1
I
I
Anesthesiology
66:i66-77:5. 1987
Reprinted
from:
ANESTHESIOLOGY.
Vol.
66.
No.
6.June 1987
Epsilon-aminocaproic
Acid
for
Treatment
of
Fibrinolysis
during
Liver
Transplantation
Yoogoo Kang, M.D.,· Jessica
H.
Lewis, M.D., t Ashok Navalgund, M.D., • Michael
W.
Russell, M.D.,·
Franklin
A.
Bontempo,
M.D.,l
Lawrence
S.
Niren, M.D.,· Thomas
E.
StaS
M.D., Ph.D.§
In
97
adult
patients
receiving liver
transplants,
the
coagulation
system was
monitored
by
thrombelastography
and
by
coagulation
profile including
PT;
aPTT;
platelet count; level
of
factors
I,
II,
V,
VII,
VIII,
IX,
X,
XI,
and
XII;
fibrin
degradation
products;
ethanol
gel test; protamine gel test;
and
euglobulin lysis time. Preoperatively,
fibrinolysis defined
as
a whole blood clot lysis
index
of
less
than
80% was
present
in
29
patients
(29.9%), and a
euglobulin
lysis
time
of
less
than
1 h was
present
in
13
patients.
Fibrinolysis
increased
progressively
during
surgery
in
80 patients (82.5%)
and
was
most
severe
on
reperfusion
of
the
graft
liver in 33
patients
(34%).
When
whole blood clot lysis
(F
< 180 min) was observed
during
reperfusion
of
the
graft
liver,
blex>d
coagulability was tested
by
thrombelastog-
raphy
using both a blood sample treated in vitro
"ith
t-aminocaproic
acid (0.09%)
and
an
untreated
sample. Blood
treated
with
...
amino-
caproic
acid showed
improved
coagulation
without
fibrinolytic ac-
tivity
in
all
74
tests.
When
whole blood clot lysis
time
was less
than
120 min, generalized
oozing
occurred,
and
the
effectiveness
of
t-
aminocaproic acid was
demonstrated
in
vilro
during
the
pre-anhe-
patic
and
post·anhepatic
stages, t-aminocaproic
acid
(1
g,
single
in-
travenous
dose) was
administered.
In
all 20
patients
treated
with
Eo
aminocaproic
acid, fibrinolytic activity
disappeared;
whole
blood
clot lysis was not
seen
on
thrombelastography
during
a 5-h
obser-
vation period,
and
whole
blood clot lysis
index
improved
from
28.5
± 29.5%
to
94.8 ± 7.4%
(mean
± SD, P < 0.001).
None
of
the
treated
patients
had
hemorrhagic
or
thrombotic complications.
In
patients
undergoing
liver
transplantation,
the judicious
use
of
a
small
dose
of
t-aminocaproic
acid,
when
its
efficacy was
confirmed
in
vitro, ef-
fectively treated
the
severe
fibrinolysis without
clinical
thrombotic
complications. (Key
words:
Blood: coagulation; fibrinolysis. Liver:
transplantation.
Measurement
techniques:
thrombelastography.
Pharmacology:
...
aminocaproic
acid.)
ORTHOTOPIC
LIVER
TRANSPLANTATION
is
frequently
associated
with surgical bleeding that requires massive
blood transfusion.
1
The
surgical bleeding
is
compounded
by preexisting coagulopathy, dilutional coagulopathy,
fi-
brinolysis, and, possibly, disseminated intravascular co-
agulation.
2
In a
recent
series
of
patients undergoing liver
transplantation,
the
degree
of
coagulopathy
and
volume
of
transfusion decreased with the introduction
of
replace-
ment therapy guided by the frequent thrombelastographic
• Assistant Professor, Department
of
Anesthesiology.
t Professor, Department
of
Medicine.
:j:
Assistant Professor, Department
of
Medicine.
§ Professor,
Department
of
Surgery.
Received from the Departments
of
Anesthesiology, Medicine,
and
Surgery, University
of
Pittsburgh
School
of
Medicine, Pittsburgh,
Pennsylvania. Accepted
for
publication
January
18, 1986.
Dr.
Russell'.
current
address
is
Medical College
of
Virginia, Richmond, Virginia.
Address reprint requests
to
Dr.
Rang:
Department
of
Anesthesiology,
Presbyterian-University Hospital,
Desoto
"
O'Hara
Streets, Pittsburgh,
Pennsylvania 15215.
\.
766
......
monitoring
of
the coagulation system and the use
of
hep-
arin-coated veno-venous
bypass.~·4
However, active fibri-
nolysis, manifest
as
generalized oozing from a previously
dry
surgical field
and
unresponsive
to
replacement ther-
apy, has been a major difficulty in
the
intraoperative man-
agement
of
liver transplantation.
Since
the
early experience in hepatic transplantation.
activation
of
the fibrinolytic system has been recognized,5.6
and,
although antifibrinolytic
treatment
appears benefi-
cial, it has been used only sporadically. Von Kaulla
et
al..
on
the
basis
of
postoperative thrombotic complications in
patients with hepatic neoplasms, suggested that admin-
istration
of
E-aminocaproic acid (EACA) might be harmful
in transient fibrinolysis,6 whereas Flute
et
al.
suggested a
possible beneficial role
of
EACA in patients receiving liver
transplants.?
Thus
far, anti fibrinolytic therapy has been
empirical; its indications have
been
ill defined, monitoring
of
fibrinolysis has
been
inadequate, and, usually, a large
dose
of
EACA has been used in cases
of
uncontrolled
bleeding. We designed the present study
to
investigate
the
significance
of
fibrinolysis.
to
evaluate
the
clinical ef-
fectiveness
of
EACA,
and
to
identify a clinically effective
dose
of
EACA in patients receiving liver transplants.
Methods
After
the
study protocol was approved by the Institu-
tional Review Board for Biomedical Research
at
the
Uni-
versity
of
Pittsburgh, adult patients undergoing liver
transplantation between
October
1983
and
January
1985
were
observed prospectively.
Two
8.5-French in-dwelling
catheters were inserted for volume infusion, one in the
antecubital vein,
and
another
in
the
external
or
intema1
jugular
vein. In addition, a flow-directed pulmonary ar-
tery
catheter with on-line oximetry
was
inserted via the
right
internal
jugular
vein,
and
two indwelling intraar-
terial catheters were placed in
the
radial arteries,
one
for
pressure monitoring,
and
one for blood sampling and
back-up pressure monitoring. A heparin-coated
vena-ve-
nous
bypass system (Biomedicus Inc., Minnetonka, MN)
was used in all patients during
the
anhepatic stage. A
rapid-infusion
systemS
was
used to replace lost blood vol-
ume
with a fixed fluid composition
of
packed red blood
cells (RBC), fresh frozen plasma (FFP),
and
electrolyte
solution
(Plasma-Iyte A-, Travenol Laboratories
Inc~,
Deerfield,
IL
60015) in a ratio
of
300:200:250 mi. FFP
was
added
to prevent dilutional coagulopathy.
The
blood
-----_.-----_
...
_------
767
KANG
ET
.J.,L
A"""t..-wologr
v 66, No 6,
Jun
1987
mixture yielded levels of: fibrinogen, 130 mg%; factor
II,
0.59
U/ml;
factor
V,
0.21
Vlml;
and factor VIII,
0.57 U/m!. Electrolyte solution
was
added
to
decrease
hematocrit to
27
±
2%,
to reduce the
loss
of
RBC,
and
to
improve circulatory rheology. Transfusion
of
additional
blood components was guided by variables measured by
thrombelastography (TEG): 2 units
of
fresh frozen plasma
were given when reaction time was longer
than
15 min,
10 units
of
platelets when maximum amplitude was less
than
40 mm, and 6 units
of
cryoprecipitate when clot
formation rate
was
persistently less than
40°.
TEG
is
shown schematically in figure
1.
The
device
consists
of
a highly polished stainless steel cup
that
contains
whole blood
(0.36 ml)
and
a pin freely suspended by a
torsion wire.
The
temperature
of
the cup
is
kept
at
37°
C.
It
oscillates on its vertical axis
of
4.45 ° every 9
s.
Ini-
tially. blood injected into
the
cup
remains fluid,
and
the
oscillation
of
the cup
is
not transmitted
to
the
pin. As
fibrin strands form between the surfaces
of
the
cup
and
the pin, the shear elasticity
of
fibrin strands increases,
and
the motion
of
the
cup
is
coupled to
the
pin.
The
motion
of
the pin,
in
tum,
is
transmitted to
the
torsion wire
and
recorded on thermal paper.
Therefore,
TEG
monitors
the entire process
of
coagulation, including the initial fluid
state without fibrin strands,
the
gradual increase in
strength
of
fibrin strands (coagulation), and
the
resolution
of
fibrin strands (fibrinolysis).
The
variables measured by
TEG
are: reaction time (r [min]), coagulation time (r + k
[minD, clot formation rate (a
[0]),
maximum amplitude
(MA [mm
]),
amplitude
60
min
after
maximum amplitude
(~[mm]),
whole blood clot lysis index (WBCLI,
Awl
MA·
100
[%
D,
and whole blood clot lysis time
(F
[min])
(fig.
2).
The
surgical procedure
is
divided into
three
stages,
according to distinctive anatomic
and
physiologic altera-
tions at each stage.
The
preanhepatic stage (stage 1), be-
gins at induction
of
anesthesia
and
.ends
a,t
!!.epatectomy-
The
anhepatic stage (stage 2) is
the
period
between
hep-
atectomy and reperfusion
of
the graft liver
by
portal ve-
nous blood.
The
postanhepatic stage (stage 3) lasts from
reperfusion
of
the graft liver
to
the
end
of
surgery.
EVALUATION
OF
FIBRINOLYSIS
Blood samples (15 ml each) were obtained from
an
un-
heparinized indwelling arterial
catheter
for coagulation
monitoring at the following times: before induction
of
anesthesia; 30 min into surgery;
thereafter
every 2 h
or
after
infusion
of
every 6 I
of
fluid volume; 5 min
before
removing the liver; 5 min into
the
an hepatic stage;
30
min into the anhepatic stage; 5 min before reperfusion
of
the graft liver; 5 min
after
reperfusion
of
the
graft
liver;
SO
min after reperfusion
of
the
graft
liver;
and
thereafter every 2 h
or
after every 6 I
of
fluid infusion.
Pin
Torsion
wire
t.
)
If. •
\'-Fibrin
strand
14.45..\
Recording
FIG.
1.
Schematic diagram
of
thrombelastography.
The
blood samples were tested by
TEG
and
coagulation
profile. Whole blood
(0.36
ml) was used for
TEG
tests,9
and
recordings
began
4
min
after
blood sampling. Mea-
sured coagulation profile variables included platelet count;
prothrombin
time (PT); activated partial thromboplastin
time (aPTT);
thrombin
time
(TT);
reptilase time (RT);
level
of
factors I,
II,
V,
VII,
VIII, IX, X, XI,
and
XII;
fibrin degradation
products
(FDP); ethanol gel test; prot-
amine
gel test;
and
euglobulin lysis time (EL
T).lO-12
Fi-
brinolysis was defined
to
be
present
when complete whole
blood clot lysis was
observed within 3 h
or
when whole
blood clot lysis index (WBCLI)
was
less
than
80%.
EVALUATION
OF
EACA
IN
VrrRO
-
When blood clot lysis
time
(F)
_was
less than 180 min
or
5 min
after
reperfusion
of
the
graft
liver, two blood
4 min
F
---~)j
FIG.
2.
Variables measured by thrombelastography
and
their normal
values: r = reaction time (min); r +
...
- coagulation time (min); a
= clot formation rate (0); MA - maximum amplitude (mm);
"-
-
amplitude 60 min
after maximum amplitude (mm); F = whole blood
clot
lysis
time (min): and
WBCU
= whole blood clot
lysis
index
("-I
MA·lOO,
%).
;
I
i
'1
I
A...w...iology
v 66.
No
6. Jun
1987
ANTlFIBRINOLYTIC
THERAPY
IN
LIVER
TRANSPLANTATION
768
TABLE
I.
Thrombelastographic
Variables
and
Coagulation
Profile
in
the
Preo~rative
Period
and
in
the
Most
~ct.ive
Fi~rinolytic
Stage
in
SO
Patients
Who
Showed
FlbnnolyslS
Normal
V~riable
V.I_
Preop<ntM Period
Fibrinolytic
Stage
Reaction
time
(min)
6-S
9.S8±
7.66
10.71±12.1
Coagulation
time
16.7
±
12.S
14.1
±
7.0
(min)
10-12
Maximum
amplitude
(mm)
50-70
44.8
±
14.S
S2.6
±
15.6*
Clot
formation
rate
(0)
>50
42.1
±
16.4
S6.6
±
18.S*
Whole
blood
clot
lysis
index
(%)
>80
SO.9
±
17.4
2S.9
±27.7*
Prothrombin
time
(5)
II-IS
14.7
±
S.7
15.5
±
S.4*
Activated
paniaJ
thromboplastin
time
(5)
26-S4
46.5
±
21.8
60.2
±S2.5*
Thrombin
time
(5)
IS-IS
26.8
±
11.6
29.7
±
1:5.1
Platelet
count
(IOOO/mm')
150-450
122.4
±
128.8
92.8
±
58.7*
Fibrinogen
(m~)
150-450
198.0
±
10S.S
129.S
±66.0*
Factor
II
(U/m!)
0.5-1.5
0.5S±
0.25
0.50±
0.17*
Factor
V
(U/mI)
0.5-1.5
0.47±
0.29
O.SO±
0.15*
Factor
VII
(U/ml)
0.5-1.5
0.47±
0.S2
0.S8± 0.21·
Factor
VIII
(U/ml)
0.5-1.5
1.79±
0.87
1.22±
0.70·
Values
are
means
±
SD.
• P <
0.05
compared
with
preoperative
values.
samples were tested
by
TEG; one sample (0.33
ml)
was
treated with 0.03
ml
of
EACA
(1
% solution). and the
other
(0.36
ml)
was
untreated blood.
The
TEG
variables
measured in EACA-treated blood and in
untreated
blood
were compared.
Wilcoxon test for paired data, and analysis
of
variance
of
repeated measures. and specific differences were assessed
with the Student-Newman-Keuls test.
P < 0.05
was
con-
sidered statistically significant.
Results
EVALUATION
OF
FIBRINOLYTIC
ACTIVITY
Seventy-nine patients received 97 liver transplants
during the study period;
18
operations were retransplan-
tations.
On
82 occasions. a complete preoperative coag-
ulation profile
was
available: average
PT
was
IS.0 ± 3.9
s;
aPTT.
46.4 ± 23.4
s;
TT.
26.8 ± 11.4
s;
RT. 24.6
± 7.6
s;
platelet count. 133.800 ±
142.700/mm'.
All
co-
agulation factors except fibrinogen (199.S
± 115.4
mg%)
and
factor VIIl (1.78 ± 0.81
V/ml)
were 30-60%
of
normal. Preoperative TEG values were available
in
a1l97
patients; they showed prolonged reaction time (r.
10.2
± 7.7 min) and coagulation time
(r
+ k. 17.8 ± 13.S min).
decreased maximum amplitude (MA. 44.6
± 14.S
mm).
and
decreased clot formation rate (a. 40.9 ± 17.0°). Pre-
operative
fibrinolysis
was
demonstrated by
TEG
as
a
whole
blood clot
lysis
index (WBCLI)
of
less than 80%
in
29
patients
(30.S%) and complete whole blood clot
lysis
within 3 h
in
4 patients. In
13
of
84 patients (IS.S%).
ELT
was
1 h
or
less
preoperatively.
Intraoperatively.
17
patients (17.5%) showed no sign
of
fibrinolysis (group
1).
while
80 patients (82.5%) showed
signs
of
fibrinolysis (WBCLI < 80%
or
F < 180 min) in
at
least one blood sample during
the
surgical procedure
(group
2).
The pre- and intraoperative coagulation profiles
of
patients
in
group 1 were not different from those in
CLINICAL
ApPLICATION
OF
EACA group 2 (P = 0.20). In group 2. fibrinolysis
was
most
.
....
severe during the preanhepatic stage in
21
patients
When severe
fibrinolysis
(F <
120
min)
and
generalized (26.2%). during the anhepatic stage in 19 patients (23.8%).
_ oozing occurred during s.urgery.
a.n.dfibJin.oly'si;s
~~
pre.",.,~.)~n~d~ring
the postanhepatic stage in 40 patients (50%).
....
vented
in
vitro
in EACA-treated blood.
as
evidenced by"' Fibrinolysis
was
most severe immediately afterreperfusion
an increase
in
whole blood clot
lysis
time (F). a single
1-
of
the graft liver
in
33 patients.
The
duration
of
fibri-
g dose
of
EACA
was
administered intravenously to
the
nolysis (WBCLI < 80%)
was
measured from
its
appear-
patient. However. when active fibrinolysis occurred near ance to its disappearance on the
TEG
recording. Mean
the anhepatic stage (from
30 min before removal
of
the duration
was
216 ± 136 min; duration
was
less
than 4 h
native liver to the completion
of
the hepatic arterial ana5- in 44 patients and
4-8
h
in
36 patients. No patient dem-
tomosis after reperfusion
of
the graft liver) EACA
was
onstrated fibrinolysis at the end
of
surgery. In table 1,
not given, to avoid possible clot formation
jn
. the vena- the coagulation profile and TEG values in the most active
venous bypass circuit. TEG and coagulation profile vari- fibrinolytic stage (defined by the minimum WBCLI) for
abIes were observed to
assess
the clinical effectiveness
of
group 2 patients are compared with preoperative values.
the anti fibrinolytic therapy.
To
evaluate
the
possible mi-
The
most significant thrombelastographic changes were
crocirculatory thrombotic effects ofEACA, postoperative a decrease
in
MA
from 44.8 ± 14.3
to
32.6 ± 15.6 mm.
renal function
was
assessed
by measuring blood urea ni- in clot formation rate
(a)
from 42.1 ± 16.4 to 36.6
trogen and serum creatinine levels
for
7 postoperative ±
18.S·,
and, in WBCLI, from 80.9 ± 17.4 to 23.9
days.
± 27.7%. Platelet count and all coagulation factor levels
All
measured variables are presented as mean ± SO. decreased. The frequency distribution
of
whole blood
dot
Data were analyzed
by
linear regression, nonparametric
lysis
time, ELT. FOP, and fibrin monomers
is
shown in
\.
'
..
_L
_______
..
_.
___ _
769
KANG
ET
AL.
Ann<
~ooiog)'
\.
66.
No
6.
Jun
1987
T.~BLE
2.
Intraoperati\'e
Changes
in
Whole Blood Clot
Lysis
:ri,:"e.
Euglobulin Lysis
Time.
Fibrin Degradation Products.
and
F.bnn
Monomers
in 68 Patients
Who
Showed Fibrinolysis
Number
or
Patienu
Preoperative
Fibrinolytic
\'ariabk
Period
SlOge
Whole blood clot lysis time
0-60
min
I
~6
61-120
min
0
25
121-ISO
min
3
S
>
ISO
min
64
4
Euglobulin lysis time
0-60
min
IS
49
61-120
min
7
4
>120
min
4S
15
Fibrin
degradation
products
4S
o
JLg/ml
55
10-40
!,glml
5
7
>40
!'g/ml
S
IS
Fibrin
monomers
0
56
24
+
11
3~
++
1
10
+++
0
1
Whole blood clot
lysis
time
and
euglobulin
lysis
time decreased.
and
level
of
fibrin monomers increased.
during
the fibrinolytic stage.
table 2. Whole blood clot lysis time
(F)
was
less than 120
min in
one
patient preoperatively and in
61
patients
at
the most severe fibrinolytic stage
(P
< 0.05).
The
changes
in
EL T were similar.
The
number
of
patients who showed
positive soluble fibrin monomers increased during
the
most severe fibrinolytic stage.
but
the increase in FDP
was
not
significant.
In
group
2 patients. fibrinolysis mea-
sured as
EL
T did not correlate with whole blood clot lysis
time (F)
or
whole blood clot
lysis
index (fig. 3).
Ev
ALVA
TION
OF
EACA
IN
VITRO
When fibrinolysis (F < 180 min)
was
observed
and,
5
min
after
reperfusion
of
the
'graft
li:;e~;;th~:TE(f~aiuei
'~.'
in
untreated
blood were compared with those in EACA-
treated blood (n
= 74) (table 3.
fig.
4).
In
treated blood,
all
TEG
values improved: WBCLI increased from'
48.9
± 42.2%
to
93.6
± 16.9%.
and
whole blood clot
lysis
did
not occur
during
the 5-h observation period in all 74 cases.
CLINICAL
ApPLICATION
OF
EACA
EACA
(1
g)
was
administered intravenously to 20 pa-
tients who
had
oozing from a previously dry surgical field
and
severe fibrinolysis
(F
< 120 min) that
was
reversed
by EACA
in
vitro.
EACA
was
given during the pre-an-
hepatic stage in
five
patients
and
after reperfusion
of
the
graft liver in 15 patients. Preoperative coagulation profile
and
TEG
values in patients given EACA were similar
to
those in patients
not
given EACA.
TEG
and
coagulation
c
'E
t-"
180r-------~---.----------------~
EL
T : 18.1 +
0.54
F
(r2:
0.29,
NS)
•
jj
120
--
CII
.§
-
II)
.;;;
>-
.5
60
"S
.Q
0
'61
~
w
o
60
120
180
Whole
blood
clot
lysis
time
(F, min)
FIG.
3. Relation between whole blood clot
lysis
time (F)
and
eu-
globulin
lysis time (EL
T)
in patients who demonstrated fibrinolysis.
The
correlation
was
poor
(r
= 0.29).
profile variables measured before
and
10 min after the
administration
of
EACA are shown in tables 4
and
5 and
figure 4.
The
improvement in coagulability
is
shown by
increases in
MA
and
WBCLl and whole blood clot
lysis
time
(F) longer than 5 h in all patients. But EACA did
not
improve the coagulation profile significantly except
for
a
moderate
increase in
EL
T.
In all patients given
EACA, oozing from
the
surgical field stopped immedi-
ately.
and
whole blood clot
lysis
did not recur.
The
clinical course
of
all patients
was
observed for
thrombotic
complications.
Four
patients suffered throm-
TABLE 5. Thrombelastographic Variables in Untreated Blood
and
in
Blood
Treated
with f-aminocaproic Acid (n = 74 Tests)
Normal
Untrealed
IIlood
Trwed
Variable
V.lua
IIlood with EACA
Reaction
time
(min)
6-S
9.6±
5.4
S.I
±
4.2·
Coagulation
time
(min)
10-12
24.S±
IS.O
19.2±
S.2·
Maximum
amplitude
(mm)
50-70
33.0 ± 14.9 40.3 ±
15.4·
Clot
fonnation
rate
(0)
>50
30.7 ± 16.7
S6.4±17.1·
Whole
blood
clot
lysis
index
(%)
>SO
48.9±42.2
93.6±
16.9-
Whole
blood
clot
lysis
time
(min)
>ISO
62.6±
38.S
>ISOt
Values
are
mean
± SD.
• P <
0.05
compared
with corresponding values in untreated blood.
t
Whole
blood
clot lysis time
was
greater
than
180 min
in
all tests.
J
J
As>nth<siology
....
NTIFlBRINOLYTIC
THERAPY
IN LIVER
TRA~SPLASTATION
770
\'
66.
No
6.
Jun
1987
120
mln
in
surgery
-
The
anhepat
lC
stace
5
mln
after
reperf"
•.
on
JUntreated
blood
} Blood
treated
wi
th
[ACA
(0.091)
-[ACA
(1g).
IV--+
30
min
after
reperfuslon
End
of
surgery
o
30
60
90
120
180
min
FIG.
4.
Thrombelastographic
patterns
in
a
patient
undergoing
liver
transplantation.
t-aminocaproic acid (EACA. I g) was
administered
intravenously when severe fibrinolysis was observed
on
thrombelas-
tography. generalized oozing
occurred
in
a previously
dry
surgical
field
and
EACA treated fibrinolysis
in
vitro.
botic
or
hemorrhagic complications intra-
or
postopera-
tively: two pulmonary emboli, one hepatic arterial throm-
bosis
of
the grafted liver, and
one
subarachnoidal hem-
orrhage. None
of
these patients had received EACA.
Postoperative renal function measured by blood urea ni-
trogen and serum creatiniJ)(: levels
was
similar
in
the two
groups for 7
days.
TABLE
4.
Thrombelastographic Variables
and
Coagulation Profile in
Patients who Received t-aIIIinocaproic Acid (EACA. I g)
Variable
Before
EACA
10
Min
Alin
EACA
Reaction time (min)
11.1
±
II.!
S.S
±
S.S
Coagubtion
time
(min)'
21.1
±22.9
14.2
± 6
••
Maximum amplitude (mm)
'5.9
± 12.8 49.S
± 5.7*
Clot formation rate (0)
'7.6
± 19
.•
44.S
±n.6
Whole blood clot lysis
index
(%)
28.5
±29.5
94.S ± 7.4*
Whole blood clot
lysis
time
(min)
75.7
±S4.6
>IS0t
Prothrombin
time
(5)
16.0
±
1.9
16.S
±
1.7
Activated partial
thromboplastin time (.)
62.5
±2S.1
57.6
±
15,0
Thrombin
time
(s)
50.4
± 10.9
gO.1
± 10.9
Platelet
count
(IOOO/mm,) 1S2.6
±80.5
llS.1
±S6.5
Fibrinogen (mg'.l)
12S.2
±48.1
124.2
±3S.9
Factor II
(U/mJ)
0.46±
0.11
0.45±
0.11
Factor V
(U/mJ)
0.22±
O.OS
0.20±
0.06
Factor VII (u/m!)
O.gS
± 0.10
0.g4±
0.09
Factor
VllI
(u/mJ)
0.9S±
0.67
0.91
± 0.62
Values
are
mean ± SD.
* P < 0.05 compared with themrresponding values
before
EACA.
t Whole blood dot
lysis
time
was
greater
than
ISO
min
in
aD
oc-
casions.
TABLE
5.
Frequency
Distribution
of
Whole Blood Clot Lysis
Time.
Euglobulin Lysis
Time.
Fibrin Degradation Products.
and
Fibrin
Monomers
in
20
Patients Who Received
...
aminocaproic
Acid (EACA. I g)
Number
of
Patienu
Bd'o",
10
Min Aller
Variable
MCA
MCA
Whole
blood
clot lysis
time
0-60
min 9
0
61-120
min
11
0
121-1S0
min
0
0
>180
min
0
20
Euglobulin lysis
time
0-60
min
14
10
61-120
min
4 S
>120
min
2 2
Fibrin
degradation
products
o
Jlg/ml
10 8
10-40
Jlg/ml
7
8
>40
Jlg/ml
~
4
Fibrin
monomers
0
5
5
+
10
S
++
5 6
+++
0
1
Whole
blood
clot
lysis
time
and
euglobulin
lysis
time increased
10
min
after
EACA
administration.
Discussion
Fibrinolysis
is
well recognized in patients with acute
and chronic liver disease. Active fibrinolysis, manifest
as
weak blood
dots
or
generalized oozing that necessitates
continuous blood transfusion,
is
the most striking feature
of
the coagulation system during liver transplantation.
Cirrhotic patients
are
prone to fibrinolysis even after rel-
atively benign stimuli, IS and show an exaggerated fibri-
nolytic response to vasoactive substances. Delayed hepatic
clearance
of
circulating plasminogen activators, defective
synthesis
or
decreased levels
of
naturally occurring inhib-
itors, and activation
of
p~tein
C have been postulated
as
responsible for
the
fibrinolysis in patients with liver cir-
rhosis.14-
17
ll
However, it
is
controversial whether the
fi-
brinolytic activity in patients with liver disease
is
primary
or
secondary to disseminated intravascular coagulation,
mainly because
of
difficulties in differentiation
by
labo-
ratory tests.
II
In
our
experience. fibrinolysis occurring during liver
transplantation has appeared to be primary in origin.
Prolonged
PT
and
aPTT,
thrombocytopenia, hypofibri-
nogenemia, decrease in coagulation factors, positive fibrin
degradation products, positive soluble fibrin monomers,
and decrease in antithrombin III
are
the typical laboratory
,
Comp
PC, Esmon
CT:
Initiation
of
clot lysis
in
plasma by activated
protein
C (Abstract). Circulation 58:11-210, 1978
,.
