Page 2205 - Hematology_ Basic Principles and Practice ( PDFDrive )

1952 Part XII Hemostasis and Thrombosis

relatively straightforward. The majority of platelet alloantigens occur clinicians use IVIg for antenatal treatment. Corticosteroids (predni-
on GPIIIa, which is the most abundant platelet GP (50,000–75,000 sone or dexamethasone) given in combination with IVIg should be
copies per platelet). GPIIIa, also known as β3, forms a heterodimer considered for mothers at high risk, such as those with a previously
with platelet GPIIb to form the integrin α 2β 3 , which serves as the affected infant with intracranial hemorrhage or severe thrombocyto-
binding site for fibrinogen and enables platelet aggregation. penia or if the response to IVIg is suboptimal.
The most common platelet alloantigen implicated in NAIT is
HPA-1a. This important alloantigen is defined by a leucine (HPA-
1a) to proline (HPA-1b) substitution at amino acid 33 on GPIIIa. Fetal Monitoring During Pregnancy
Maternal incompatibility to HPA-1a is implicated in more than 80%
of women with NAIT. These women lack the common HPA-1a Serial ultrasonography is indicated for fetal surveillance. This provides
antigen (i.e., their genotype is HPA-1bb) and during pregnancy they a simple, noninvasive method for identifying fetal bleeds at an early
are immunized with fetal HPA-1a antigen inherited from the father. stage. FBS by percutaneous cannulation of the umbilical or intrahepatic
The next most commonly implicated antigens in NAIT are HPA- vein may be a way of capturing high-risk fetuses, identifying those who
5a5b on GPIa/IIa and HPA-15a15b on the glycosylphosphatidylinosi- require treatment, and monitoring response to therapy. However, FBS
tol–anchored protein, CD109. Only 6 of the 28 platelet antigen systems is technically challenging and is associated with significant morbidity
have been defined by maternal alloantibodies against both alleles; these and mortality. In one study, 6% of FBS procedures were associated
include the HPA 1, 2, 3, 4, 5, and 15 systems. There are a number of with complications, including fetal death from exsanguination and
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other low-frequency alleles, the majority of which are expressed on premature induction of labor. Furthermore, a platelet transfusion
platelet GPIIb/IIIa and are usually found within a single family. protocol based on the detection of fetal thrombocytopenia would
Although maternal immunization to low-frequency antigens is impli- necessitate frequent FBS procedures because of the short (7-day) life
cated in some cases of NAIT, these antigens account for a minority of span of transfused platelets. Because the risks associated with FBS
the NAIT cases that remain unresolved after investigation for common exceed the benefits, routine FBS is not recommended.
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HPA antigens. Frequently, discrepancies in human leukocyte antigen
(HLA) and ABO, which are also expressed on platelets, are found during
the course of investigations for NAIT; however, their significance is Mode of Delivery
uncertain. A database of genetically confirmed alloantigens is maintained
by the European Bioinformatics Institute (http://www.ebi.ac.uk). There is no evidence that planned cesarean section is safer than uncom-
plicated vaginal delivery for infants with NAIT. Nonetheless, planned
Management cesarean section delivery can ensure that personnel and resources,
including antigen-compatible platelet transfusions, are readily available.
Management of Infants After Delivery
Population Screening for Neonatal Alloimmune
When NAIT is suspected and depending on the platelet count, Thrombocytopenia
treatment should be initiated even before confirmatory test results are
available. It is important to appreciate that moderate or severe Universal NAIT screening programs for all pregnant women are not
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thrombocytopenia at birth (20–50 × 10 /L) can worsen over the next currently available because of the difficulty in early identification of
few days. Treatment should be initiated immediately if thrombocy- at-risk women and the lack of specific and proven treatments. Screen-
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topenia is severe (platelets <50 × 10 /L); if there are petechiae or ing algorithms also have to account for the large difference in numbers
purpura; or if there is evidence of serious bleeding, such as intra- of women lacking an antigen and those who will later develop NAIT.
cranial bleeding on cranial ultrasonography. The initial treatment is About 2% of women will be identified as HPA-1bb, whereas only 1
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platelet transfusion along with high-dose IVIg (1–2 g/kg). Ideally, in 20 of these will have an affected child because of HPA-1a immu-
platelet products for transfusions should be alloantigen compatible; nization. One study screened 100,448 pregnant women and offered
however, if these are unavailable, random donor platelets can be used those with HPA-1a antibodies early cesarean section together with
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because they often produce adequate increases in the platelet count. 22 compatible platelet transfusions. This approach identified 161
affected infants, of whom three (6%) died or had an intracranial
bleed, compared with 10 of 51 infants (20%) born to mothers who
Antenatal Management of the Mother were not screened. These results are encouraging, and additional
studies of NAIT screening programs are ongoing.
Women with a previously affected infant with NAIT are at high risk
of having another affected infant. Consequently, careful management
in subsequent pregnancies is required. Similar to HDN, the disorder POSTTRANSFUSION PURPURA
is often more severe in subsequent pregnancies than it is in the first.
The exception is if the father is heterozygous for the implicated PTP is a rare thrombocytopenic syndrome that is provoked by an
platelet antigen, in which case antigenic testing can be performed by immune-mediated reaction against HPAs, most frequently HPA-1a.
amniocentesis to determine if the fetus is at risk and whether treat- PTP presents 5–10 days following exposure to platelets or platelet
ment is required. antigenic material in blood transfusions with profound thrombocy-
Antenatal treatment options for at-risk mothers during subsequent topenia and clinically significant bleeding.
pregnancies range from careful observation, to IVIg with or without
corticosteroids, to fetal blood sampling (FBS) and intrauterine
platelet transfusion. Invasive strategies that include FBS are associated Epidemiology
with a high rate of complications, including fetal death and premature
labor; thus a noninvasive approach is often recommended. PTP is rare with an estimated incidence of 1–2 per 100,000 transfu-
The mainstay of antenatal therapy for women with a previously sions. Data from the Serious Hazards of Transfusion surveillance
affected infant is high-dose IVIg (1–2 g/kg) administered weekly program from the United Kingdom have shown that the incidence
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throughout pregnancy starting at 18–22 weeks of gestation. A sys- of PTP has decreased in the last decade (Fig. 131.4). Reasons for
tematic review summarizing the results of four randomized trials that this trend may be related to universal leukoreduction, which was
included 206 women compared weekly IVIg with a variety of other implemented in the United Kingdom in 1999. The average annual
therapies, including alternate dosing of IVIg or IVIg plus corticoster- incidences of PTP in the years preceding 1996–99 and following the
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oids. Although no definitive conclusions could be drawn, most implementation of universal leukoreduction between 2000 and 2005