title: Fibrinolytic activity during orthotopic liver transplantation with and without aprotinin.
abstract: Hyperfibrinolysis during orthotopic liver transplantation (OLT) has been attributed to high plasma levels of tissue plasminogen activator (t-PA). This study investigated the contribution of urokinase plasminogen activator (u-PA) to hyperfibrinolysis and the effects of high-dose perioperative aprotinin (Trasylol) on fibrinolytic activation. Plasma samples were collected before, during, and after OLT in fifty five patients receiving either high dose aprotinin or placebo in a randomized double-blind trial. t-PA antigen and u-PA antigen and activity levels were increased preoperatively compared with normal controls (P < 0.05). Hyperfibrinolysis was seen during the anhepatic phase as shown by shortened euglobulin clot lysis times (ECLT) and an increase in D-dimer titers. t-PA levels peaked on reperfusion and fell at the end of the operation, and u-PA levels did not increase during OLT, but showed a decrease at the end of the operation. With aprotinin treatment, t-PA levels were lower on graft reperfusion than the placebo group (P < 0.05), but there was no difference in u-PA antigen or activity levels between groups. Fibrinolytic inhibition during OLT by aprotinin was demonstrated by prolonged ECLT (P < 0.05), reduced D-dimer levels (P < 0.05), and an increase in antiplasmin activity (P < 0.05). This study showed that the main antifibrinolytic action of aprotinin is as an antiplasmin agent with some effect on t-PA-but not u-PA-mediated fibrinolysis.
authors.affiliation: Department of Research Haematology, Harefield Hospital, Middlesex, United Kingdom.
authors.forename: H C
authors.initials: HC
authors.lastname: Segal
authors.forename: B J
authors.initials: BJ
authors.lastname: Hunt
authors.forename: S
authors.initials: S
authors.lastname: Cottam
authors.forename: A
authors.initials: A
authors.lastname: Downing
authors.forename: C
authors.initials: C
authors.lastname: Beard
authors.forename: J L
authors.initials: JL
authors.lastname: Francis
authors.forename: D
authors.initials: D
authors.lastname: Potter
authors.forename: K C
authors.initials: KC
authors.lastname: Tan
mesh_terms: D000328:Adult; D007611:Aprotinin / Q000097:blood / Q000494:pharmacology*; D001777:Blood Coagulation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016031:Liver Transplantation; D008875:Middle Aged; D012712:Serum Globulins / Q000378:metabolism; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood
chemical_list: D012712:Serum Globulins; D007611:Aprotinin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator