1984 63: 525-531. Z Borok, J Weitz, J Owen, M Auerbach and HL Nossel ...... Morris. RH,. Vassali. P. BelIer. FK,. McCluskey. RI: Immuno- fluorescent studies.
From bloodjournal.hematologylibrary.org by guest on July 12, 2011. For personal use only.
1984 63: 525-531
Fibrinogen proteolysis and platelet alpha-granule release in preeclampsia/eclampsia Z Borok, J Weitz, J Owen, M Auerbach and HL Nossel
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From bloodjournal.hematologylibrary.org by guest on July 12, 2011. For personal use only.
Fibrinogen
Proteolysis
and
Platelet
a-Granule
Release
in
Preeclampsia/Eclampsia By Z. Borok, Serial
measurements
nopeptide
A,
flecting
of the
and
and
after
sia.
The
platelet
data
were
hematologic
clinical
manifestations.
sia.
there of
were
marked
increases
platelet these patients
A
no
in the
other
during,
preeclampsia
proteins.
were
coagulation as with
mild
THE
were and
correlated
with
in time
the those
material stained with fibninogen.2 Increased degradation
products
infu-
changes
this to of
in the
Abnormal perfusion lung pulmonary emboli, were with preeclampsia and 6/8
by thrombin proteolysis measured as thrombin-increasable
1 -42,
stud-
I.
fibnin II formation by thrombin Beta thromboglobulin (BTG)
factor
4
(PF4)
reflect
alpha
of fibnin (B1-13)
proteolysis of and platelet
granule
increase
in
release
from
platelets.
platelet
fibrin
normotensive
in the first
of 30 mm
Informed
consent
METHODS
were
through
delivery
pressure
of at least
140/90
Blood,
Vol. 63,
No. 3 (March),
1984:
mm
Hg
in patients
pp. 525-53
1
who
had been
and
a week.
Daily
and
protein
creatinine collections.
of
that
a
contributed
patients
to
with
severe
fibrinopeptide possibly
of pregnancy,
B
reflecting
or an increase
of I 5 mm from
Hg over
in systolic
baseline
values.
all patients.
Records hyperreflexia,
Blood
Collection
Samples
20 mM
BTG
Four
lant
ml
were
determined
3.8%
determination,
1,400
tube
were
tested
for
twice
via
U/mI,
a tube
the
pH
urine of
/0.
and
University.
to
PF4
and
needle
into
anticoagu-
1/100
volume
counts
and
studies protein
into
and
FDP
for
blood
assays
of collection,
Columbia York,
Trasylol theophyl-
FPA,
was collected
platelet
30 mm
the
University,
were
plasma
College
NY. HL-15486,
HL-21006,
and
of Health.
accepted Dr.
of and
into
platelet
blood and
Grants
/983;
tube
For
collected
Institutes
requests
and
a plastic
via the same
for coagulation
within
by Research
7.4.
a 2 1-gauge
I ml of the same
were
of clotted
National
Columbia
on 24-hr
for TIFPB
into
10 mM,
ofMedicine,
February reprint
and
using
blood consisting
containing
New
vein
solution, saline,
Surgeons,
inpart
3
protein,
noted.
adenosine
citrate
ice, and
and
for
collected
the presence
were
a syringe
leukocyte,
the Department
and
milliliters
for fibrinopeptide
on melting
weekly
pressure,
an antecubital
samples
trisodium
and
from
were
in mentation
one-half
hematocrit,
Tubes
ofPhysicians
levels
of blood
from
Additional
1/10
Samples
Processing
and
vacutainer
volume
kept
to the study
hospital.
FDP
9 ml was then collected
for
From
samples
in HEPES-buffered
I 5% EDTA
placed
urine
and platelet
of admission
from
and
anticoagulant
heparin
solution.
chemistry.
tests,
was collected
measurement,
a siliconized
discharge
collected
0.5
U/mI,
until
were
measurement
1,000
the time
or changes
needle.
containing
from
and
were
butterfly
of fibrinopeptides
daily
coagulation
edema,
Medicine,
blood
suggesting
desarginyl
for measurement
times
(c)
half
collected
counts,
geons,
these
degree
vessels.
was obtained
blood
Address
The patients studied were admitted to hospital with a diagnosis of preeclampsia or eclampsia. The criterion for entry to the study was a
in
the
have
in two
in and
seen
level.
insufficiency.
Hg or diastolic
Blood samples proteins
Submitted
Patients
coagulation
to must
as
Protocol
Supported
AND
indicating
were
(4)
in renal
hours
saline.
levels
high renal
pressure
Study
and
fibrinopeptides
thrombocytopenia
A
on with
several
intravascular
thrombin
changes;
II formation
in for
disproportionate than
action
in patients
severe
fibrinopeptide
preceded
HL-0746/
MATERIALS
protein
other
(2)
than
to
preeclamp-
plasmin
increase
(3)
were
severe
of hypertonic
stimulus
the
mechanism
line
of fibninogen; Bf3 fibninopep-
tide B (TIFPB), reflects plasmin degradation I to form fragment X; and desarginyl FPB reflects fibrin
and
Bl-13
on fibninopeptide and platelet alpha granule levels as indices of fibninogen proteolysis and release. Fibninopeptide A (FPA) reflects fibnin
I formation
the rather
infusion
platelet
patients
of
and
patients with eclampsia.9 Because of these findings, we undertook serial ies in a group of patients with preeclampsia/eclampsia, focusing protein platelet
persistent
the
factor VIII level, thrombocytopenia, decreased platelet survival, and increased fl-thromboglobulin (BTG) 1evels have been reported.38 scans, thought to reflect observed in 10/19 patients
a more
with when
of thrombin;
7 days,
the
levels
antiserum and levels
(FDP),
after
in
in the glomeruli,
fluorescent-labeled fibninolytic activity
occurred
that
eclampsia
3 to
occurring
Electron microscopy patients with preeclampsia
material
I
from
preeclampsia/eclampsia.
saline
(1 ) patients presented
exceeded
in
hypertonic
that:
usually
changes
of preeclampsia/ there is much evidence for in the disease. Widespread a prominent histologic find-
ing in fatal cases ofeclampsia.’ renal biopsy material from
noted
increased 5
ETIOLOGY
eclampsia is unclear, intravascular coagulation fibnin deposition has been
fibninoid
In
fibrinopeptides
H. L. Nossel
preeclampsia/eclampsia;
at the there
When
intraamniotic
the
preeclamp-
changes.
which
compared
lasted
fibrinopeptides
of
manifestations.
LTHOUGH
fibninogen
before.
preeclampsia/eclampsia.
undergoing
has shown
fibrinogen
hematologic levels
it was
throm-
as well with
and
sia/eclampsia
B, beta
routine
status.
increases
granule
patients
renal
(re-
preeclampsia/eclamp-
with
in plasma
clinical
made
with
In 1 1 patients
severe
alpha the
and
but
with
4 were
correlated
small
delivery,
patients
with
factor
in patients
studies,
time
fibrinopeptide
B
M. Auerbach, sion.
of fibri-
fibrinopeptide
desarginyl
delivery
J. Owen,
concentration
thrombin-increasable
B/9 1 -42).
boglobulin,
plasma
J. Weitz,
September
Jeffrey
College
630 West 168 Street. New York, /984 by Grune & Stratton, Inc.
Weitz, of
NY
/4.
1983.
Departnent
Physicians
and
of Sur-
10032.
0006-497//84/6303-0005$0/.00/0
525
From bloodjournal.hematologylibrary.org by guest on July 12, 2011. For personal use only.
526
BOROK
was separated assay and -
by centrifugation
of FPA, 0.5
PF4,
ml
of
and
for
BIG
platelet-poor
plasma
80#{176}C, for assay of the platelet
stored
at
to FPA tated
with
assay
were
ethanol
with
previously
described.”
bentonite
and
stored
at
plasma
Bl-l3
Samples neutralizing
for Bl-13
with
and
was
with bentonite
and
after
for
assay
prior
was
precipi-
for
TIFPB
heparin,
were
carboxypeptidase
as
adsorbed
B,
as
with
previously
described.2
Radioimmunoassays FPA,’3
Bl-l3,’2
previously between PF4
TIFPB,”
described.
The
6 and 48 ng/ml,
is between
ng/ml.’3
1.7
In our
pmole/ml,’
BTG, normal with
and
TIFPB
PF4’4’3
21
ng/ml, the
value
assayed
a median
in normals
pmole/ml,”
as
in our laboratory
of I 8 ng/ml,’4
with
level
is
