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2012 Part XII: Hemostasis and Thrombosis Chapter 117: Thrombocytopenia 2013

allele in HPA-1a–negative women increases the NAIT risk as much as available tests usually require invasive procedures such as amniocentesis
140-fold. 361 or fetal blood sampling. Cell-free fetal DNA obtained from maternal
NAIT tends to be clinically more severe in cases with alloantibod- blood has been studied for fetal platelet genotyping. However, these
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A
ies against HPA-1a. HPA-1 (Pl ) antigens are expressed on platelet tests need validation. The treatment options in high-risk NAIT are
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integrin β . Anti–HPA-1a antibodies possibly impair platelet aggrega- weekly IVIG administration to the mother, with or without glucocorti-
3
tion, which may explain the severity of bleeding symptoms. 362 coids, serial in utero platelet transfusions, in utero IVIG administration,
and early delivery (after 32 weeks of gestation). Maternal IVIG adminis-
CLINICAL FEATURES tration at a dose of 1 g/kg per week with or without glucocorticoids may
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IgG alloantibodies can cross the placenta as early as week 14 of preg- increase fetal platelet counts, although not all studies support this
355,362
nancy, and placental passage increases with gestational age. These conclusion. IVIG can be administered directly to severely throm-
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antibodies bind to fetal platelets and lead to their destruction. In severe bocytopenic fetuses, although this also may fail to raise fetal platelet
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cases, intracranial hemorrhage and hydrocephalus may develop and counts. In patients who do not respond to IVIG and glucocorticoid
cause fetal death or severe neurologic sequelae. The diagnosis can be administration, serial transfusion of matched platelets should be con-
difficult in the first affected fetus in a family. Ultrasonography is usually sidered. Matched platelet transfusions will only transiently increase the
not helpful unless it detects bleeding or hydrocephalus. Unexplained fetal platelet count because the transfused platelets also are targeted by
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fetal deaths in the maternal history or fetal hydrocephalus or bleeding in the offending antibodies. Serial platelet transfusions may increase
previous pregnancies may alert the physician to the possibility of NAIT. the cumulative risk of hemorrhage and procedure-related hemorrhage
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Usually the diagnosis of NAIT is possible after birth. NAIT should be and fetal loss. In severely thrombocytopenic fetuses, early delivery
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suspected in a thrombocytopenic neonate with extensive purpura or by cesarean section may reduce the risk of intracranial hemorrhage.
visceral hemorrhage but no evidence of sepsis, skeletal anomalies, or New therapeutic strategies are under investigation, including vac-
other systemic diseases that may cause thrombocytopenia, including cines and competitive molecules that competitively bind anti–HPA-1a
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maternal ITP. Affected babies may have no signs or symptoms (13 to 59 antibodies.
percent of cases), or they may have signs of bleeding (18 to 65 percent of
cases) or intracranial hemorrhage (22 to 23 percent of cases). In a case ABNORMAL PLATELET DISTRIBUTION
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series of 88 infants with NAIT resulting from anti–HPA-1a antibodies,
90 percent had purpura, 66 percent had hematomas, 30 percent had OR POOLING
gastrointestinal bleeding, and 14 percent had intracerebral hemorrhage. SPLENOMEGALY AND HYPERSPLENISM
Bleeding may be delayed, as the platelet count usually falls further dur-
ing the first several days of life. Death or neurologic impairment occurs Splenomegaly may lead to thrombocytopenia by inducing a revers-
in up to 25 percent of infants. Platelet counts recover to normal in 1 to ible pooling of up to 90 percent of total body platelets. 370,371 This pro-
2 weeks. 364 cess can be thought of as an exaggeration of normal splenic pooling, in
The diagnosis of NAIT usually can be confirmed by tests for cir- which approximately one-third of the platelet mass is contained within
culating maternal alloantibodies against fetal antigens (usually by the spleen at any one time (Chap. 55). The survival of platelets within the
MAIPA) or modified antigen capture enzyme-linked ımmunosorbent spleen can be normal or moderately reduced. Thus, the total blood
assay (MACE) or by platelet typing of the parents and neonate by either platelet pool in a patient with splenomegaly could be normal even when
genotyping or ELISA. These tests may fail to yield the diagnosis because the counts measured in venous blood are only 20 percent of normal.
private HPA antigens may be responsible for NAIT. 317,322,357 Platelet production is usually normal in patients with splenomegaly, as
estimated by dividing the total body platelet mass by the platelet life
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MANAGEMENT span. This finding provides further evidence that platelet production
is more closely tied to total platelet mass than to circulating platelet
Postnatal count.
In the clinical setting, the confirmation of a diagnosis of NAIT by plate- The most common disorder causing thrombocytopenia because of
let genotyping, MAIPA, or MACE will require days; thus, an infant born splenic pooling is chronic liver disease with portal hypertension and
with severe thrombocytopenia with no obvious cause such as sepsis congestive splenomegaly. In patients with cirrhosis and portal hyper-
should be regarded as having NAIT. The alternatives in the management tension, moderate thrombocytopenia is the rule. However, in such cases
of affected neonates are IVIG, glucocorticoids (alone or combined with the thrombocytopenia often results from both splenic pooling and
IVIG), and platelet transfusions. IVIG and/or glucocorticoid therapy reduced hepatic production of TPO.
may increase platelet counts rapidly, although a substantial increase of Thrombocytopenia associated with splenomegaly is often of no
platelet counts usually occurs after 24 to 72 hours. In cases with severe clinical importance and generally does not require therapy. Signs and
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bleeding, platelets should be transfused. Transfused platelets should be symptoms are related to the primary disorder, and bleeding manifes-
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ABO and (Rh)D compatible and HPA-1a–negative if possible. If such tations result primarily from coagulation abnormalities caused by the
platelet suspensions are not available, transfusion of washed and irra- underlying liver disease. This finding is consistent with the relatively
diated maternal platelets to the affected fetus is another alternative. moderate degree of thrombocytopenia, the near-normal total body con-
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317
Repeated platelet transfusions may be required. All affected infants tent of platelets, and the ability to mobilize platelets from the spleen to
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should be screened with ultrasound for intracranial hemorrhage. 366 replenish losses. When splenectomy is performed for another reason,
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however, the platelet count predictably returns to normal or thrombo-
Prenatal cytosis may even occur. Platelet counts may also return to normal in
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Pregnant women who had a previous thrombocytopenic infant attribut- patients following surgical correction of portal hypertension by porto-
able to NAIT should be carefully monitored in a center with experience systemic shunting. Platelet transfusions usually are not needed for
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with NAIT, because thrombocytopenia will be more severe in a second splenomegaly-associated thrombocytopenia and rarely produce signifi-
affected child. Current therapeutic alternatives for antenatal manage- cant increases in the platelet count because as much as 90 percent of the
ment of NAIT are unsatisfactory. Fetal platelet typing is important, but transfused platelets will be sequestered in the spleen.

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