MEDIATORS OF LEUKOCYTE ACTIVATION PLAY A ROLE IN DISSEMINATED INTRAVASCULAR COAGULATION DURING ORTHOTOPIC LIVER-TRANSPLANTATION

Leukocytes play an important role in the development of disseminated i ntravascular coagulation (DIC). In the reperfusion phase of OLT a DIC- Like situation has been described and has been held responsible for th e high blood loss during this phase. We investigated the role of leuko cytes in the pathogenesis of DIC in OLT by measuring the leukocytic me diators released upon activation (cathepsin B, elastase, TNF neopterin ) and the levels of thrombin-antithrombin III (TAT) complexes, seen as markers of prothrombin activation. Arterial blood samples were taken at 10 different time points during and after OLT. Samples were also ta ken of the perfusate released from the liver graft vein during the flu shing procedure before the reperfusion phase. Aprotinin was given as a continuous infusion (0.2-0.4 Mill. (KIU/hr) and its plasma levels wer e determined. Significantly elevated levels of neopterin (15-fold; P<0 .01), cathepsin B (440-fold;P<0.01) in the perfusate, as compared with the systemic circulation, as well as their significant increases in t he early reperfusion phase suggested that they were released by the gr aft liver. This was paralleled by elevated levels of elastase (1.3-fol d, P<0.05), TNF (1.5-fold, P=NS), and TAT complexes (1.4-fold; P<0.1) in the perfusate. Significant correlations could be identified between the parameters of leukocyte activation and TAT complexes, whereas no correlation was observed between any of the parameters investigated an d the aprotinin levels. Our results strongly indicate a release of leu kocytic mediators from the graft liver during its reperfusion which se ems to be related to the parallely increased prothrombin activation. N o correlation could be seen between levels of aprotinin and levels of leukocytic mediators.