Normal Pregnancy in a Patient With a Prior

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Normal Pregnancy in a Patient With a Prior
From www.bloodjournal.org by guest on August 11, 2017. For personal use only.
Normal
Pregnancy
in a Patient
Inhibitor:
By
S. Coller,
Barry
A 22-yr-old
sis
after
and
the
titer
The
bleeding
pregnant
and
the
and
evidence
of
thymidine
of
of
into
her
own
THE
mo.
normal
of
incorporation
HILE
8
at
inhibitor.
the
patient’s
plasmas
of
first pregnancy
issuesfurther.
us
Coagulation
Blood
and
was
collected
22#{176}C
for 3.5 mm
AND
Platelet
activated
factor
30 mm
factor
for
partial
assays
plasma
for
employed
factor
Kasper
tion
Ct
saturated
IgG,
tor)
were
ammonium
N.J.).
ing
high-titer
studies
been
were
-
(for
or
one-stage
by
the
method
Immunoneutralizausing
antisera
factor
(ristocetin
clumping
Fab’
factor
VIII
on a single
70#{176}C
for between
Ten
syringe
for an additional
dpm
Blood,
containing
Vol. 58,
of blood
40
were
z1 of 1000
No. 3 (September),
drawn
1981
SEM
±
The
10
zI of
and
were
cells
processed
cells
so as to contain
i0
62 hr in a 5% CO2
were
then
collected
and
(Otto
Miller
described
counter
ratios.
(New
and the cells
harvester
as
the
The
was added
in a scintillation
standards
cells
methyl-3H-thymidine
6 Ci/mM)
automatic
of quintuplicate
Each
and
value
or sextuplicate
expressed
as
represents
cultures.
Brook,
Stony
Department
employfrom
bubbling
into
Abbott
The
the
signifi-
Lung and Blood
at the
18th
March
reprint
of New
of
Hematology,
Health
16626
and
Center.
16872
from
Institute.
of the
A ugust
to Barry
of
Medicine.
York
at Stony
& Stratton,
Division
19278.
1 7. 1 981; accepted
requests
by Grune
HL
Congress
Canada.
Department
University
11790.
(c) 1981
by Grants
Montreal,
the
of Medicine,
York at Stony
of Connecticut
Heart,
Address
a
and
the National
Submitted
had
Y.
University
Conn.
in part
Hematology,
VIII:CAg
N.
Farminglon,
Supported
Presented
two
that
Brook,
of Medicine,
Hematology.
(Panheprin,
plates
in
was added
U/mI).
using
antigen
on samples
without
heparin
external
( I0
times
contain-
The
to which
heparin
3
N.Y.)
the Division
of Hematology.
Department
Sciences Center, State University
of New
3 and 39 mo.
U/mI
using
Island,
streptomycin.
18 hr. The
Wisc.)
counted
of the
by centrifu-
washed
at 37#{176}C
for
Mass.;
on a multiple-sample
were
Grand
and
point,
processed
platelet
count
blood
then
medium
incubated
Boston,
Madison,
and
Gibco,
v/v)
incubated
From
Retention9”0
milliliters
that
mean
retained.
Health
to a modia water-
assay
prepared
antisera.8
occasion
At
heparinized
microculture
and
Nuclear,
mean
factor
coagulant
by an immunoradiometric
affinity-purified
environment.
into
ml)
EDTA.
platelet
cofac-
assay
Willebrand
VIII
aliquoted
(0.2
the
the
in 1 ml
Na3
to human
(Behring-Calbio-
VIll/von
then
cells/well
diameter
40%
chains
macroscopic
Factor
the
from
culture
( 10%
diameter
Studies
and 0.1 mg/mI
in the above
10%
the
tubing
mm
it as the percentage
1640,
penicillin
zI of
from
gradient
(RPMI
and
internal
of 0.5
by subtracting
separated
to be tested
Samples
of
were
twirled
6238,
10
milliliters
and expressing
in coun-
The blood was collected
Transformation
suspended
Co.,
Assay
6th
of
of polyvinyl
beads
containing
calculated
and
medium
England
and
as substrates.3
of rabbit
Factor
(VIII:C)
by a modified
units.
light
specific
tubes
was
5th
100 U/mI
State
Platelet
plastic
no.
N.J.).
completely
favorable
was gently
a column
g of glass
Carlstadt,
blood
plasma
syringe
Ni.,
2.6
had
pathogenesis
be considered
through
on a Ficoll-Hypaque
were
other
(Platelein-Plus,
activity
reported5
fractions
apparatus.
human
all
and
by electroimmunoassay
according
of Laurell7
in 1% agarose
utilizing
all performed
frozen at
studies)
(PTT)
performed
lambda
a timed
and
ing
then
The
Rutherford,
retention
heparinized
0.01
pregnancies.
containing
of the
culture
aggregtion
plasmas
Von Willebrand
was measured
radiolabeled
different
Platelet
should
Ill.).
second
postpartum
apparently
patients
at 5.7 mI/mm
into
count
at 1000 g at
plasma
measured
was
platelets.6
electrophoresis
(VIII:CAg)
amounts
the
her
literature
with
the
to future
Chicago,
Industries,
gation
containing
activator
as Bethesda
and
with
the
as previously
sulfate
was measured
of the method
cooled
titer
kappa,
assayed
(for
coagulant
were
performed
1gM,
as
VIII
hemophilic
formaldehyde-fixed
antigen
fication
North
pumped
(Potter
these
either
times
activity
inhibitor
Somerville,
was
Labs,
blood
(Becton-Dickinson,
employed
a rabbit-brain
source of
Diagnostics,
Morris
Plains,
N.J.)
known
al.4 and expressed
IgA,
chem,
using
VIII
assays
such
the
with
While
uncertain,
regard
0.1 18 inch)
Studies
platelet-poor
celite
Factor
IX coagulant
assay
for
with
of
inhibitors
delivery.
remains
Lymphocytes
tubes
thromboplastin
Diagnostics).
clotting
disorder
to
patient.
the
patients
whose
prior
immunologic
of
recurrences
8
a hemo-
of Vlll:CAg
discern
review
no
the
inhibitors
prognosis
METHODS
It was centrifuged
for platelet-rich
g at 4#{176}C
for
General
investigate
polypropylene
citrate.
assays).
Prothrombin
times (PT)
tissue factor
(Simplastin,
General
and
immuno-
of
to
A
and
Analysis
VIII:CAg
were
any
patient.
failed
child.
there
in
VIII
selling
has been well
state,’2
there
of such anti-
Aggregation
into
40% sodium
3500
to
that
first
and E. Roy Berger
results.
the
her
Lymphocyte
MATERIALS
volume
in
her
prognosis
of these
patients
pregnancies.
The
occurin a young
woman
after
her
stimulated
revealed
this
3H-
from
or
disappeared
lymphocytes
or
DEVELOPMENT
production
and the
regard
to subsequent
of such an inhibitor
of
husband.
H. Dosik,
Willebrand
antisera
VIII
Prognosis
equivocal
between
factor
preg-
a von
different
pregnancies
without
Studies
globulin
inhibitors
of factor
VIII
documented
to occur
in the postpartum
is scant
information
on the mechanism
body
with
rence
no
became
infant
2
Michael
yielded
differences
Factor
and
normals.
patient
using
(15
time
she
an uneventful
the
Postpartum
Joan V. Dobbs,
philic
inhibitor
which
later
female
plasma
VIII
Miller,
husband.
was
prednisone
Her
months
to have
a
a recurrence
presence
W
next
proceeded
delivery
with
thereafter.
Nine
and
of factor
treated
soon
detectable.
again
nancy
the
over
was
was
diathe-
infant
inhibitor
patient
stopped
decreased
inhibitor
female
an immunoglobulin
units).
Frederick
a hemorrhagic
a normal
a Prior
on Pathogenesis
Leon W. Hoyer,
developed
delivering
to have
Bethesda
Observations
Mae B. Hultin,
primigravada
6 days
found
With
With
International
Society
of
Division
of
1980.
May
/8.
S. Coller,
Health
Brook.
1981.
M.D..
Sciences
Stony
Brook.
Center,
N.
Y.
Inc.
0006-4971/81/5803-0029$0l.00/0
619
From www.bloodjournal.org by guest on August 11, 2017. For personal use only.
COLLER
620
cance of differences
test.
between samples
patient
confinement
rupture
of
slowly,
was
a 22-yr-old
8/27/77,
who 1d
membranes
requiring
delivery
ofa
same
by Student’s
period.
March
CASE
The
was determined
on
REPORT
primigravida,
the onset
the use of oxytocin,
normal
of labor
The
8/25.
with
initially
then
progressed
infant
(Apgar
date
with
10) on 8/26
12/10/79.
and
when
subsequently
The
fetus
was found
of labor
course
discharged
on 8/29.
and
was readmitted.
and
intravenous
a small
blood
clots
were
the
patient
On
9/7
considered
On 9/2
uneventful
the patient
She was treated
oxytocin
which
tively,
were
and
amount
from
became
vaginal
tissue
the
febrile
bleeding
was
unremarkable.
Factor
child’s
and the husband’s
plasmas
and
and
500
were
within
and
was
uterus.
which
.
during
and
Postopera-
treate&with
noted,
antibiotics.
persisted
despite
Three PTTs were performed
over the course of that day with values of 37.5, 31.0, and 42.5 sec
(normal < 35 sec). Other data obtained at that time were: PT I I .0
oxytocin
and
methergine
sec/control
I I .0 sec.
108/liter,
fibrin(ogen)
clot
normal,
lysis
on 9/8.
episiotomy
site;
this
was
was
stable
until
persisted
and
fresh
preparation
of
Coagulation
studies
mixing
frozen
cervix
300
curettage
was noted
to ooze.
was
from
tenacula
The
patient
sites
the
results
was given
estrogens
on 9/14
was
revealed
and
sec. The
shown
vaginal
PiT
every
bleeding
6 hr. On 9/ 1 3 a
added
P11’
a
normal
in Table
as having
to
of 44.0
plasma
remained
shown
in Fig.
several
months
range.
The
I
the
regimen.
sec and
tested
a PiT
immediately
patient’s
and
her
steroid
obtained.
to factor
VIII,
inhibitor
factor
therapy
VIII
was
titer
activity
tapered
declined
and
then
Factor
three weeks
neutralization
(70%),
anti-lgM
after
of
(40%),
at 3, 6,
performed
pregnancy
3H-thymidine
significantly
into
greater
plasma
than
plasma
(p
0.01 ).
normal
her
anti-kappa
the next
to the
stopped
normal
over
the
1 . Initial
>
0.05).
thymidine
presence
compared
(40%),
own
Also
plasma
(p
or von
102 dpm).
Laboratory
of note
This
can
<
0.05),
Willebrand
74/45
was
the
be taken
performed
(p
<
of a pool of 8
it did not differ
dramatic
to indicate
increase
an increase
sec
units
lgG and 1gM (no IgA)
kappa and lambda
cofactor)
light chains
90%
antigen)
184%
aggregation
ADP
2 waves
at 2.2
iM
(normal)
Epinephrine
2 waves
at 2.7
M
(normal)
Ristocetin
Normal
collagen
retention
being
hemophilic
sec
15 Bethesda
Immunoneutralization
factor
1gM
plasma
Result (Patient/Control)
time
(von Willebrands
anti-
lymphocytes
was
of her husband’s
Data
90%
antigen
and
in
incorporation
of the patient’s
cells in the
of normal
serum
( I I , 1 58 ± 353 dpm) when
to our experience
with 40 normals
(895
±
IX
Platelet
on plasma
in 1977 showed
by anti-IgG
p
VIII inhibitor
Platelet
the
was seen with antianti-IgA
in the assay
analysis).
Thus
the
The response
in the presence
plasmas
was intermediate;
Factor
Factor-VIII-related
performed
the
patient’s
in the presence
0.01),
<
Factor
(ristocetin
first
and
23 mo postpartum,
the
last
being
when the patient
was 4 mo into her second
(Table
2). At 3 mo the incorporation
of
8%
factor
on the
3 yr after
I 22%).
inhibitor
was polyclonal,
with both IgG and
detectable
as well as both light chain types.
Lymphocyte
transformation
studies
were
VIII
von Willebrands
and
the delivery
the inhibitor
lambda
(50%).
No neutralization
IgA
(the
presence
of excess
being
proven
by Ouchterlony
12.6/13.0
thromboplastin
1980,
(60
time
partial
( I 58
limits
assays
obtained
partial
Test
Activated
determinations
was
sec
sent to
where
Table
Prothrombin
VIII
patient
over
returned
breech
7 cm of
prednisone
at 44-47
The
and
footling
approximately
significantly
from the response
in the presence
of her
husband’s
plasma
(0.4 > p > 0.3), but when compared
to the response
in the presence
of her own plasma,
the
increase
was only of borderline
significance
(0.10
>
elevated
and plasma infusions discontinued.
On 9/20
minimal and the patient was discharged.
As
the
,
I were
an inhibitor
mg/day)
was started
the bleeding became
but
remained
over the next 4 days. A sample
of the patient’s
plasma
was
the State University
of New York at Stony
Brook on 9/18,
diagnosed
the
In addition,
at the
additional
x
40 tg/ml,
<
A second
continued
having
count
10 but
and I U of fresh plasma. The bleeding
plasma
of patient
of 29.1
mm.
to suturing.
began
conjugated
of a I : I mixture
after
the
well
with oxytocin
platelet
>
of bleeding
this
from
respond
9/ 1 1 , but then
and was treated
5.5
amount
suturing
bleeding
to
mg/dl,
products
time
A small
despite
some
said
300
degradation
bleeding
performed
there
treatment.
fibrinogen
after
in September
normal
Immunoneutralization
methergine,
ml of blood
in
RESULTS
was
bleeding
a curretage
vagina
was again
she
vaginal
2 U of blood,
underwent
of decidual
removed
had severe
with
then
and
to be a double
stopped
again
cesarian section was performed
with
of a normal female infant. The postpartum
delivery
low forceps over a median episiotomy.
The patient suffered a third
degree laceration of the perineum, but the repair and her immediate
postpartum
pregnant
and she went into labor
a primary
dilatation,
delivery,
became
was uneventful
course
first
by
patient
progression
the uneventful
progressed
well
on
cervical
of
spontaneous
labor
but
6 lb 14 oz female
estimated
The
1979. The pregnancy
ET AL.
initial
slope at 1 .8 and 1 .2 mg/mI
Normal
single
wave
>94%
(normal
>85%)
in
From www.bloodjournal.org by guest on August 11, 2017. For personal use only.
POSTPARTUM
FACTOR
VIII
INHIBITOR
621
DELIVERY
I
DELIVERY
DandC’s
500
I
400
‘I)
I
.
F
.
C
I
0
>
1o.
a,
300
a,
Ui
200
I5
z
Ui
PREDNISONE
100
\
(mg/day)
I
I-
z
AUG
SEP
OCT
:
DEC
NOV
JAN
77
1.
activity
of the
cells.
plasma
greater
response
in the
of the
with
response
presence
to the
Control
difference
incubated
husband’s
invalidated
in the presence
plasma.
Technical
the results
with
the
course
of patient
response
in the
and the normal
(p < 0.01)
than
patient’s
husband’s
strongest.
significant
own
plasma
with
and
278,
1307
again
being
of the patient’s
or her
problems
unfortunately
hemophilic
and von Wille-
Table
2.
±
223
tP
<
§Not
DEC
JAN
Studies
factor
3
Source
VIII inhibitor.
for comparison
raising
the
of patient
possibility
to each of the other
that
the patient’s
VIII
coagulant
antigen
studies
using
pregnancy
contained
the 2 antisera
and
first child’s
plasmas
112% and
129% VIIIC.
were found
I 23% VIII:CAg,
respectively
with the two antisera;
VIII:C
1 58%). Multip’e
dilutions
the plasmas
of her family
on Patients
Lymphocytes
(Mean
mo
108% VIII:CAg
The husband’s
to contain
130%
(averages
values
of the patient’s
members
gave
plasma
parallel
±
23
2,258
3,547
±
231
1,201
±
189
±
2,637
6,937
±
578t
2,925
±
47Sf
5.393
±
172t
Normalplasmapool
19.155
±
1,745
2.982
±
305f
Hemophilic
15.601
±
1,15O
3,889
±
170f
vonWillebrand
12,607
±
940
2,460
±
0.05
>
p
for a total of 80 hr in culture
the amount
compared
to patient plasma.
> 0.05
compared
to patient
significantly
different
compared
of 3H-thymidine
plasma.
to patient
plasma.
medium
containing
incorporated
10%
into DNA.
plasma
and.
lines
mo
±
incubated
with
and
and
SEM)
6 mo
13,751
were
2
at 3. 6. and 23 mo Postpartum
22.510
and determining
the
of the results
were
122% and
Husband
harvesting
fO. 10
NOV
OCT
Patient
‘Lymphocytes
before
SEP
antisera
revealed
l5%and
17%ofnormal
VII1:CAg
in
the patient
sample
obtained
at the time of diagnosis
(9/18/77);
that same sample
contained
8% VIII:C.
In
contrast,
a sample
obtained
9 mo after
the second
respectively;
Incorporation
postpartum
dpm
Plasma
AUG
80
plasma.
Factor
her second
pregnanagain
incorporated
the presence
of her
normal
pool plasma
but these
studies
dpm,
3H-Thymidine
JUL
plasma
had an inhibitor
of blast
transformation.
The
presence
of an inhibitor
of blast transformation
in the
plasma
of women
during
pregnancy
has previously
been
observed
by others.’2’3
The
response
of the
patient’s
cells to hemophilic
or von Willebrand
plasma
was not significantly
less than that to the patient’s
own
plasma,
were complicated
by the finding
that control
cells also
responded
less well in the presence
of the patient’s
plasma
than in the presence
of the husband’s,
pooled
normal,
hemophilic,
or von
Willebrand
plasmas
(717 ± 108 dpm
versus
1125 ± 99, 1868 ± 197,
±
JUN
MAY
p < 0.05
plasmas),
pool
the
studies
showed
that there
was no
in the response
of control
cells
brand
plasmas.
At 23 mo (during
cy),
the
patient’s
lymphocytes
more
3H-thymidine
into DNA
in
husband’s
plasma
(p < 0.01)
and
(p < 0.01 ) than
her own plasma,
2554
z
MAY
79
Clinical
At 6 mo,
presence
of the husband’s
were
both
significantly
the
I.
APR
78
Fig.
basal
“::.:
MAR
FEB
I
and 10 U/mI
heparin.
‘H-thymidine
was added
18 hr
From www.bloodjournal.org by guest on August 11, 2017. For personal use only.
COILER
622
in the immunoradiometric
sera
used
did
not
assay.
Thus,
the
recognize
significant
differences
between
the
and her family
members.
VIII:CAg
from
of plasma
two antiantigenic
the
patient
husband’s
tion may
The pathogenesis
of postpartum
factor
VIII
antibodies
remains
obscure.
One hypothesis
is that allotypes of factor
VIII exist and that the mother
becomes
sensitized
to the paternal
allotypic
determinants
inher-
was
ited by the fetus and that the antibodies
produced
then
cross-react
with the patient’s
own factor
VIII.
In fact,
circumstantial
evidence
has been advanced
to support
the idea that there are allotypes
of factor
VIII coagu-
fetuses,
mosome
mosome
lant
of the
cases,2
and
this
would
be
given the data with other proteins
Our studies
of blast
transformation
tional
support
to this hypothesis,
lymphocytes
DNA when
plasma
plasma.
quite
would
such
as hemoglobin.
lend some addisince
the patient’s
VIII
was
employed,
Table
3.
(3)
Results
a single
Willebrand
with great
Pregn ancies
away
occur
of
Report
194620
Author(s)
Chargraff
and West
Age
at
Prior
Obstetrical
Onset
History
criterion
30
1 Spont
ab
was
met
in our
responses
Hewlett
and Haden
39
1 Spont
Frick
24
own
Zbinden
and Leopold
Margolius
ab
would
VIII.
infusion
elicit
One
of
that
the
pregnant
state
immune
system
to permit
Prio r Postpartu
Margolius
et al.
Postpartum
Second
(Days)
ab
Walpot
Normal
VIII
many
as the husband’s
have
to postulate
Resulting
Remission
at
Delivery
Delivery
(Sex
No
32
90
of Child)
Recurrence
t
Normal
41
Yes
Normal
90
25
No
Normal
270
20
Yes
Normal
(male)
No
(?)
90
Normal
29
No
II
Therapeutic
ab-3rd
Normal
60
26
Yes
month
Normal
No
(Female)
Normal
7
No
(?)
Normal
None
25
not
V III Inhibitors
(?)
196425
have
induces
a change
in the
it to recognize
these
allo-
m Factor
Pregnancy
0
Normal
6 NI deliv
24
appears
is that
In
Pregnancy
Child)
factor
(?)
1 96 1 24
a review
33 reported
in 1 2 and of
therapy
the same response
would
therefore
(?)
None
27
et al.
in fact
from
that
donors
factor
(?)
196124
female
(?)
None
20
case,
to replacement
(male)
195723
hypotheinhibitors
anticipate
Age at
4 NI deliv
195322
pregnancy
with
that
of the
was reported
1 NI deliv
194921
original
If the allotypic
expect
that
no evidence
One might
Symptoms
Spont
the
last objecthe patient
been a problem
in this disorder;2
there was
of such a response
in our patient
either.
in Patie nts With
of
This
since
pregnancies
literature
revealed
the sex of the child
Implicated
(Sex
from
during
Timeto
Year
steroids
since factor
VIII is coded
for on the X chroand thus paternal
transmission
of an X chrowould
result
in the fetus being female.
While
anamnestic
concentration
of Second
was taking
these 7 were males.
Another
observation
that
to be at variance
with the allotypic
hypothesis
caution,
however,
since: ( I ) while the differences
were
statistically
significant,
they
were
not dramatically
different,
(2)
whole
plasmas
rather
than
purified
factor
months
now pregnant
again.
correct,
one would
only
this
reasonable
hemophilic,
or von
must be interpreted
(4) the patient
or pooled
normal
plasma.
not be of great consequence
many
and was
sis were
incorporated
more
3H-thymidine
into
incubated
in the presence
of her husband’s
than her own,
These
studies
used,
AL.
at the time of the first assays,
(5) the responses
in the
presence
of von Willebrand
and hemophilic
plasma
at
23 mo did
not
differ
from
those
employing
the
DISCUSSION
activity,’2
was
ET
2
28
Yes
Normal
(?)
No
Premature
(?)
l977
Voke and Letsky
33
None
Normal
20
33
Yes
Normal
(?)
Also reported
by Conley et a 1.27 and Margolius
B1eeding
symptoms
pregnancy or delivery.
The
patient
had
were
present
a partial
clinical
subcutaneous
hemorrhages
and persisted
for 4 1 days.
§The
inhibitor
was present
occurred
before
remission
at the onset
et al.24
second
2 wk before
Noll
(?)
prior
term.
of the second
pregnancy
and
to the
second
The delivery
pregnancy
reappeared
pregnancy.
was
uneventful
and diminished
within
The
several
early
after
pregnancy
but profuse
and finally
weeks
hemorrhage
disappeared
delivery.
was
but
uneventful,
occurred
before
apparently
but
not
during
gross
hematuria
and
on the second
postpartum
day
delivery.
IImere
was no excessive bleeding associated with the abortion. but persistent menometrorrhagia
began soon thereafter.
#{182}The
inhibitor was present at the onset of the second pregnancy,
diminished in titer during the pregnancy
and disappeared
4
wk before
delivery.
the
completely
approximately
From www.bloodjournal.org by guest on August 11, 2017. For personal use only.
POSTPARTUM
FACTOR
typic changes
transplacental
sensitization.
ance with
VIII
INHIBITOR
or that there
as compared
Our
what
hypothesis.
VIII:
CAg
623
is something
unique
to the
to the intravenous
route of
VIII:CAg
results
would
be expected
Although
assay
has
a difference
only been
are
from
and
also at vanthe allotypic
in the
identified
reviewof
A
the
literature
eight
patients
pregnant
again
resulted
slope of the
in a single
to
her
inhibitor.
Interestingly,
actually
had the inhibitors
second
pregnancies
but
identifica-
our own
occurrence
the
postpartum
factor
VIII inhibitor
five were
in remission
at the
delivery
and none of these patients
continued
the second
cases,
we
in the
in addition
following
who
of a
(Table
3). Of these,
time
of the second
had a recurrence
of
pregnancies.
pregnancies
cases
of women
with
With
our case,
were uneventful
postpartum
that
in
factor
VIII
inhibitors
delivery.
who were free of the inhibitor
We do not know of any cases
at the time of
in this category
in which
relapse
also
evidence
would
mately
did occur.
This
interesting
to respond
to note that after
less well to their
pregnancy
husband’s
mixed
lymphocyte
culture.’8”9
accentuated
with
increasing
some active form of immunologic
In conclusion,
would
pregnancies
be taken
as
women
appear
lymphocytes
in
Since
this
effect
is
parity,
it suggests
that
tolerance
is involved.
while the pathogenesis
appear
that the prognosis
in patients
with postpartum
inhibitors
is likely
complete
remissions.
to decrease
and finally
disappeared
before
delivery.
In addition
to these eight reported
have been able to learn
of three
additional
might
against
the allotypic
hypothesis
since
one
expect
subsequent
sensitization
by approxihalf of the second
daughters.
However,
it is
tam,it
two
of these
patients
present
at the onset of their
their
antifactor
VIII
titers
cases
by personal
communications
with other
gators’57
wherein
patients
with
postpartum
VIII
inhibitors
subsequently
became
pregnant
uneventful
subsequent
all nine
hemophilic
patient,28
a marked
difference
in antigenic
structure
might
possibly
lead to the recognition
of a
change
in the assay slope when plasmas
of the patient,
her husband,
or child
are compared.
No such differences were observed.
tion of
became
had
meansthat
to be favorable
remains
uncerfor subsequent
factor
VIII
in those
achieving
ACKNOWLEDGMENT
We
investifactor
again
would
Hartnett,
Jennifer
like
to
thank
and
Carl
Carta
Floyd
and
Vesta
Dorene
Turi,
Penny
for outstanding
Carucci
for
Hausser,
technical
outstanding
James
assistance
and
secretarial
assis-
tance.
REFERENCES
I.
Shapiro
SS,
coagulation
2.
Hultin
factors.
Michiels
inhibitor
ii,
4.
Kasper
Green
more
CK,
uniform
VIII
antibodies:
Blood
6. Coller
detection
nologic
pH.
ME,
8. Lazarchick
factor
Further
BR
Jr.
Blood
and
van
Eys
Thromb
55,
Yount
Wi:
immunochemical
Gralnick
HR:
A new
MB,
for
A
T,
by combined
procoagulant
AHF)
Platelet
52:69,
10.
EJW,
R, Rizza
18.
Jenkins
paternal
LW:
Immunoradiometric
antigen.
J Clin
54:335,
of immuAm
J
adhesiveness
1969
Coller
CA
Jr.
Thompson
in von Willebrand’s
20.
JH
Jr.
Didisheim
MB.
Reversible
system
P:
CR:
during
pregnancy
cultures.
J Immu-
during
gestation.
Semin
to molecular
NY
Acad
biology
of factor
Sci 240:370,
1975
Personal
communication
communication
Hancock
KW:
Maternal
antigens
unresponsiveness
in human
to
pregnancy.
Trans-
aspects
Obstet
of immuGynecol
1972
1979
E,
protein
Med
Frick
transplacental
West
R:
of blood.
iS, Haden
34:151,
PG:
The
Chem
significance
of
the
I 66: 189, 1946
RL: Hemophilia-like
disease in women.
1949
Hemophilia-like
transfer
biological
J Biol
of
an
disease
acquired
Blood 8:598,
decrease
Zbinden
J, Leopold
R:
Schwiez Med Wochenschr48:1478,
reten-
I.
21:179,
communication
disease. Am J Clin Pathol
in platelet
plasma
leukocyte
approach
Personal
DM,
Chargaff
LabClin
62:1048,
23.
BS, Zucker
lM:
13:618,
21 . Hewlett
measurement
Invest
substances.
Transplantation
19. Gleicher
N, Deppe G, Cohen
CJ: Common
nologic
tolerance
in pregnancy
and malignancy.
Carrier
activities.
immune
histocompatibility
plantation
of plate-
of mixed
of the molecule.
A: Personal
dependence
in maternal
J: Clinical
thromboplastic
procoagulant
Owen
Lazerson
heterogeneity
Lurie
22.
Bowie
Maternal
Biggs
D-B:
action.
1977
17.
biologi-
I978
9.
SA:
1:119,
16.
measurement
(VIII
Gail
Perinatol
and
theoretical
Laurent
of
the
1971
Nilsson
maintenance
by disturbing
1971
immunosuppressive
range
5: A factor
15.
pH
induced
I 36:769,
the reactivity
nol 107:1296,
14.
Diath
1976
Moore
Kasakura
Heterogene-
aggregation:
device
47:841,
The
and
suppresses
13.
PH,
I:
1976
J, Hower
VIII
J,
J, Levine
NR,
inhibitors.
platelet
hemophilia
AGN)
Clin Pathol 65:975,
the
VIII
Fratantoni
Med
F: Serum-derived
purification
12.
1977
Jones
in classic
(VIII
JR.
Lazerson
Shulman
FS, Shapiro
implications.
plasma
Edson
(adhesiveness)
Biol
I 976
semi-
prepared
that
MW,
ristocetin-induced
practical
Eyster
Franza
A
columns
Exp
Soc
I I . Miller
VIII
VIII:
49:807,
BS,
of quantitative
CF.
bead
Proc
Partial
a commercially
RB,
55,
offactor
London
J: Factor
by glass
blood.
1978
Abildgaard
Counts
Shapiro
MB,
tion
blood
Abels
PM,
with
the
1975
1967
Hilgartner
JG,
1975
ity of factor
7.
JW,
Pool
measurement
cal studies.
let-rich
LM,
to
1:336,
20:97,
assay
59:706,
34:869,
5. Hultin
of
Med
Plas
J,
VIII
Aledort
CW,
Haemorrh
and
Clin
D, Hampton
McMillan
van der
J Haematol
factor
J Lab
inhibitors
Hemostas
Vanderherden
automaticone-stage
standard.
Li,
Scand
JV,
Acquired
Thromb
Bosch
postpartum.
3. Simone
M:
Semin
following
circulating
pregnancy,
anticoagulant.
1953
Uber
Hemmkorperhamophilie.
1957
with
J
From www.bloodjournal.org by guest on August 11, 2017. For personal use only.
COLLER
624
24.
Margolius
coagulants:
A
Medicine
25.
agulans.
26.
A Jr. Jackson
study
40:145,
Walpot
of
Clin Pathol
DP,
cases
Ratnoff
and
OD:
a review
Circulating
of
the
27.
anti-
30:928,
CL, RatnoffOD,
of blood
ing the activation
L: Verworven
J, Letsky
Conley
on the initiation
literature.
1961
NedTijdschrGeneesk
Voke
40
hemofilie
108:127,
E: Pregnancy
1977
door
and
een circulerend
antico-
28.
to factor
VIII.
of a plasma
CE, Hartmann
II.
RD: Studies
An anticoagulant
thromboplastic
factor.
inhibit-
J Clin
Invest
29:1 182, 1950
1964
antibody
Ellicott
coagulation.
ET AL.
J
agulant
Peake
IR,
factor-VIll
in haemophilia.
Bloom
AL:
antigen
Lancet
1:473,
Immunoradiometric
in plasma
1978
assay
of proco-
and serum and its reduction
From www.bloodjournal.org by guest on August 11, 2017. For personal use only.
1981 58: 619-624
Normal pregnancy in a patient with a prior postpartum factor VIII inhibitor:
with observations on pathogenesis and prognosis
BS Coller, MB Hultin, LW Hoyer, F Miller, JV Dobbs, MH Dosik and ER Berger
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