te a fait grimper la num&ation pla- Case report
ROBERT J. ADDERLEY, * MD, FRCP[C]
PAUL C.J. RoGERs,t MB, MRCP,
FRCP [C]
DOROTHY SHAW,. MB, FRCP [CI
Louis D. WADSWORTH,§ MB, FRCP [C]
A 15-year-old girl with a 9-year
history of idiopathic thrombocyto-
penic purpura resistant to high-dose
steroid therapy and to splenectomy
was admitted to hospital at 35
weeks' gestation with a platelet
count of 10 X 10'/L. The bleeding
time was normal, and measures of
platelet aggregation were nearly so.
Treatment with high intravenous
doses of polyvalent immune globulin
led to a rise in the platelet count to
more than 110 X 10'/L within 5
days. An elective cesarean section
was performed through the lower
uterine segment with good hemosta-
sis. After delivery the platelet count
fell to its former level, but no post-
partum bleeding occurred. There was
a brief episode of thrombocytopenia
in the infant, with some petechiae
but no other hemorrhagic manifesta-
tions. No untoward effects of the
immune globulin infusion were ob-
served in either mother or daughter.
Une jeune fille de 15 ans ayant des
ant&c.dents de 9 ann.es de purpura
thrombocytopenique essentiel r.sis-
tant aux st.roYdes . fortes doses de
m.me qu'.i la spl.nectomie a .t&
admise . l'h6pital . 35 semaines de
gestation alors que sa numeration
plaquettaire .tait de 10 X 10'/L.
Son temps de saignement .tait nor-
mal, et les mesures de l'agr.gation
plaquettaire l'.taient presque. L'ad-
ministration intraveineuse de fortes
doses d'immuno-globuline polyvalen-
From the departments of *tpediatrics, t§pa-
thology and 4obstetrics, University of British
Columbia, the Children's Hospital and the
Salvation Army Grace Hospital, Vancouver
Reprint requests to: Dr. Paul C.J. Rogers,
Department of pediatrics, Children's Hospi-
tal, 4480 Oak St., Vancouver, BC V6H 3V4
894 CAN MED ASSOC I, VOL. 130, APRIL 1, 1984
quettaire . plus de 110 X 10'/L en 5
jours. Une c.sarienne &lective a
pratiqu&e par le segment ut&in in-
ferieur sous bonne h&mostase. Apr.s
l'accouchement la num&ation pla-
quettaire est retomb& i. son niveau
ant.rieur, mais il n'y a pas eu
d'h&morragie du post-partum. On a
observe chez le b.b. un bref &pisode
de thrombocytop.nie avec l'appari-
tion de quelques p.t&hies, mais il
n'y a pas eu d'autres manifestations
h.morragiques. Aucun effet nuisible
attribuable . la perfusion d'immuno-
globuline n'a &t. observe, ni chez la
mere ni chez la fille.
The pregnancy and delivery of a
patient with severe idiopathic
thrombocytopenic purpura (ITP)
carries risks for both mother and
child and poses problems for the
obstetrician, neonatologist and he-
matologist.' Despite the availability
of sophisticated obstetric care, ste-
roid therapy and platelet concen-
trates, there are still rare reports of
maternal death,2 and there continues
to be a greater than normal inci-
dence of postpartum bleeding.'2
Splenectomy performed during
pregnancy is associated with an in-
creased frequency of both abortion
and maternal death. In the neonatal
period the infants may have bleed-
ing tendencies, the most severe con-
sequence of which can be intraven-
tricular hemorrhage, that contribute
to increased morbidity and mortali-
ty.
Recent reports on the use of phar-
macologic doses of immune globulin
(mainly IgG) given intravenously in
both children and adults with auto-
immune thrombocytopenic purpura
have shown a transient, though oc-
casionally prolonged, rise in the
platelet count.36
We report a case of chronic ITP
in which the intravenous infusion of
immune globulin may have con-
tributed to a safe cesarean section
and postpartum course.
Clinical history
A 15-year-old girl presented with
nausea, fatigue, gingival bleeding
and an abdominal mass. The plate-
let count was 11 X 10'/L. Abdomi-
nal ultrasound scanning revealed a
fetus of 21 weeks' gestation.
ITP had been diagnosed when she
was 6 years old during treatment in
hospital for a fractured tibia. Her
response to both steroid therapy and
subsequent splenectomy had been
poor. At 12 years of age, when her
platelet count was 13 X 1 0'/L and
the results of testing for antinuclear
and anti-DNA antibodies were neg-
ative, examination of a bone marrow
specimen had shown a hypercellular
marrow with megakaryocytic hyper-
plasia; a liver-spleen scan with tech-
netium 99m sulfur colloid had not
demonstrated an accessory spleen.
At 32 weeks' gestation the pa-
tient's platelet count was 10 X 1 0'/L
and prednisone, 100 mg daily, was
given, but there was no improve-
ment. At 35 weeks' gestation she
was admitted to hospital with pete-
chiae and epistaxis.
On the second hospital day uter-
ine contractions began; an infusion
of isoxsuprine was begun, and eight
units of platelets were administered.
After 1 hour the platelet count had
risen to 40 X 10'/L. Preparations
were made for an emergency cesare-
an section. However, labour ceased
during the night. Polyvalent immune
globulin (Gamimune), 12.5 g, was
administered intravenously on each
of the next 5 days, for a total dose of
.1 g/kg. The platelet count peaked,
at 116 X 1 091L, on the eighth hospital
day. On the ninth day the template
bleeding time was normal, at 5 min-
utes, and platelet aggregation
showed only a minor abnormality.
On the 10th day, with the platelet
count at 90 X 1 09/L, an elective
cesarean section was performed
through the lower uterine segment
under general anesthesia, with good
hemostasis. Immediately postopera-
tively the platelet count was 69 X
1 09/L, and it subsequently fell to
preinfusion levels (Fig. 1), but no
postpartum bleeding occurred.
The 2800-g infant had petechiae
scattered over her thorax, and the
platelet count in the cord blood was
44 X 109/L. The platelet count fell
steadily over the next few days, and
prednisone, 2 mg/kg, was adminis-
tered daily when the count 'fell
below 20 X 1 09/L. The count rose
gradually, and at the time of dis-
charge it was 121 X 109/L.
Mother and daughter were dis-
charged on the mother's 33rd hospi-
tal day. Both were well. No unto-
ward effects of the immune globulin
therapy were observed.
Laboratory investigations
Initially, the mother's serum con-
centrations of IgG, IgA, 1gM, C3
and C4 were normal, as were the
proportions of T and B lymphocytes,.
which were measured by rosette for-
mation with sheep erythrocytes and
fluorescence microscopy with sur- fluorescent antibody technique.7 The
face immunoglobulins. Assessment IgG levels in the cord blood (5.70
of the T-cell subsets with the use of g/L) and in the infant's serum when
the monoclonal antibodies OKT4 she was 13 days old (6.20 g/L) were
and OKT8 (Ortho Pharmaceutical normal for her age.8
[Canada] Ltd., Don Mills, Ont.) Our patient's platelet function
showed a reduction in the proportion was assessed before she gave birth,
of 14 (helper) cells to 18% (normal- when the platelet count was near its
ly 45% to 55%) and an increase in peak (Table I). The template bleed-
the proportion of T8 (suppressor) ing time was then normal, and there
cells to 35% (normally 20% to 30%). were no major abnormalities of
No direct or indirect platelet anti- platelet aggregation, but a mild type
bodies were found in the mother's of "release" defect was observed in
blood or in the cord blood with a testing with adenosine diphosphate
Table I-Platelet function in pregnant girl with idiopathic thrombocytopenic purpura
(ITP), in her newborn infant, and in the normal newborn infant of a woman without ITP
Substance; platelet aggregation response, %
Adenosine Arachidonic
diphosphate Ristocetin Epinephrine acid Collagen
Subject (2.5 MM) (1.5 mg/mL) (5.5 gM) (0.5 mg/mL) (0.8 .g/mL)
Mother with ITP* 48 77 75 33 63
Infantt 22 56 15 0 5
Infant of normal
mothert 21 83 7 63 3
Normal values 65-93 72-100 66-89 69-89 65-89
*The mother's blood was sampled after immune globulin had been administered, before she
gave birth, when the platelet count had risen to 108 X 10'/L.
tThe cord blood was sampled; both infants were delivered by elective cesarean section.

200 Infusion
of immune globulin
-J
II III
o 150
.1
Cesarean 20
,.sectlon
--I
18 __
.100 /
16.
-I.-, /

w
Platelet I
/ 14 .
transfusion
I
. _
12.

10
10 -,
8
13579111315171921
Days in hospital
and arachidonic acid. There was no
aggregation of the cord blood plate-
lets with arachidonic acid, compared
with a 63% response in the cord
blood from a control infant born by
elective cesarean section on the
same day. The other measures of
platelet aggregation in the two in-
fants we?re similar.
Discussion
The dramatic rise in our patient's
platelet count produced by the infu-
sion of immune globulin was not as
high or as sustained as in 10 of 11
nonpregnant patients previously de-
scribed.3'4 The response may have
been lessened by the concomitant
administration of steroids, by the
fact that the patient's disease had
been refractory to both high-dose
steroid therapy and splenectomy, or
by some effect of the pregnancy
itself.
However, the response of our pa-
tient's platelet count was similar to
that reported for several other preg-
nant women with ITP who received
high doses of immune globulin intra-
venously. Wenske and coworkers9
reported on two patients whose
platelet counts had risen directly
after such an infusion. Platelet-
associated immunoglobulins were
detected in their blood but were not
demonstrable in the serum of our
patient. Both of their infants had
platelet counts within the normal
range, but in one the count dropped
rapidly in association with an in-
crease in the level of platelet-
associated immunoglobulin. This in-
fant received immune globulin intra-
venously, and the platelet count re-
sponded favourably. The report by
Morgenstern and associates'0 is less
convincing: the maternal platelet
count rose only on the first day
following delivery and completion of
the immune globulin infusion. The
infant's platelet count was normal.
In these three previous cases the
immune globulin administered to
the pregnant women apparently
crossed the placenta, as was shown
by their infants' normal platelet
counts at birth.9"0 This may have
happened in our case, too, though to
a minor degree, since this infant's
platelet count dropped after birth.
However, the child's serum im-
munoglobulin levels were no higher
than was normal for her age.
896 CAN MED ASSOC J, VOL. 130, APRIL 1, 1984
All immune globulin currently
marketed for use in infants has been
modified in some fashion to render
it suitable for intravenous infusion.
This modification may have affected
the transplacental transfer of im-
munoglobulin between our patients.
Membrane receptors on the placenta
that are specific for IgG mediate the
active transport of this immuno-
globulin from mother to fetus."'3 A
normal conformation of the IgG
molecule, with an intact Fc region,
may be necessary for it to bind to its
receptor site and cross the placental
barrier. Alternatively, there may
have been insufficient time between
the infusion of immune globulin and
delivery for a significant amount of
IgG to have been transferred to the
fetal circulation.
The mechanism by which the in-
travenous administration of immune
globulin produces a rise in the plate-
let count of patients with ITP re-
mains unclear. Fehr and collabora-
tors4 suggested that the commercial
preparations interfere with phago-
cytic Fc-receptor-mediated immune
clearance.
In those rare patients who have
very low platelet counts secondary
to ITP and who are unresponsive to
treatment with steroids the infusion
of supraphysiologic doses of immune
globulin to temporarily increase the
platelet count may allow for a safe
delivery and puerperium. Immune
globulin infusions in the pregnant
patient may also have an effect, if
only slight, on neonatal throm-
bocytopenia. The cost of this treat-
ment is prohibitive for generalized
use, and further experience and tri-
als are needed before this therapy
can be recommended for use during
pregnancy.
We thank Drs. Sheldon C. Naiman,
Aubrey J. Tingle and Vijendra K. Singh
for their expert technical assistance and
advice.
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