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Fibrinolysis during liver transplantation in humans: role of tissue- type
plasminogen activator
WH Dzik, CF Arkin, RL Jenkins and DC Stump
Department of Medicine, New England Deaconess Hospital, Boston, MA 02215.
Human liver transplantation is frequently associated with a coagulopathy
and bleeding diathesis developing during the anhepatic phase of surgery.
The hemostatic defect has been attributed in part to accelerated
fibrinolysis. In this study we evaluated changes in specific blood
fibrinolytic parameters occurring in eight adult patients undergoing
first-time orthotopic liver transplantation. Five of the eight patients
experienced moderate to severe systemic fibrinolysis as reflected by alpha
2-antiplasmin consumption and fibrinogen degradation with the concomitant
appearance of fibrin(ogen) degradation products. In association with these
changes, an increase in tissue-type plasminogen activator (t-PA) activity
and t-PA antigen levels was also observed. Fibrinolysis was most pronounced
during the anhepatic phase of surgery and decreased after revascularization
of the grafted liver. Three additional patients who underwent the same
procedure manifested much less evidence of systemic fibrinolytic activation
and had minimal elevation of t-PA antigen levels or activity.
Urokinase-type plasminogen activator levels, although elevated in three
patients, were disassociated from increased t-PA levels and concomitant
systemic fibrinolysis. The operative course of those patients developing
t-PA-associated fibrinolysis was characterized by shock, acidosis,
generalized bleeding, and a need for substantially greater blood product
support during surgery. These findings suggest that the observed
fibrinolytic defect is related to increased circulating plasma levels of
t-PA, presumably resulting from a combination of increased intravascular
release and decreased hepatic clearance of t-PA. These observations may
have implications for intraoperative therapy for the transplant-related
coagulopathy and its associated bleeding.
Volume 71,
Issue 4,
pp. 1090-1095,
04/01/1988
Copyright © 1988 by The American Society of Hematology
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