Hemostasis and blood requirements in orthotopic liver transplantation with and without high-dose aprotinin

Several factors seem to lead to considerable bleeding and transfusion requirements during orthotopic liver transplantation (OLT) and postoperatively, but hyperfibrinolysis appears to be the most important factor. Aprotinin, a broad-spectrum serine protease inhibitor, has been shown to inhibit hyperfibrinolytic states.

A non-randomized, controlled clinical trial was performed to assess the efficacy of aprotinin in 20 consecutive OLT procedures (group A). The results obtained were compared with the findings in two groups of patients who did not receive aprotinin: one control group (C1) consisting of the 20 consecutive recipients who underwent OLT immediately prior to group A, and a second control group (C2) consisting of the 30 consecutive recipients undergoing OLT immediately after group A. Twenty-three hemostatic parameters were studied in group A and C1 and the blood product requirements were compared in all three group.

We observed a markedly reduced fibrinolysis in group A during the non-hepatic and reperfusion phases demonstrated by reduced tissue-type plasminogen activator (t-PA), alpha 2 antiplasmin-plasmin complex (APP) and D dimer levels and an increase in antiplasmin activity compared to C1 group (p < 0.05). In vitro experiments showed aprotinin to have an antiplasmin effect. The intraoperative transfusion of units of RBC and fresh frozen plasma (FFP) was significantly diminished in group A (8.1 and 16.7 U, respectively) when compared with groups C1 (20.4 and 36.0 U) and C2 (13.0 and 28.0 U) (p < 0.05); there was also a significantly greater number of patients not requiring intraoperative platelet transfusion in group A (p < 0.05). During the first 5 postoperative days, the number of patients in group A who did not require RBC transfusion was significantly larger than in groups C1 and C2 (p = 0.04).

In this study, the inhibition of fibrinolysis associated with the prophylaxis with aprotinin, administered in high doses by continuous intravenous infusion, appears to reduce the need for blood product transfusion during the OLT procedure.