Uncontrolled donation after circulatory death donors suffer cardiac arrest followed by unsuccessful resuscitation. Their livers have been successfully transplanted, though strict maintenance and selection criteria are necessary to avoid adverse outcomes, namely ischemic type biliary lesions. We previously demonstrated that uDCD liver recipients develop severe coagulopathy and fibrinolysis (Blasi 2016). Given the liver is the major source of clotting and fibrinolytic factors, we hypothesized that changes in gene expression may be detected in uDCD livers and provide a basis for abnormalities observed.

METHODS Cardiac arrest was witnessed and resuscitation attempts unsuccessful. Death was declared based on absence of cardiorespiratory activity during a 5-min no-touch period. Femoral vessels were cannulated to establish normothermic regional perfusion, which was run during evaluation and recovery. 32 samples were taken from 16 uDCD livers: “A” before cold preservation and “B” after reperfusion. Total RNA was extracted and analyzed using microarrays; results were confirmed using RT-PCR. Finally, 61 biopsies from 38 uDCD livers were evaluated by light microscopy to rule out fibrin microthrombi.

RESULTS Both before preservation and after reperfusion, uDCD livers had significantly upregulated expression of genes that provoke fibrinolysis and inhibit coagulation, including tissue plasminogen activator, urokinase plasminogen activator, urokinase plasminogen activator receptor, and thrombomodulin. There was also decreased expression of genes implicated in hemostasis (von Willebrand factor) and inhibition of fibrinolysis (alpha-2-macroglobulin):

On histology, no fibrin microthrombi were detected, even in cases that developed ITBL (13%).

CONCLUSION Changes in gene expression in uDCD livers help explain severe coagulopathy and fibrinolysis seen in recipients. Endogenous fibrinolysis is upregulated in these livers most at risk for ITBL, and clinical DCD protocols using TPA to help prevent ITBL should undergo critical appraisal.

CITATION INFORMATION: Hessheimer A., Vendrell M., Sabater D., Muñoz J., Blasi A., García-Valdecasas J., Ruíz A., Navasa M., Fondevila C. Changes in Graft Gene Expression Contribute to Coagulopathy in UDCD Liver Transplantation Am J Transplant. 2017;17 (suppl 3).

« Back to 2018 American Transplant Congress