THROMBOSIS RESEARCH 63; 287-297,199l 0049-3848/91 $3.00 + .OO Printed in the USA. Copyright (c) 1991 Pergamon Press pk. All rights reserved.
THE USE OF HIGH DOSE APROTININ IN LIVER TRANSPLANTATION: THE INFLUENCE ON FIBRINOLYSIS AND BLOOD LOSS
H. Grosse’, W. Lobbes’, M. Frambach’, 0. von Broen’, B. Ringe2, and M. Barthels3 ‘Zentrum Anaesthesiologie Abt. I, 2Klinik fur Abdominal- und Transplantationschirurgie, ‘Abteilung Haematologie und Onkologie der Medizinischen Hochschule Hannover, Germany
(Received
10.11 .1990; accepted
in revised form 30.4.1991
by Editor H. Graeff)
ABSTRACT Orthotopic liver transplantation (OLT) is frequently associated with systemic fibrinogenolysis and diffuse bleeding. At present antifibrinolytic treatment has not been initiated routinely in OLT. Therefore the influence of high dose aprotinin in OLT (2 million kallikrein inactivator units (KIU) given after induction of anesthesia followed by a 500,000 KlUlh infusion throughout the operation) on intraoperative blood loss and fibrinolysis was studied in 25 patients compared to 25 patients without aprotinin. The incidence of fibrinolysis shown in thrombelastography was 72 O/O in the control group versus 16 % in the aprotinin group. Oozing after reperfusion of the graft caused by severe fibrinolysis defined as a clot lysis index below 15 % was only observed in the control group (42.8%). In contrast no significant difference was found between the groups in the course of fibrin and fibrinogen degradation product levels (FbDP, FgDP) afthough the mean concentrations of both parameters were evidently lower in the aprotinin treated patients. Levels of tissue-type plasminogen activator (tPA) activity were initially high in both groups and peaked during and after the anhepatic period. After aprotinin there was a trend of lower t-PA levels which reached significance at the time of reperfusion (p ~0.02). In both groups the course of thrombin antithrombin complex was in line with the variations of FbDP and FgDP. No correlation between thrombin formation and t-PA activity was found. Mean homologous blood requirement was reduced by 50 O/O (5.6 f4.G vs. 11.2 +8.6 units, p eO.005) The blood saving effect was more pronounced in the postanhepatic period (p 4 pts were considered as severe hemostatic impairment)(Tab. 1).
TABLE 1 Patient Data and Type of Operation
Age (years) Hematocrit (~01%) Coagulation score (points) Previous laparotomy (n) Cell Saver (n) Veno-venous bypass (n) Anhepatic time (min) Total operation time (min) Indications (n) Liver cirrhosis Acute hepatic failure Retransplantations Liver tumors Miscellaneous
Aprotinin group n = 25
Control group n = 25
41.7 f 13.4 28.2 f 3.1 5.8 ? 2.7 9 19 20 104.0 f 57.8 374.1 f 79.4
42.0 +12.9 27.8 + 4.4 5.2 + 2.9 7 21 20 83.0 + 23.4 375.9 + 80.1
12 2 3 3 5
13 3 3 4 2
Resutts of the fibrinolytic aa Preoperatively we found in the control group a state of enhanced fibrinolytic activity with reduced levels of plasminogen and a2-AP, moderatly elevated levels of t-PA and
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APROTININ IN LIVER TRANSPLANTATION
Vol. 63, No. 3
markedly increased concentrations of fibrin- as well as fibrinogen degradation products (A in Fg.1, 2). During the surgical procedure plasminogen showed minimal changes and increased towards the end of surgery. Levels of a2-AP remained below baseline values throughout the operation with a sighificant transient decline at time of graft recirculation. During the course of PAI- we found a continous drop from 14.9 fll.7 AU/l after induction of anesthesia to 1.6 f5.1 AU/l after recirculation of the graft (p ~0.00001). At that time PAI- activity was undectable in a number of patients. At the end of transplantation the mean levels were found above normal (22.4 f15.7 AU/l) (Fig. 1).
90
80
40
1
!?!G_.l Changes in plasminogen, a2-antiplasmin and plasminogen activator inhibitor-l in the control group. Meansf SD,differencesfromA statistically significant: p
THE USE OF HIGH DOSE APROTININ IN LIVER TRANSPLANTATION: THE INFLUENCE ON FIBRINOLYSIS AND BLOOD LOSS
H. Grosse’, W. Lobbes’, M. Frambach’, 0. von Broen’, B. Ringe2, and M. Barthels3 ‘Zentrum Anaesthesiologie Abt. I, 2Klinik fur Abdominal- und Transplantationschirurgie, ‘Abteilung Haematologie und Onkologie der Medizinischen Hochschule Hannover, Germany
(Received
10.11 .1990; accepted
in revised form 30.4.1991
by Editor H. Graeff)
ABSTRACT Orthotopic liver transplantation (OLT) is frequently associated with systemic fibrinogenolysis and diffuse bleeding. At present antifibrinolytic treatment has not been initiated routinely in OLT. Therefore the influence of high dose aprotinin in OLT (2 million kallikrein inactivator units (KIU) given after induction of anesthesia followed by a 500,000 KlUlh infusion throughout the operation) on intraoperative blood loss and fibrinolysis was studied in 25 patients compared to 25 patients without aprotinin. The incidence of fibrinolysis shown in thrombelastography was 72 O/O in the control group versus 16 % in the aprotinin group. Oozing after reperfusion of the graft caused by severe fibrinolysis defined as a clot lysis index below 15 % was only observed in the control group (42.8%). In contrast no significant difference was found between the groups in the course of fibrin and fibrinogen degradation product levels (FbDP, FgDP) afthough the mean concentrations of both parameters were evidently lower in the aprotinin treated patients. Levels of tissue-type plasminogen activator (tPA) activity were initially high in both groups and peaked during and after the anhepatic period. After aprotinin there was a trend of lower t-PA levels which reached significance at the time of reperfusion (p ~0.02). In both groups the course of thrombin antithrombin complex was in line with the variations of FbDP and FgDP. No correlation between thrombin formation and t-PA activity was found. Mean homologous blood requirement was reduced by 50 O/O (5.6 f4.G vs. 11.2 +8.6 units, p eO.005) The blood saving effect was more pronounced in the postanhepatic period (p 4 pts were considered as severe hemostatic impairment)(Tab. 1).
TABLE 1 Patient Data and Type of Operation
Age (years) Hematocrit (~01%) Coagulation score (points) Previous laparotomy (n) Cell Saver (n) Veno-venous bypass (n) Anhepatic time (min) Total operation time (min) Indications (n) Liver cirrhosis Acute hepatic failure Retransplantations Liver tumors Miscellaneous
Aprotinin group n = 25
Control group n = 25
41.7 f 13.4 28.2 f 3.1 5.8 ? 2.7 9 19 20 104.0 f 57.8 374.1 f 79.4
42.0 +12.9 27.8 + 4.4 5.2 + 2.9 7 21 20 83.0 + 23.4 375.9 + 80.1
12 2 3 3 5
13 3 3 4 2
Resutts of the fibrinolytic aa Preoperatively we found in the control group a state of enhanced fibrinolytic activity with reduced levels of plasminogen and a2-AP, moderatly elevated levels of t-PA and
290
APROTININ IN LIVER TRANSPLANTATION
Vol. 63, No. 3
markedly increased concentrations of fibrin- as well as fibrinogen degradation products (A in Fg.1, 2). During the surgical procedure plasminogen showed minimal changes and increased towards the end of surgery. Levels of a2-AP remained below baseline values throughout the operation with a sighificant transient decline at time of graft recirculation. During the course of PAI- we found a continous drop from 14.9 fll.7 AU/l after induction of anesthesia to 1.6 f5.1 AU/l after recirculation of the graft (p ~0.00001). At that time PAI- activity was undectable in a number of patients. At the end of transplantation the mean levels were found above normal (22.4 f15.7 AU/l) (Fig. 1).
90
80
40
1
!?!G_.l Changes in plasminogen, a2-antiplasmin and plasminogen activator inhibitor-l in the control group. Meansf SD,differencesfromA statistically significant: p
