Coagulation Prevention During Ex-Situ Normothermic Machine Perfusion of Human Donor Livers Using a Heparinized Plasma Based Perfusion Fluid

Karangwa, S.A. (Shanice) (2015) Coagulation Prevention During Ex-Situ Normothermic Machine Perfusion of Human Donor Livers Using a Heparinized Plasma Based Perfusion Fluid. thesis, Medicine.

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Abstract

Introduction: Ex-situ normothermic machine perfusion (NMP) offers the possibility of viability testing of extended criteria donor (ECD) livers prior to transplantation. When using a plasma based fluid for NMP, heparin is required to avoid thrombi formation within the liver and perfusion circuit. However, little is known about the disappearance and effectivity of heparin during NMP of the liver. The main aim of this study was to investigate the anticoagulant effect of heparin as well as analyse the fibrinolytic state during NMP of human donor livers. Methods: Twelve ECD livers declined for transplantation underwent 6 hours of NMP following a median duration of 6.5 hr cold-storage. 20,000 IU heparin was added to the perfusion fluid (total volume 2230 ml) during priming of the perfusion device (Liver Assist). Perfusate samples were taken every 30 minutes and plasma was obtained after centrifugation. Liver viability was assessed based on bile production and livers were grouped as “good” functioning (≥30 g bile during 6 hr NMP) or “poor” functioning (<30 g bile during 6 hr NMP). Heparin plasma levels were determined using an anti-Xa assay whereas the concentration of prothrombin fragment F1+2 (as marker of coagulation activation), D-dimer, PAP complex (as a marker for fibrinolysis), tPA and PAI-1 were determined using an ELISA. Biopsies of the liver parenchyma taken before and after NMP were stained for fibrin to detect microthrombi in the vasculature. Results: A decline in heparin levels over 6 hours of NMP was seen in both good and poor functioning livers however this decline proved to be minimal and short-lived before maintaining stable concentrations. No increase in F1+2 or histological evidence of microthrombi was noted in either group at the end of perfusion. A significant increase in Ddimer and PAP complex however was noted particularly after 2 hours however these levels remained stable after this. Conclusion: Fibrinolysis occurs as fibrin present in the livers prior to machine perfusion is broken down resulting in elevated D-dimers. This evidently only occurs within the first 2 hours of NMP after which it decreases and the D-dimer concentration stabilises. Additionally, no significant coagulation activation occurs during 6 hours of NMP and therefore a single bolus administration of 20,000 IU of heparin to a perfusion volume of about 2 l is sufficient to avoid microthrombi formation during NMP of donor livers.

Item Type:	Thesis (Thesis)
Supervisor name:	Porte, Prof. R. J. MD and Lisman, Prof. J. A. PhD and Surgical Research Laboratory and Section of HPB Surgery and Liver Transplantation and University Medical Center Groningen
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:55
Last Modified:	25 Jun 2020 10:55
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1571

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