Activation of Fibrinolysis, But Not Coagulation, During End-ischemic Ex Situ Normothermic Machine Perfusion of Human Donor Livers.

Background: Ex situ normothermic machine perfusion (NMP) can be performed after traditional static cold preservation to assess graft function and viability prior to transplantation. It is unknown whether this results in activation of coagulation and fibrinolysis, as may occur upon graft reperfusion in vivo. Methods: Twelve donor livers declined for transplantation underwent 6 hours of end-ischemic NMP using a heparinized plasma-based perfusion fluid. Concentration of prothrombin fragment F1+2 (marker of coagulation activation), D-dimer, PAP complex, tPA and PAI-1 (markers for fibrinolysis) and alanine aminotransferase (ALT; marker of ischemia/reperfusion [I/R] injury) were measured in perfusion fluid at regular intervals. Liver biopsies were examined for the presence of fibrin, using light microscopy after MSB staining. Results: No significant increase in prothrombin F1+2 was noted during NMP. D-dimer and PAP complex levels increased soon after start of NMP and D-dimer concentrations correlated significantly with levels of tPA. In livers displaying good function during NMP, perfusate levels of ALT and D-dimers were low (3,500 ng/mL) were in found in livers with poor graft function. Activation of fibrinolysis correlated significantly with the degree of I/R injury, as reflected by ALT levels. Conclusion: End-ischemic ex situ NMP results in activation of fibrinolysis, but not of coagulation. Markers of fibrinolysis activation correlate significantly with markers of I/R injury. High concentrations of D-dimer early after start of NMP can be considered a marker of severe I/R injury and a predictor of poor liver graft function. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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