Contribution of cytokines to hyperfibrinolysis during orthotopic liver transplantation and effect of aprotinin

Abstract

A release of inflammatory mediators seems to take place during orthotopic liver transplantation (OLT), which may contribute to the hemostatic abnormalities observed in the reperfusion phase. We investigated 36 patients who underwent their first OLT. The first 10 patients received conventional supportive therapy and the remainder were treated with 400.000 KIH/h of aprotinin, from the beginning of surgery until skin closure. Blood samples were taken before surgery, during the preanhepatic, anhepatic, and reperfusion phases, and daily until the 5th postoperative day to determine tumor necrosis factor (TNF-α), interleukin 6 (IL-6), plasmin-antiplasmin (PAP) complexes, and fibrin degradation products (FbDP). Levels of both cytokines remained unchanged during the preanhepatic phase and increased significantly with the revascularization of the graft liver (P < 0.001) to normalize on postoperative day 3. A hyperfibrinolytic state, as assessed by increased PAP and FbDP, was also observed, starting during the anhepatic phase and reaching maximum expression after reperfusion (P < 0.001). The plasma levels of TNF, IL-6, and FbDP followed a similar pattern along surgery with maximum values during reperfusion. This suggested that cytokines may partially contribute to hyperfibrinolysis during OLT. Aprotinin treatment reduced PAP and FbDP generation (P < 0.01) without influencing the cytokine levels.