ACOG
PRACTICE
This Practice Bulletin was
developed by the ACOG Com-
mittee on Practice Bulletins
Obstetrics with the assistance
of Robert M. Silver, MD,
Richard L. Berkowitz, MD, and
James Bussel, MD. The infor-
mation is designed to aid prac-
titioners in making decisions
about appropriate obstetric and
gynecologic care. These guide-
lines should not be construed as
dictating an exclusive course of
treatment or procedure.
Variations in practice may be
warranted based on the needs
of the individual patient,
resources, and limitations
unique to the institution or type
of practice.
Reaffirmed 2014
BULLETIN
CLINICAL MANAGEMENT GUIDELINES FOR
OBSTETRICIANGYNECOLOGISTS
NUMBER 6, SEPTEMBER 1999
Thrombocytopenia
in Pregnancy
Thrombocytopenia in pregnant women is diagnosed frequently by obstetricians
because platelet counts are now included with automated complete blood cell
counts (CBCs) obtained during routine prenatal screening (1). The condition is
common, occurring in 78% of pregnancies (2). Thrombocytopenia can result
from a variety of physiologic or pathologic conditions, several of which are
unique to pregnancy. Some causes of thrombocytopenia are serious medical
disorders that have the potential for profound maternal and fetal morbidity. In
contrast, other conditions, such as gestational thrombocytopenia, are benign
and pose no maternal or fetal risks. Because of the increased recognition of
maternal and fetal thrombocytopenia, there are numerous controversies regard-
ing obstetric management. Clinicians must weigh the risks of maternal and
fetal bleeding complications against the costs and morbidity of diagnostic tests
and invasive interventions.
Background
Platelet Function
Unlike other bleeding disorders in which bruising often is the initial clinical
manifestation, platelet disorders, such as thrombocytopenia, usually result in
bleeding into mucous membranes. Although bruising can occur, the most com-
mon manifestations of thrombocytopenia are petechiae, ecchymoses, epistaxis,
gingival bleeding, and menometrorrhagia. In contrast to hemophilia, bleeding
into joints usually does not occur; life-threatening bleeding is less common but
can occur, resulting in hematuria, gastrointestinal bleeding, and, although rare,
intracranial hemorrhage.
Definition of Thrombocytopenia
The normal range of the platelet count in nonpregnant
individuals is 150,000400,000/L. In this population,
thrombocytopenia is defined as any platelet value less
than 150,000/L, with counts of 100,000150,000/L
indicative of mild thrombocytopenia, 50,000100,000/L
indicative of moderate thrombocytopenia, and less than
50,000/L indicative of severe thrombocytopenia. The
definition of thrombocytopenia is somewhat arbitrary and
not necessarily clinically relevant. Clinically significant
bleeding usually is limited to patients with platelet counts
less than 10,000/L. Serious bleeding complications are
rare, even in those with severe thrombocytopenia (3).
Excessive bleeding associated with trauma or surgery is
uncommon unless the patients platelet count is less than
50,000/L. The mean platelet count in pregnant women is
lower than in nonpregnant individuals (4, 5).
Differential Diagnosis of
Thrombocytopenia
Thrombocytopenia is due to either increased platelet
destruction or decreased platelet production. In pregnan-
cy, the former is responsible for most cases (2). Increased
platelet destruction can be caused by an immunologic
destruction, abnormal platelet activation, or platelet con-
sumption resulting from excessive bleeding or exposure
to abnormal vessels. Decreased platelet production is less
common, and usually is associated with either leukemia,
aplastic anemia, or folate deficiency (6, 7).
The most common cause of thrombocytopenia dur-
ing pregnancy is gestational thrombocytopenia, which
accounts for about two thirds of cases (2) (see the box).
Gestational Thrombocytopenia
Gestational thrombocytopenia, also termed essential
thrombocytopenia or benign or incidental thrombocy-
topenia of pregnancy, is by far the most common cause of
mild thrombocytopenia during pregnancy, affecting up to
8% of gestations (2). There are several characteristics of
this condition (2). First, the thrombocytopenia is relative-
ly mild with platelet counts usually remaining greater
than 70,000/L. However, a lower threshold for gesta-
tional thrombocytopenia has never been established.
Second, women are asymptomatic with no history of
bleeding. The thrombocytopenia usually is detected as
part of routine prenatal screening. Third, women have no
history of thrombocytopenia prior to pregnancy (except in
previous pregnancies). Although gestational thrombocy-
topenia may recur in subsequent pregnancies (8), the
recurrence risk is unknown. Fourth, platelet counts usual-
ly return to normal within 212 weeks following delivery.
2 ACOG Practice Bulletin No. 6
Causes of Thrombocytopenia in Pregnancy
Gestational thrombocytopenia
Pregnancy-induced hypertension
HELLP syndrome
Pseudothrombocytopenia (laboratory artifact)
Human immunodeficiency virus (HIV) infection
Immune thrombocytopenic purpura
Systemic lupus erythematosus
Antiphospholipid syndrome
Hypersplenism
Disseminated intravascular coagulation
Thrombotic thrombocytopenic purpura
Hemolytic uremic syndrome
Congenital thrombocytopenias
Medications (heparin, quinine, quinidine,
zidovudine, sulfonamides)
Finally, there is an extremely low risk of fetal or neonatal
thrombocytopenia. In a large, prospectively evaluated
cohort study of 756 women with gestational thrombocy-
topenia, only one womans infant had a platelet count of
less than 50,000/L (9). However, this infant had throm-
bocytopenia due to congenital bone marrow dysfunction.
Another study confirmed the extremely low risk of fetal
thrombocytopenia in women with gestational thrombocy-
topenia (10). Thus, women with gestational thrombocy-
topenia are not at risk for maternal or fetal hemorrhage or
bleeding complications.
Although its cause is uncertain, gestational thrombo-
cytopenia may be due to accelerated platelet consumption
(4). Antiplatelet antibodies often are detectable in women
with gestational thrombocytopenia, but neither their pres-
ence nor their absence can be used to diagnose the disorder
or differentiate it from immune thrombocytopenic purpura
(ITP) (11). Indeed, there are no specific diagnostic tests to
definitively distinguish gestational thrombocytopenia from
mild ITP (1). The primary means of differentiation is to
monitor platelet counts closely, to look for levels that
decrease below the 50,00070,000/L range, and to docu-
ment a normal neonatal platelet count and a restoration of
normal maternal platelet values after delivery.
Thrombocytopenia with an
Immunologic Basis
Thrombocytopenia with an immunologic basis during
pregnancy can be broadly classified as two disorders:
neonatal alloimmune thrombocytopenia and ITP, an
autoimmune condition. Neonatal alloimmune thrombocy-
topenia has no effect on the mother but probably is respon-
sible for more intracranial hemorrhage due to thrombocy-
topenia than all the other primary thrombocytopenic
conditions combined. In contrast, ITP may affect both
mothers and fetuses, but with appropriate management the
outcome for both is excellent.
Neonatal Alloimmune Thrombocytopenia
Neonatal alloimmune thrombocytopenia is the platelet
equivalent of hemolytic (Rh) disease of the newborn,
developing as a result of maternal alloimmunization to
fetal platelet antigens. It affects one in 1,0002,000 live
births and can be a serious and potentially life-threatening
condition (12, 13). Unlike Rh disease, neonatal alloim-
mune thrombocytopenia can occur during a first pregnan-
cy. Almost half of the clinically evident cases of neonatal
alloimmune thrombocytopenia are discovered in the first
live-born infant (14).
In typical cases of unanticipated neonatal alloimmune
thrombocytopenia, the mother is healthy and has a normal
platelet count, and her pregnancy, labor, and delivery are
indistinguishable from those of other low-risk obstetric
patients. The neonates, however, are either born with evi-
dence of profound thrombocytopenia or develop sympto-
matic thrombocytopenia within hours after birth. Affected
infants often manifest generalized petechiae or ecchy-
moses over the presenting fetal part. Hemorrhage into vis-
cera and bleeding following circumcision or venipuncture
also may ensue. The most serious complication of neona-
tal alloimmune thrombocytopenia is intracranial hemor-
rhage, which occurs in 1020% of infants (14, 15). Fetal
intracranial hemorrhage due to neonatal alloimmune
thrombocytopenia can occur in utero, and 2550% of fetal
intracranial hemorrhage in untreated mothers may be
detected by ultrasonography before the onset of labor (16).
Ultrasonographic findings may include intracranial hem-
orrhage, porencephalic cysts, and obstructive hydro-
cephalus. These observations are in contrast to neonatal
intracranial hemorrhage due to ITP, which is exceedingly
rare and usually occurs during the neonatal period.
Several polymorphic, diallelic antigen systems resid-
ing on platelet membrane glycoproteins are responsible
for neonatal alloimmune thrombocytopenia. Many of
these antigen systems have several names because they
were identified in different parts of the world concurrent-
ly. Recently, a uniform nomenclature has been adopted
that describes these antigens as human platelet antigens
(HPA-1 and HPA-2), with alleles designated as a or b
(17). Although there are at least 10 officially recognized
platelet-specific antigens at this time, more than 50% of
ACOG Practice Bulletin No. 5
the reported cases in Caucasians and most of the severe
cases have occurred as a result of sensitization against
HPA-1a, also known as PlA1 and Zwa.
Fetal thrombocytopenia due to HPA-1a sensitization
tends to be severe and can occur early in gestation. In a
cohort study of 107 fetuses with neonatal alloimmune
thrombocytopenia (97 with HPA-1a incompatibility)
studied in utero before receiving any therapy, 50% had
initial platelet counts of less than 20,000/L (13). This
percentage included 21 of 46 fetuses tested before 24
weeks of gestation. Furthermore, this series documented
that the fetal platelet count decreases at a rate of more
than 15,000/L per week in the absence of therapy.
The recurrence risk of neonatal alloimmune throm-
bocytopenia is extremely high and approaches 100% in
cases involving HPA-1a if the subsequent sibling carries
the pertinent antigen (13). Thus, the recurrence risk is
related to the zygosity of the father. As with red cell
alloimmunization, the disease tends to be equally severe
or progressively worse in subsequent pregnancies.
Immune Thrombocytopenic Purpura
Acute ITP is a self-limited disorder that usually occurs in
childhood. It may follow a viral infection and rarely per-
sists. Chronic ITP typically occurs in the second or third
decade of life and has a female to male ratio of 3:1 (18).
Estimates of the frequency of ITP during pregnancy vary
widely, affecting one in 1,00010,000 pregnancies (19).
Immune thrombocytopenic purpura is characterized
by immunologically mediated platelet destruction. The
patient produces IgG antiplatelet antibodies that recog-
nize platelet membrane glycoproteins. This process leads
to increased platelet destruction by cells of the reticu-
loendothelial system (18). The rate of destruction
exceeds the compensatory ability of the bone marrow to
produce new platelets, which leads to thrombocytopenia.
Most of the platelet destruction occurs in the spleen,
although other sites also are involved.
There are no pathognomonic signs, symptoms, or
diagnostic tests for ITP; it is a diagnosis of exclusion.
However, four findings have been traditionally associat-
ed with the condition: 1) persistent thrombocytopenia
(platelet count <100,000/L with or without accompany-
ing megathrombocytes on the peripheral smear), 2) nor-
mal or increased numbers of megakaryocytes determined
from bone marrow, 3) exclusion of other systemic disor-
ders or drugs that are known to be associated with throm-
bocytopenia, and 4) absence of splenomegaly.
Most women with ITP have a history of bruising eas-
ily and petechiae, or of possible epistaxis and gingival
bleeding, which precedes their pregnancy, but some
women are completely asymptomatic. Important hemor-
3
rhagic symptoms rarely occur unless the platelet count is
less than 20,000/L. It is believed that the course of ITP
usually is not affected by pregnancy, although there have
been anecdotal reports of patients conditions worsening
during pregnancy and improving postpartum (20, 21).
Pregnancy may be adversely affected by severe thrombo-
cytopenia, and the primary risk to the mother is hemor-
rhage during the peripartum period.
Maternal IgG antiplatelet antibodies can cross the
placenta, placing the fetus and neonate at risk for the
development of thrombocytopenia. Retrospective case
series of ITP in pregnancy indicate that 1215% of
infants born to mothers with ITP will develop platelet
counts less than 50,000/L (22, 23). Sometimes, this
results in minor clinical bleeding such as purpura, ecchy-
moses, or melena. On rare occasions, fetal thrombocy-
topenia associated with ITP leads to intracranial hemor-
rhage unrelated to the mode of delivery. When it occurs,
intracranial hemorrhage can result in severe neurologic
impairment and even death. Serious bleeding complica-
tions are estimated to occur in 3% of infants born to
women with ITP, and the rate of intracranial hemorrhage
is less than 1% (22, 23). These data may overestimate the
risk, as a result of publication bias. In a prospective, pop-
ulation-based study of almost 16,000 pregnancies deliv-
ered at a single center, no infant born to a mother with
ITP suffered intracranial hemorrhage (9). The only three
infants with intracranial hemorrhage had neonatal
alloimmune thrombocytopenia, not ITP. The platelet
count of the affected newborn usually will decrease after
delivery, and the nadir may not be reached for several
days (20).
Pregnancy-Induced Hypertension
Pregnancy-induced hypertension (PIH) is reported to be
the cause of 21% of cases of maternal thrombocytopenia
(9). The thrombocytopenia usually is moderate, and
platelet counts rarely decrease below 20,000/L. Clinical
hemorrhage is uncommon unless the patient develops
disseminated intravascular coagulopathy, but a decreas-
ing maternal platelet count generally is considered a sign
of worsening disease and is an indication for delivery.
In some cases, microangiopathic hemolytic anemia
and elevated liver function tests are associated with
thrombocytopenia in individuals with PIH. Such individ-
uals are considered to have HELLP syndrome.
The cause of thrombocytopenia in women with
severe PIH is unknown. The disease is associated with a
state of accelerated platelet destruction, platelet activa-
tion, increased platelet volume, and increased megakary-
ocyte activity (21). Increased levels of platelet-associated
IgG have been detected in patients with PIH (24).
However, this finding is nonspecific and does not neces-
4 ACOG Practice Bulletin No. 6
sarily imply an immunologic basis for the thrombocy-
topenia. Platelet function also may be impaired in women
with PIH, even if their platelet count is normal. It is note-
worthy that the platelet count may decrease before the
other clinical manifestations of PIH are apparent (25).
The neonates of mothers with PIH are at increased
risk of neonatal thrombocytopenia (2). However, this is
true only for infants born prematurely, and especially
those with growth restriction. Term infants of mothers
with PIH are no more likely to have thrombocytopenia
than are controls. In a study of 1,414 mothers with hyper-
tension, neonatal thrombocytopenia associated with PIH
rarely decreased below 20,000/L and caused no fetal
bleeding complications (9).
Clinical Considerations and
Recommendations
What is the appropriate workup for maternal
thrombocytopenia?
When thrombocytopenia is diagnosed in a pregnant
woman, it is important that the diagnosis be as precise as
possible. The differential diagnosis of thrombocytopenia
in pregnancy includes gestational thrombocytopenia,
pseudothrombocytopenia, HIV infection, drug-induced
thrombocytopenia, PIH, HELLP syndrome, thrombotic
thrombocytopenic purpura, hemolytic uremic syndrome,
disseminated intravascular coagulation, systemic lupus
erythematosus, antiphospholipid syndrome, and congeni-
tal thrombocytopenias. These disorders usually can be
determined on the basis of a detailed medical and family
history and a physical examination, with attention to
blood pressure, splenomegaly, HIV serology, and adjunc-
tive laboratory studies as appropriate.
A CBC and examination of the peripheral blood
smear generally are indicated in the evaluation of mater-
nal thrombocytopenia. A CBC is helpful to exclude pan-
cytopenia. Evaluation of the peripheral smear serves to
rule out platelet clumping that may be associated with
pseudothrombocytopenia. Bone marrow biopsy rarely is
needed to distinguish between inadequate platelet pro-
duction and increased platelet turnover. Numerous assays
have been developed for both platelet-associated (direct)
antibodies and circulating (indirect) antiplatelet antibod-
ies. Although many individuals with ITP will have ele-
vated levels of platelet-associated antibodies and some-
times circulating antiplatelet antibodies, these assays are
not recommended for the routine evaluation of maternal
thrombocytopenia (26). Tests for antiplatelet antibodies
are nonspecific, poorly standardized, and subject to a
large degree of interlaboratory variation (1). Also, gesta-
tional thrombocytopenia and ITP cannot be differentiated
on the basis of antiplatelet antibody testing (11).
If drugs and other medical disorders are excluded,
the primary differential diagnosis in the first and second
trimesters will be either gestational thrombocytopenia or
ITP. It should be noted that although gestational throm-
bocytopenia can occur in the first trimester, it typically
becomes manifest later in pregnancy. In general, in a
woman with no history of thrombocytopenia or the
milder the thrombocytopenia, the more likely she is to
have gestational thrombocytopenia. If the platelet count
is less than 70,000/L, ITP is more likely to be present,
and if the platelet count is less than 50,000/L, ITP is
almost certainly present. During the third trimester or
postpartum period, the sudden onset of significant mater-
nal thrombocytopenia should lead to consideration of
PIH, thrombotic thrombocytopenic purpura, hemolytic
uremic syndrome, acute fatty liver, or disseminated
intravascular coagulation, although ITP can present this
way as well.
When should women with ITP receive medical
therapy?
The goal of medical therapy during pregnancy in women
with ITP is to minimize the risk of bleeding complica-
tions associated with severe thrombocytopenia. Because
the platelet function of these patients usually is normal, it
is not necessary to maintain their counts in the normal
range. There is general agreement that asymptomatic
pregnant women with platelet counts greater than
50,000/L do not require treatment. Also, most authori-
ties recommend treatment in the presence of a platelet
count significantly less than 50,000/L or in the presence
of bleeding. However, the degree of thrombocytopenia in
asymptomatic pregnant women that requires treatment is
somewhat controversial, and consultation from a physi-
cian experienced in these matters should be considered.
Higher counts (eg, >50,000/L) are desirable for invasive
procedures and delivery, which may be associated with
hemorrhage, the need for surgery, or the desire to use
regional anesthesia. Bleeding times are not useful in
assessing platelet function in patients with ITP.
What therapy should be used to treat ITP dur-
ing pregnancy?
The first line of treatment for ITP is prednisone, usually
initiated in a dosage of 12 mg/kg/d. A response to ante-
natal corticosteroids usually occurs within 37 days and
reaches a maximum within 23 weeks. Once platelet
counts reach acceptable levels, the dosage can be tapered
by 1020% per week until the lowest dosage required to
ACOG Practice Bulletin No. 6
maintain a platelet count greater than 50,000/L is
reached. An increase in the platelet count occurs in about
70% of patients, and up to 25% will achieve complete
remission (27).
Intravenous immune globulin (IVIG) is appropriate
therapy for cases refractory to steroids as well as in cir-
cumstances such as platelet counts less than 10,000/L in
the third trimester, or platelet counts less than 30,000/L
associated with bleeding or with preoperative or prede-
livery status. A response to therapy can be expected in as
few as 6 hours or in as many as 72 hours. In 70% of
cases, the platelet count will return to pretreatment levels
within 30 days after treatment (26, 28). Intravenous
immune globulin is costly and of limited availability.
When considering use of IVIG, it is prudent to seek con-
sultation from a physician experienced in such cases.
Splenectomy is associated with complete remission
in approximately 66% of patients with ITP (18); howev-
er, it often is not successful in patients who do not
respond to intravenous immunoglobulin (29). The proce-
dure usually is avoided during pregnancy because of fetal
risks and technical difficulties late in gestation. However,
splenectomy can be accomplished safely during pregnan-
cy, ideally in the second trimester. It is appropriate for
severe cases (platelet counts of less than 10,000/L) that
have failed treatment with antenatal corticosteroids and
IVIG (26).
Platelet transfusions should be used only as a tem-
porary measure to control life-threatening hemorrhage or
to prepare a patient for surgery. The usual increase in
platelets of approximately 10,000/L per unit of platelets
transfused is not achieved in patients with ITP because of
the decreased survival of donor platelets. Thus, 610 U of
platelet concentrate should be transfused. Other drugs
used to treat ITP such as colchicine, azathioprine, vinca
alkaloids, cyclophosphamide, and danazol have potential
adverse fetal effects.
What additional specialized care should
women with ITP receive?
Other than serial assessment of the maternal platelet
count (every trimester in asymptomatic women in remis-
sion and more frequently in thrombocytopenic individu-
als), little specialized care is required. Pregnant women
with ITP should be instructed to avoid nonsteroidal anti-
inflammatory agents, salicylates, and trauma. Individuals
with splenectomies should be immunized against pneu-
mococcus, Hemophilus influenzae, and meningococcus.
If the diagnosis of ITP is made, consultation and ongoing
evaluation with a physician experienced in such matters
is appropriate.
5
 Can fetal or neonatal intracranial hemorrhage
be prevented in pregnancies complicated by
ITP?
It is logical to assume that therapies known to increase
the maternal platelet count in patients with ITP also
would improve the fetal platelet count. However, medical
therapies such as IVIG (30) and steroids (22, 3032) do
not reliably prevent fetal thrombocytopenia or improve
fetal outcome. Because some of these therapies (eg,
IVIG) have not been adequately tested in appropriate tri-
als, there are insufficient data to recommend maternal
medical therapy for fetal indications.
Some investigators have recommended cesarean
delivery to decrease the risk of intracranial hemorrhage
by avoiding the potential trauma associated with vaginal
birth (33). This strategy was based on anecdotal reports
of intracranial hemorrhage associated with vaginal deliv-
ery (34) as well as the biologic plausibility of the hypoth-
esis. Others have proposed that cesarean delivery be
reserved for fetuses with platelet counts less than
50,000/L (35, 36). This tactic was prompted by the
observation that the risk of fetal bleeding is inversely pro-
portional to the platelet count, and bleeding problems are
extremely rare in fetuses with platelet counts more than
50,000/L (31, 37).
Cesarean delivery has never been proven to prevent
intracranial hemorrhage reliably. Several reports indicate
that hemorrhagic complications in infants with thrombo-
cytopenia are unrelated to the mode of delivery (22, 31,
37, 38). In a review of 474 neonates born to mothers with
ITP, 29% of infants born vaginally with thrombocytope-
nia had a bleeding complication, compared with 30%
delivered by cesarean birth (31). In this study, the rate of
intracranial hemorrhage also was similar for both modes
of delivery: 4% after vaginal delivery and 3% after
cesarean delivery. In addition, it is unclear that intracra-
nial hemorrhage is an intrapartum phenomenon. The
neonatal platelet count often dramatically decreases after
delivery. Thus, intracranial hemorrhage during the
neonatal period could be mistakenly attributed to intra-
partum events. No case of intracranial hemorrhage has
been proven definitively to have occurred during labor
(22, 23). Because cesarean delivery does not clearly pre-
vent intraventricular hemorrhage, many obstetricians
choose the mode of delivery in ITP based on obstetric
considerations alone.
What tests or characteristics can be used to
predict fetal thrombocytopenia in pregnancies
complicated by ITP?
No maternal test or characteristic can reliably predict the
severity of thrombocytopenia in all cases of infants born
6 ACOG Practice Bulletin No. 6
to mothers with ITP. Maternal characteristics and serolo-
gy, including prior splenectomy, platelet count, and the
presence of platelet-associated antibodies, all correlate
poorly with neonatal thrombocytopenia (39, 40). Fetal
thrombocytopenia is rare in the absence of circulating
antiplatelet antibodies (10), but exceptional cases have
been reported (41). Also, these assays are difficult to per-
form and have a low positive predictive value (10).
Is there any role for fetal platelet count deter-
mination in ITP?
At this time, most obstetricians do not obtain fetal
platelet counts (42). Scalp sampling is fraught with inac-
curacies and technical difficulties, and cordocentesis car-
ries a 12% risk of necessitating an emergent cesarean
delivery for fetal indications (43). The low incidence of
intracranial hemorrhage and the lack of demonstrated
difference in neonatal outcome between vaginal and
cesarean deliveries also supports the opinion that the
determination of fetal platelet count is unwarranted for
ITP (22, 23, 31, 37, 44). A substantial minority of peri-
natologists (42) feel that the 5% risk of fetal thrombocy-
topenia of less than 20,000/L and the attendant theoret-
ically increased risk of an intracranial hemorrhage war-
rant informing patients of the availability of cordocente-
sis or scalp sampling during labor when choosing mode
of delivery (4547).
What is the appropriate neonatal care for
infants born of pregnancies complicated by
ITP?
Regardless of the mode, delivery should be accom-
plished in a setting where an available clinician familiar
with the disorder can treat any neonatal complications
and have access to the medications needed for treatment.
Can a patient with thrombocytopenia be given
regional anesthesia?
The literature offers only limited and retrospective data
to address this issue. However, two studies (48, 49)
reported on a total of 184 patients with platelet counts
less than 150,000/L. Of these, 113 patients received
epidural anesthesia without neurologic complication or
sequelae. In all of these patients, the diagnosis was ges-
tational thrombocytopenia. Another study of patients
with platelet counts less than 100,000/L due to
preeclampsia, ITP, or infection also received epidural
anesthesia without complication (50). Although the com-
plication of greatest concern is that of epidural
hematoma, there are only two cases in the literature of
parturients who developed an epidural hematoma after
regional anesthesia. One patient had preeclampsia and a
lupus anticoagulant (51) and the other had an ependymo-
ma (52). Cases reported in nonparturients have almost
always been associated with anticoagulant therapy.
Although limited, data support the safety of epidural
anesthesia in patients with platelet counts greater than
100,000/L. In women with gestational thrombocytope-
nia with platelet counts less than 99,000/L but greater
than 50,000/L, epidural anesthesia also may be safe, but
its use in such patients will require a consensus among
the obstetrician, anesthesiologist, and patient. When
platelet counts are less than 50,000/L, epidural anesthe-
sia should not be given.
When should an evaluation for possible
neonatal alloimmune thrombocytopenia be
initiated, and what tests are useful in making
the diagnosis?
The most appropriate screening program incorporates
evaluation of patients with a history of infants with oth-
erwise unexplained bleeding or thrombocytopenia.
Neonatal alloimmune thrombocytopenia should be sus-
pected in cases of otherwise unexplained fetal or neona-
tal thrombocytopenia, porencephaly, or intracranial hem-
orrhage (either in utero or after birth). The laboratory
diagnosis includes determination of platelet type and
zygosity of both parents and the confirmation of maternal
antiplatelet antibodies with specificity for paternal (or
fetalneonatal) platelets and the incompatible antigen.
Platelet typing may be determined serologically or by
genotyping because the genes and polymorphisms
responsible for most cases of neonatal alloimmune
thrombocytopenia have been identified. This is helpful
when the father is heterozygous for the pertinent antigen
because fetal platelet antigen typing can be performed
using amniocytes (53). Chorionic villus sampling should
not be performed because of its potential increased sen-
sitization to antiplatelet antibodies. The laboratory evalu-
ation of neonatal alloimmune thrombocytopenia can be
complex, results may be ambiguous, and an antigen
incompatibility cannot always be identified. Accordingly,
testing for this disorder should be performed in an expe-
rienced regional laboratory that has special interest and
expertise in neonatal alloimmune thrombocytopenia.
There is a theoretical benefit from population-based
screening for platelet antigen incompatibility. However,
such a program has not been shown to be clinically use-
ful or cost-effective and is not currently recommended.
Another area of controversy is the patient whose sister
has had a pregnancy complicated by neonatal alloim-
mune thrombocytopenia. It may be worthwhile to evalu-
ate these patients for platelet antigen incompatibility or
ACOG Practice Bulletin No. 6
human leukocyte antigen phenotype. However, the theo-
retical advantages of testing these women must be
weighed against the potential for anxiety, cost, and mor-
bidity without proven benefit.
How can one determine the fetal platelet count
in pregnancies complicated by neonatal allo-
immune thrombocytopenia?
Unfortunately, as with ITP, there are no good indirect
methods to determine the fetal platelet count. Maternal
antiplatelet antibody titers correlate poorly with the
severity of the disease. Also, characteristics such as the
outcome of previously affected siblings (eg, birth platelet
count or intracranial hemorrhage recognized after deliv-
ery) do not reliably predict the severity of fetal thrombo-
cytopenia (13). Currently, the only accurate means of
estimating the fetal platelet count is to sample the fetal
blood directly, although this may increase the risk of fetal
exsanguination.
What is the appropriate obstetric management
of neonatal alloimmune thrombocytopenia?
The primary goal of the obstetric management of preg-
nancies complicated by neonatal alloimmune thrombocy-
topenia is to prevent intracranial hemorrhage and its
associated complications. In contrast to ITP, however, the
higher frequency of intracranial hemorrhage associated
with neonatal alloimmune thrombocytopenia justifies
more aggressive interventions. Also, strategies intended
to avoid intracranial hemorrhage must be initiated ante-
natally because of the risk of in utero intracranial hemor-
rhage.
The optimal management of fetuses at risk for
neonatal alloimmune thrombocytopenia (those testing
positive for the incompatible antigen or those whose
fathers are homozygous for the antigen) remains contro-
versial. The management decisions for these cases should
be individualized and are best made after consultation
with obstetric and pediatric specialists familiar with the
disorder as soon as the diagnosis is made. Several thera-
pies have been used in an attempt to increase the fetal
platelet count and to avoid intracranial hemorrhage,
including maternal treatment with IVIG, with or without
steroids (15, 5460), and fetal platelet transfusions (59,
61, 62). Intravenous immune globulin administered to the
mother appears to be the most consistently effective
antepartum therapy for neonatal alloimmune thrombocy-
topenia (15). However, none of these therapies is effec-
tive in all cases. Direct fetal administration of IVIG does
not reliably improve the fetal platelet count, although
only a few cases have been reported. Platelet transfusions
7
with maternal platelets are consistently effective in rais-
ing the fetal platelet count. However, the short half-life of
transfused platelets requires weekly procedures and may
worsen the alloimmunization.
It is unknown whether it is necessary to determine
the fetal platelet count before initiating therapy. The risks
of cordocentesis in the setting of neonatal alloimmune
thrombocytopenia must be weighed against the ability to
determine the need for and the effectiveness of therapy.
Although unproven, the benefit of transfusing maternal
platelets at the time of cordocentesis may reduce the risk
of bleeding complications from the procedure (63). The
optimal time during gestation to first assess the fetal
platelet count also is controversial. When fetal blood
sampling is indicated, performance at 2224 weeks of
gestation may optimize medical therapy.
Most investigators recommend determination of the
fetal platelet count once fetal pulmonary maturity is
achieved, but before the onset of labor (eg, 37 weeks of
gestation). A trial of labor is permitted for fetuses with
platelet counts greater than 50,000/L, while those with
severe thrombocytopenia are delivered by cesarean birth.
Although this strategy is of unproven efficacy, the high
rate of intracranial hemorrhage in neonatal alloimmune
thrombocytopenia is considered to warrant these inter-
ventions. Delivery should be accomplished in a setting
equipped to handle a neonate with severe thrombocy-
topenia.
What is appropriate obstetric management for
gestational thrombocytopenia?
Pregnancies with gestational thrombocytopenia are not at
risk for maternal bleeding complications or fetal throm-
bocytopenia (4, 9). Thus, such interventions as the deter-
mination of the fetal platelet count or cesarean delivery
are not indicated in patients with this condition. Women
with gestational thrombocytopenia do not require any
additional testing or specialized care, except follow-up
platelet counts.
Is it necessary to treat thrombocytopenia asso-
ciated with PIH?
The primary treatment of maternal thrombocytopenia in
the setting of PIH or HELLP syndrome is delivery.
Although antepartum reversal of thrombocytopenia has
been reported with medical therapy (64), this course of
treatment is not usual (65, 66). More importantly, the
underlying pathophysiology of PIH will only resolve fol-
lowing birth. Thus, other than to allow for medical stabi-
lization, the effect of betamethasone on fetal pulmonary
maturity, or in special cases at preterm gestations, severe
thrombocytopenia due to PIH is an indication for deliv-
ery (66).
8 ACOG Practice Bulletin No. 6
Major hemorrhage is infrequent in patients with PIH
but minor bleeding such as operative site oozing during
cesarean delivery is common. Platelet transfusions occa-
sionally are needed to improve hemostasis in patients
with severe thrombocytopenia or DIC. However, transfu-
sions are less effective in these women because of accel-
erated platelet destruction. Therefore, platelet transfusions
are best reserved for patients with severe thrombocytope-
nia and active bleeding. An exception is the patient
undergoing cesarean delivery. Although of uncertain ben-
efit, many authorities recommend platelet transfusions to
increase the platelet count to more than 50,000/L before
cesarean delivery (66).
Platelet counts often decrease for 2448 hours after
birth, followed by a rapid recovery (6769). Most
patients will achieve normal platelet counts within a few
days to a week postpartum (67, 69). However, although
rare, thrombocytopenia may continue for a prolonged
period, which often is associated with persistent multi-
system dysfunction (68). Plasma exchange has been
reported to improve the platelet count in women with
HELLP syndrome (70), but the efficacy remains
unproven. Although thrombocytopenia associated with
PIH or HELLP syndrome may improve after treatment
with steroids or uterine curettage (71, 72), the clinical
benefit of these therapies also is uncertain.
Summary
The following recommendation is based on good
and consistent scientific evidence (Level A):
Neonatal alloimmune thrombocytopenia should be
treated with IVIG as the initial approach when fetal
thrombocytopenia is documented.
The following recommendations are based on lim-
ited or inconsistent scientific evidence (Level B):
The mode of delivery in pregnancies complicated by
ITP should be chosen based on obstetric considera-
tions alone. Prophylactic cesarean delivery does not
appear to reduce the risk of fetal or neonatal hemor-
rhage.
Epidural anesthesia is safe in patients with platelet
counts greater than 100,000/L.
Mild maternal thrombocytopenia ( 70,000/L) in
asymptomatic pregnant women with no history of
bleeding problems is usually benign gestational
thrombocytopenia. These women should receive
routine prenatal care with periodic repeat platelet
counts (monthly to bimonthly).
The following recommendations are based primar-
ily on consensus and expert opinion (Level C):
Platelet counts of at least 50,000/L rarely require
treatment.
Neonatal alloimmune thrombocytopenia should be
suspected in cases of otherwise unexplained fetal or
neonatal thrombocytopenia, hemorrhage, or poren-
cephaly.
Prior to initiating any plan of treatment for a woman
based on thrombocytopenia in her fetus, consultation
should be sought from a physician with experience
dealing with that problem.
Laboratory testing for neonatal alloimmune throm-
bocytopenia should be performed in a regional labo-
ratory with special interest and expertise in dealing
with the problem.
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11
 Copyright September 1999 by the American College of
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I Evidence obtained from at least one properly
designed randomized controlled trial.
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trials without randomization.
II-2 Evidence obtained from well-designed cohort or
casecontrol analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
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experience, descriptive studies, or reports of expert
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Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
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12 ACOG Practice Bulletin No. 6