Normothermic Machine-perfused Human Donor Livers Produce Functional Hemostatic Proteins

Silke B Bodewes; Bianca Lascaris; Jelle Adelmeijer; Vincent E de Meijer; Robert J Porte; Ton Lisman

doi:10.1097/TP.0000000000004670

Normothermic Machine-perfused Human Donor Livers Produce Functional Hemostatic Proteins

Transplantation. 2023 Nov 1;107(11):2377-2383. doi: 10.1097/TP.0000000000004670. Epub 2023 Oct 21.

Authors

Silke B Bodewes^{1

2}, Bianca Lascaris^{1

2}, Jelle Adelmeijer¹, Vincent E de Meijer², Robert J Porte¹, Ton Lisman^{1

2}

Affiliations

¹ Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
² Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

PMID: 37291723
DOI: 10.1097/TP.0000000000004670

Abstract

Background: Normothermic machine perfusion (NMP) is used for the viability assessment of high-risk donor livers before transplantation. The production of hemostatic proteins is one of the major synthetic functions of the liver. The objective of this study was to measure the concentration and functionality of hemostatic proteins concentration in the NMP perfusate of human donor livers.

Methods: Thirty-six livers that underwent NMP for viability assessment were included in this study. Perfusate samples taken during NMP (start, 150 min, and 300 min) were used for the measurement of antigen and activity levels of hemostatic proteins (factors II, VII, and X; fibrinogen; plasminogen; antithrombin; tissue plasminogen activator; von Willebrand factor; and proteins induced by vitamin K absence). The antigen levels were correlated with hepatocellular function according to previously proposed individual hepatocellular viability criteria: lactate clearance and perfusate pH.

Results: Antigen levels of hemostatic proteins reached subphysiological levels in the NMP perfusate. Hemostatic proteins that were produced during NMP were at least partially active. All livers produced all hemostatic proteins tested within 150 min of NMP. Hemostatic protein concentrations did not significantly correlate with perfusate lactate and perfusate pH after 150 min of NMP.

Conclusions: All livers produce functional hemostatic proteins during NMP. The generation of a functional hemostatic system in NMP perfusate confirms the need for adequate anticoagulation of the perfusate to avoid generation of (micro)thrombi that may harm the graft.