Possible role of extracellularly released phagocytic proteinases in the coagulation disorder during liver transplantation

Orthotopic liver transplantation is frequently associated with a
complex coagulation disorder, influencing the outcome of the
procedure. In this respect, disseminated intravascular coagulation
(DIC) had been suggested to be of causative importance for bleeding
complications after reperfusion of the liver graft. In 10
consecutive patients undergoing orthotopic liver transplantations,
we studied the occurrence of two phagocyte proteinases of different
origin in the graft liver perfus-ate and in systemic blood during
the operation, as well as their effects on hemostasis. As compared
with plasma samples taken at the end of the anhepatic phase, highly
significant increases of cathepsin B and thrombin-anti-thrombin III
complexes (TAT), as well as highly significant decreases in
antithrombin III, protein C, and C1-inhibitor were observed in
graft liver perfusate. Von Willebrand factor and fibrinogen were
slightly decreased, whereas the elastase-alpha1 proteinase
inhibitor complexes (EPI) were elevated. In plasma the activity of
cathepsin B remained unchanged during the prereperfusion phases,
but immediately after revascularization of the graft this cysteine
proteinase increased. The EPI showed a gradual increase in plasma
during the preanhepatic and anhepatic phases but a more pronounced
increase in the reperfusion phase. In parallel with the rise in
these two proteinases TAT increased and the activities of
antithrombin III and C1-inhibitor in plasma decreased after
reperfusion. At 12 hr after revascularization plasma levels of TAT,
antithrombin III, and C1-inhibitor had returned to the
prereperfusion ranges, whereas cathepsin B and EPI were
significantly above the baseline levels. These observations are
consistent with the hypothesis that extracellularly released
lysosomal proteinases may play a role in the development of a
DIC-like constellation, including thrombin formation after
revascularization of the liver graft. For the first time we could
prove the occurrence of phagocyte proteinases in graft liver
perfusate and evaluate the importance of these proteinases for the
understanding of the pathophysiology leading to bleeding
complications in patients undergoing orthotopic liver
transplantation.