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ITP during pregnancy

Many women with low platelets are concerned about having a family. A low platelet count does not prevent a woman from becoming
pregnant or delivering a fine, healthy baby. However, the situation does require special attention and close coordination between the
womans hematologist, obstetrician, and pediatrician.
Sometimes a low platelet count is discovered when a woman is pregnant. If thats the case, it is important to determine if the low platelet
count is associated with pregnancy (gestational thrombocytopenia) or due to another cause, such as ITP. The journal article, "How I treat
thrombocytopenia in pregnancy" contains information on how to tell if low platelets in pregnancy are due to ITP or some other cause and
the best way to treat the condition.
To diagnose ITP, your doctor may need a:
Physical exam, including a complete medical history. Your doctor will look for signs of bleeding under your skin, and will ask you
about previous illnesses you've had and the types of medications and supplements that you've recently taken.
Complete blood count. This common blood test is used to determine the number of white and red blood cells and platelets in a
sample of your blood. With ITP, white and red blood cell counts are usually normal, but the platelet count is low.
Blood smear. A sample of your blood is placed on a slide and observed under a microscope. This test is often used to confirm the
number of platelets observed in a complete blood count.
Bone marrow examination. Another test that may help identify the cause of a low platelet count is a bone marrow exam. Platelets
are produced in your bone marrow soft, spongy tissue in the center of your large bones. In some cases, a sample of solid bone
marrow is removed in a procedure called a bone marrow biopsy. Or, you may have a bone marrow aspiration, which removes some of
the liquid portion of your marrow. In many cases, both procedures are performed at the same time (bone marrow exam). Both the
liquid and solid bone marrow samples are frequently taken from the same place on the back of one of your hipbones. A needle is
inserted into the bone through an incision.
If you have ITP, your bone marrow will be normal because your low platelet count is caused by the destruction of platelets in your
bloodstream and spleen not by a problem with the bone marrow.
Treatment for ITP during pregnancy
If a woman has ITP and becomes pregnant, her platelet count may drop in the third trimester or she may relapse. However, treatments
such as IVIg or prednisone can be given to raise the platelet count for delivery. Some treatments that are used for ITP, particularly those
that suppress the immune system (except azathioprine) or stimulate platelet production, are not good options for pregnant women
because they could harm the fetus. The thrombopoietin mimetics (TPO agents) are not recommended during pregnancy because they can
cross the placenta. Women should wait up to a year after Rituxan treatments end before becoming pregnant.3 Some studies link prenatal
corticosteroids (ex. prednisone) to mental health problems later in the child's life. 4
Delivery
There is no evidence that a cesarean is safer for the baby in a mother with a low platelet count, so the decision to have a vaginal birth or
cesarean should be based on the best method of delivery given the mothers circumstances.1 Most physicians recommend maintaining a
platelet count above 20,000 to 30,000 platelets per microliter throughout pregnancy and above 50,000 near term. A higher count between
80,000 and 100,000 per microliter would be required for an epidural anesthesia
Only a very small percent of babies born to mothers with ITP have low platelets at birth. Attempting to measure the platelet count of the
fetus carries significant risk, so it is not advised. However, it is fine to do a cord blood count after delivery.2
Breastfeeding
Breastfeeding can be safely accomplished following pregnancies complicated by ITP or gestational thrombocytopenia. There is concern
among some physicians because anti-platelet antibodies can be passed to the newborn in the colostrum of ITP mothers. However, there is
no evidence that children breastfed by ITP mothers are at elevated risk.
Background
Thrombocytopenia is common in mothers and newborns and usually is caused by an increased rate of platelet destruction. The reference
range of a normal plateletcount in nonpregnant women and newborns is 150,000-400,000/L; however, mean platelet counts in pregnant
women generally are lower. Thrombocytopenia in pregnancy has many common causes, including gestational thrombocytopenia, viral and
bacterial infections, and preeclampsia complicated by hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome. This article
focuses on the immune thrombocytopenias, immune thrombocytopenic purpura (ITP) and neonatal alloimmune thrombocytopenia
(NAIT). These relatively rare causes of thrombocytopenia are important, as neonatal outcomes can be significantly impaired and
subsequent pregnancies can be affected. (See images below.)
Pathophysiology
Thrombocytopenia in ITP occurs because of platelet destruction mediated by platelet autoantibodies directed against cell surface
antigens. The reticuloendothelial system destroys platelet/antibody complexes. These autoantibodies can cross the placenta; thus, both
mother and newborn can be affected.
NAIT is caused by maternal immunization against fetal paternally derived platelet-specific antigens (similar to rhesus [Rh] disease). The
mother has a normal platelet count, while the fetus can be severely thrombocytopenic.

Epidemiology
Frequency
United States
The frequency of ITP has been reported to be 1-2 cases per 1000 deliveries in the United States.[1] ITP can be diagnosed during pregnancy,
though, most often, women present for prenatal care with a history of the disorder.
The frequency of NAIT is estimated at 1-2 cases per thousand deliveries
Mortality/Morbidity
Maternal hemorrhage at time of birth is a risk in women with ITP, particularly if the platelet count decreases to less than 20,000/L.
However, no maternal deaths have been reported in the last 20 years,[6] and maternal morbidity is minimal if appropriate therapy is
administered during pregnancy and childbirth. Neonatal thrombocytopenia due to the active transport of antiplatelet antibodies through
the placenta is a clinically more significant problem, and it occurred in 9 of 66 (13.6%) pregnancies complicated by ITP in one review.[7] Of
these infants, 5 of 66 (7.5%) had severe thrombocytopenia, with platelet counts less than 50,000/L. Splenectomy prior to pregnancy was
the only risk factor associated with the development of neonatal thrombocytopenia by logistic regression analysis.
Severe neonatal thrombocytopenia places the infant at risk for intracranial or visceral hemorrhage. None of the 9 thrombocytopenic
infants in the Yamada trial had intracranial hemorrhage documented on clinical neurological examination or ultrasound. Neonatal
intracranial hemorrhage previously has been reported to have a very low incidence (0-2.3%) in newborns of mothers with ITP.[8]
Neonatal morbidity is far more common in NAIT, with 10% of affected newborns dying and 20% experiencing neurological sequelae
secondary to intracranial hemorrhage.[9] Affected infants can have generalized petechiae, hemorrhage into abdominal viscera, and
excessive bleeding after venipuncture or circumcision.
In pregnancy, treatment for ITP and NAIT involves 2 patientsthe mother and the fetus.
In cases of ITP, care of the mother centers on minimizing her risk of bleeding during pregnancy and childbirth. Check platelet counts
regularly throughout gestation to verify that they are in an acceptable range. Conservatively, platelet counts should be checked monthly
during pregnancy (platelet counts should be checked at least every trimester even in completely stable patients). Spontaneous bleeding
seldom occurs if the maternal platelet count is greater than 20,000/L; therefore, treatment is not indicated in the absence of bleeding
unless the platelet count falls below this level. Intraoperative or intrapartum bleeding complications are unusual if the platelet count is
greater than 50,000/L; therefore, administer treatment if the platelet count is less than this prior to delivery.[20] A history of ITP in a
mother or ITP in a previous pregnancy is not a contraindication to future pregnancies.[21]
One trial evaluated the safety of breastfeeding in women with ITP and did not document thrombocytopenia developing in any breastfed
infants.[16] IgG antiplatelet antibodies are transmitted through the breast milk, so consider monitoring the platelet counts in breastfed
newborns of mothers with ITP.
The major neonatal concern in ITP is the risk of fetal or newborn intracranial or visceral hemorrhage due to severe thrombocytopenia.
Newborn thrombocytopenia is difficult to predict because newborn platelet counts do not always correlate with maternal platelet
counts[2] or antiplatelet antibody titers.[8] It does correlate with the platelet count of previous first and second siblings at
birth.[22] Maternal platelet counts that fall within the reference range after previous splenectomy or corticosteroid treatment do not
guarantee a fetal platelet count within the reference range. In fact, splenectomy prior to pregnancy has been reported as a risk factor
for the development of newborn thrombocytopenia.[23] Splenectomy possibly increases the amount of free antiplatelet antibody in the
maternal sera due to the removal of the platelet/antibody destruction site.[24]
Fetal platelet counts can be obtained by fetal scalp sampling during labor or cordocentesis at 38-39 weeks' estimated gestational age;
however, neither is reliable at predicting thrombocytopenia at birth. Fetal scalp sampling is technically difficult and often
unreliable.[25] Owing to the risk of hemorrhage in the fetus and possible inaccuracy of the fetal platelet count, it is best avoided.[26] In a
clinical trial, platelet counts were obtained by cordocentesis in 42 women with ITP. Two of the 42 newborns had severe
thrombocytopenia at birth; neither was detected with cordocentesis.[27] At present, no reliable method of determining which newborns
are at risk for severe thrombocytopenia exists.
A platelet count at birth is recommended. Peripheral blood is preferred over heel sticks or cord samples because of better accuracy. A
cranial ultrasound should be considered if the platelet count is less than 50,000/L, even in the absence of symptoms. Intramuscular
injections such as vitamin K are best avoided.[15]
Some investigators have recommended performing a cesarean delivery in all women with ITP to minimize the trauma to the newborn
during the birth process. Cesarean delivery has not been demonstrated to prevent bleeding complications in thrombocytopenic
newborns. In a review of 474 newborns born to mothers with ITP, 29% of newborns born vaginally experienced a bleeding complication,
compared to 30% of newborns born via cesarean delivery.[28] Reviews published to date comparing vaginal birth to cesarean delivery in
women with ITP are retrospective studies; none are randomized controlled trials. However, in the absence of any clear benefit to the
neonate (given the low rate of intracranial hemorrhage in infants born to mothers with ITP), cesarean delivery should be reserved for
the usual obstetrical indications.
In women with a history of delivering a significantly thrombocytopenic newborn (platelet < 50,000/L) or a newborn with an intracranial
hemorrhage (platelet count < 100,000/L) in whom other illnesses commonly associated with thrombocytopenia have been
excluded,[29] test for NAIT. Perform maternal platelet antigen typing and confirm the presence of maternal antiplatelet antibodies with
specificity for paternal platelets. Perform antigen typing and zygosity testing on the father of the baby to determine if platelet antigen
incompatibility between the parents exists and if all potential offspring will be at risk for NAIT. If the father is a heterozygote, each
subsequent fetus has only a 50% chance of being affected. Fetal platelet typing can be performed on a chorionic villous sample,
amniocytes, or fetal blood to determine if the fetus carries the significant paternally derived antigen.
Prospective screening programs have demonstrated that NAIT usually develops in babies born to women with detectable antiplatelet
antibody.[9]Some investigators have suggested all pregnant women presenting for prenatal care be typed for platelet alloantigen to
determine if they are at risk for NAIT. Women at risk can be tested for the presence of platelet alloantibodies twice during gestation
(similar to current screening programs for Rh disease). A comparison of the effectiveness of this type of screening program estimated a
cost of $45,000 per case of alloimmunization diagnosed in whites.[9] The cost would be higher if testing were initiated in women of other
ethnic groups because the rate of NAIT is lower in nonwhite women. At present, universal prenatal screening is not recommended
because a clear clinical benefit has not been demonstrated.[10, 30]
Surgical Care
Splenectomy is an appropriate treatment for women with ITP with severe thrombocytopenia that is refractory to medical therapy.
Approximately two thirds of patients have a positive response, generally within a few days. Splenectomy is seldom performed during
pregnancy because most patients can be managed medically. If splenectomy is indicated, it should be performed in the second trimester.
Surgical interventions requiring general anesthesia are avoided in the first trimester if possible to prevent fetal medication exposures
during embryogenesis. Splenectomy is technically difficult in the third trimester because the enlarging uterus limits exposure to the
spleen. Successful splenectomy has been reported during cesarean delivery.[31]
Women with splenectomies should be immunized against pneumococcus, meningococcus, and Haemophilus influenzae.[10]