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BACKGROUND: Increased systemic fibrinolytic activity can occur in liver transplant recipients after the donor graft is reperfused. However, it remains unclear whether this is related solely to tissue plasminogen activator (t-PA) levels or whether unique metabolic changes can alter t-PA activity and enhance fibrinolytic activity. We hypothesise that an increase in sensitivity to t-PA-mediated fibrinolysis (StF) following liver reperfusion is associated with specific metabolic abnormalities. MATERIALS AND METHODS: Liver transplant recipients had serial blood samples analysed with a modified thrombelastography assay using exogenous t-PA to measure sensitivity/resistance to fibrinolysis with the lysis 30 min after maximum clot strength (tLY30). Paired plasma samples were analysed with mass spectroscopy-based metabolomics. The tLY30 was correlated to metabolites using Spearman's rho. StF was defined as a tLY30 change of >8.5% from the anhepatic phase to 30 min after reperfusion based on the distribution of tLY30 in a healthy control population. RESULTS: StF occurred in 53% of patients. Cohorts had similar MELD scores (18 vs 16, p=0.876) and tLY30 at baseline (p=0.867) and anhepatic phase of surgery (p=0.463). Thirty min after reperfusion, the tLY30 was 73% in patient with StF vs 33% in those without StF 33% (p=0.006). StF was associated with increased red blood cell transfusions (p=0.035), during the first 2 hours of reperfusion. Nine metabolites demonstrated a correlation with tLY30 (p