criteria donor livers. Factor V activity (FV), factor XIII activity (FXIII), van Willebrand factor activity (vWF), D-dimer, plasminogen-activator-inhibitor (PAI-1) and thrombocyte count in perfusate were assessed. Liver and bile duct biopsies were taken before and after perfusion and after reperfusion. Median follow-up after transplantation was 11 months (IQR: 6.4-12).
Results: NMP and assessment of 16 livers resulted in 10 livers that were successfully transplanted. Main reasons for decline included inability to clear lactate, low bile quality, or signs of fibrosis in the frozen section. Two livers presented with increased D-dimer levels during perfusion (8.7 µg/mL and 12.3 µg/mL vs. mean peak D-dimer of 3.7 µg/mL SD: 3.1). One liver was transplanted, the histological analysis of the bile duct biopsies taken before implantation showed sclerosing cholangitis. Additionally, vWF activity during perfusion of this liver was increased (13 % vs. mean peak vWF activity of 6.4% SD: 2.5). The recipient had to be treated with a stent for an anastomotic stricture. The second liver with elevated D-dimer was severely steatotic and the only liver out of the study group that did not produce bile and was therefore declined for transplantation. The graft additionally presented with high levels of PAI-1 (299 IU/mL vs. mean peak PAI-1 of 186 IU/mL SD: 155) and increased FXIII activity in perfusate (158 % vs. mean peak FXIII activity 45% SD: 49). PAI-1 was also elevated in another three livers during perfusion, of which one was discarded due to increasing lactate after initial clearing and high grade of steatosis (peak PAI-1 605 IU/mL). Both other livers were successfully transplanted, one of the two recipients later developed an anastomotic stricture. Each of the three cases with increased PAI-1 levels coincided with peaks in either thrombocyte count, bilirubin or FV activity.
Conclusion: Changes in perfusate composition of coagulation and fibrinolysis factors offer interesting new insights in pathophysiological aspects of preservation injury and might allow for additional graft assessment during longer courses of NMP. Prospective studies are needed to validate these initial findings.
right-click to download