Production of Physiologically Relevant Quantities of Hemostatic Proteins During Normothermic Machine Perfusion of Human Livers

S.A. Karangwa, J. Adelmeijer, A.P.M. Matton, V.E.D.M. de Meijer, J.A. Lisman, R.J. Porte

Thursday 15 march 2018

11:50 - 12:00h at Van Rijck/Ruys Zaal

Categories: Clinical, Session (parallel)

Parallel session: Parallel session 5: Clinical

Background

Ex situ normothermic machine perfusion provides the opportunity to assess graft function and viability, particularly of sub-optimally functioning donor livers, prior to transplantation. During ex-situ NMP, donor livers usually resume normal metabolic and synthetic functions; such as hemostatic protein production. However, the quantities of these proteins produced are currently unknown.

Methods

Six donor livers declined for transplantation underwent 6 hours of end-ischemic NMP using a heparinized plasma-free perfusion fluid. Concentrations of key pro-hemostatic (Factors II, V, VII and X, fibrinogen and VWF), anti-coagulant (protein C and antithrombin III) and fibrinolytic (plasminogen and tissue-plasminogen activator) proteins were measured in perfusion fluid at regular intervals during NMP and compared with a plasma-based reference solution.

Results

Pro-coagulants showed an increase of 9-57% of the levels measured in the plasma reference solution whereas anticoagulant and fibrinolytic protein levels amounted to 41-71% and 18-116%, respectively.

Conclusion

This study demonstrates the capability of donor livers perfused with a plasma-free perfusion fluid to produce substantial amounts of pro-coagulant, anti-coagulant and fibrinolytic proteins during a relatively short period of NMP. These results are influential in determining appropriate anticoagulation protocols to avoid activation of hemostasis throughout NMP.