Changes in the contact system during orthotopic liver transplantation with and without aprotinin.
The main cause of nonsurgical bleeding during orthotopic liver transplantation has been attributed to be hyperfibrinolysis due to high plasma levels of tissue plasminogen activator. The aim of this study was to investigate contact activation and its possible contribution to fibrinolysis during OLT with and without aprotinin. Aprotinin or placebo was given to 20 patients undergoing OLT as part of a randomized double-blind trial. Plasma samples were collected before, during, and after OLT. There were decreased preoperative levels of prekallikrein and factor XIIa (P < 0.05), with a trend for kallikrein and factor XIIa activity to increase during OLT peaking on reperfusion (P < 0.05). Kallikrein inhibition, C1 esterase inhibitor, and alpha-2-macroglobulin levels were normal before surgery, with low normal levels of antithrombin III and alpha-2-antiplasmin; these levels decreased during OLT with no specific change on reperfusion. In the aprotinin-treated group, kallikrein inhibition levels increased (P < 0.05) from preoperative mean (+/- SD) values of 101 +/- 47% to 154 +/- 42% and antiplasmin levels increased (P < 0.05) from 72 +/- 28% to 243 +/- 53% during the anhepatic phase, reflecting the effect of aprotinin. The antifibrinolytic effect of aprotinin was demonstrated by decreased levels of D-dimer on reperfusion (P < 0.05) and at the end of OLT (P < 0.001) in the aprotinin-treated group. We have shown that contact activation during OLT is minimal and that aprotinin does not alter the pattern of contact activation, but provides an antikallikrein effect.
Segal
H C
HC
Department Research Haematology, Harefield Hospital, Middlesex, UK.
Hunt
B J
BJ
Cottam
S
S
Beard
C
C
Francis
J L
JL
Potter
D
D
Tan
K C
KC
D000328:Adult; D007611:Aprotinin / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects*; D016063:Blood Loss, Surgical / Q000503:physiopathology / Q000517:prevention & control*; D002648:Child; D003174:Complement C1 Inactivator Proteins / Q000032:analysis; D003173:Complement C1s / Q000032:analysis; D004311:Double-Blind Method; D015956:Factor XIIa / Q000032:analysis* / Q000037:antagonists & inhibitors; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007610:Kallikreins / Q000032:analysis / Q000037:antagonists & inhibitors; D016031:Liver Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D000511:alpha-Macroglobulins / Q000032:analysis
D003174:Complement C1 Inactivator Proteins; D000511:alpha-Macroglobulins; D007611:Aprotinin; D007610:Kallikreins; D015956:Factor XIIa; D003173:Complement C1s