Protease activities, as well as plasminogen activators, contribute to the "lytic" state during orthotopic liver transplantation.

High levels of tissue plasminogen activator (t-PA) have been reported to be the main component of the high fibrinolytic activity measured in patients during orthotopic liver transplantation. However, a previous study of our group suggested that specific t-PA may not completely account for the massive fibrinolytic activities recorded. In the present study we investigated the fibrinolytic patterns in 10 consecutive liver cirrhosis patients undergoing OLT. Euglobulin fibrinolytic activity, measured either on physiologic (fibrin plates) or amidolytic substrates, increased as expected during anhepatic and reperfusion phases, but largely exceeded the specific activity of t-PA, as proved by quenching procedures using anti-t-PA antibodies. The presence of plasmin- and trypsin-like amidolytic activities was detected in native plasmas at the end of anhepatic and reperfusion phases, together with decreased levels of protease inhibitors, especially alpha 1 Antitrypsin. In conclusion, the hyperfibrinolytic pattern recorded in the central OLT phases is not only attributable to an increased t-PA concentration, and is better described as a complex "lytic" state also including the presence of free proteases (plasmin- and trypsin-like), with limited participation of u-PA. Although t-PA increase is probably the main mechanism of stimulation of the fibrinolytic system during OLT, actual and not just potential proteolytic activities can be found in this condition independent of the occurrence of major hemorrhagic complications.