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2206 Part XIII Consultative Hematology

TABLE Initiation of Treatment in Pregnant Patients With Thrombocytopenia is observed in 15% to 50% of patients with this
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151.1 Idiopathic Thrombocytopenic Purpura condition. Clinical manifestations include a maternal syndrome
characterized by hypertension, proteinuria, and systemic abnormali-
Platelet Count Treatment ties as well as a fetal syndrome characterized by fetal growth restric-
<10,000/µL Platelet transfusion for life-threatening bleeding tion, preterm delivery, and hypoxia-induced neurologic damage. 72,74
In most instances, preeclampsia occurs during a woman’s first
10,000-30,000/µL Consider monitoring in first trimester; treat in pregnancy, but it can recur in a subsequent pregnancy or occur for
second or third trimester
the first time in a woman with one or more previously unaffected
>30,000/µL Clinically monitor pregnancies. Risk factors for the disorder include, but are not limited
to, preeclampsia in a previous pregnancy, a family history of pre-
eclampsia, chronic hypertension, obesity, multifetal gestation, rheu-
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matic disease, and preexisting thrombophilia. With respect to
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be normal. Bone marrow biopsy and aspirate are not indicated unless thrombophilia, a case–control study by Mello and colleagues sug-
there are other hematologic abnormalities present. gests that the prevalence of an underlying thrombophilia is signifi-
Treatment options are generally similar to those for nonpregnant cantly higher among women who develop preeclampsia during
patients with ITP (Table 151.1). Platelet transfusions are reserved for pregnancy than among those who have uneventful pregnancies.
life-threatening bleeding because the lives of transfused platelets are HELLP syndrome represents a severe variant of preeclampsia. In
usually short in ITP. Glucocorticoids are considered first-line treat- the majority of cases, patients who develop the syndrome are white
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ment; prednisone is usually initiated at 1 mg/kg based on the patient’s and multiparious. The median age of affected patients is 25 years.
baseline weight. Side effects of prednisone should be discussed with The time of presentation during pregnancy ranges from the midtri-
the patient and include weight gain, bone loss, hypertension, and mester (15%) to term (18%). In 30% of patients who develop
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gestational diabetes. IVIg can also be used. It is a means of rapid HELLP, it develops within 2 days after delivery. Patients typically
increase in platelet count. It is particularly used to help increase exhibit vague symptoms such as malaise, fatigue, epigastric or right
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platelet counts a few days before delivery. It is usually administered upper quadrant pain, nausea, vomiting, and flulike symptoms.
at a dose of 2 g/kg over 2 days. However, the improvement in platelet Because of the nonspecific nature of these symptoms, diagnosis is
count is fairly transient. Splenectomy is also an option indicated for often delayed; one study found an average time to diagnosis of 8 days
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refractory thrombocytopenia; it is best performed during the second in women with HELLP syndrome. Clinical findings at the time of
trimester. diagnosis (weight gain or edema, hypertension, and proteinuria) are
Other agents such as danazol, cyclophosphamide, and vinca similar to those observed in preeclampsia. 77
alkaloids, although used in the management of ITP in nonpregnant Although various criteria have been used in diagnosing HELLP
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individuals, are teratogenic and should be avoided during pregnancy. syndrome, they generally share the following features: signs of micro-
Use of cyclophosphamide has been associated with birth defects. angiopathic hemolytic anemia, serum lactate dehydrogenase greater
Danazol may cause clitoral enlargement and labial fusion in female than 600 U/L or serum total bilirubin greater than 1.2 mg/dL,
fetuses when given in the first trimester. 63,64 The use of rituximab has aspartate aminotransferase greater than 70 IU/L, and a platelet count
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never been studied systematically in this setting and is considered a lower than 100,000/µL. Martin and colleagues further defined
pregnancy class C drug. Although case reports of its use exist, it is HELLP syndrome on the basis of platelet count. According to this
not generally recommended in this case. Animal data indicate that classification, patients with class 1 HELLP syndrome have a platelet
thrombopoietin mimetics may cause fetal harm, and little is known count lower than 50,000/µL, those with class 2 disease have a platelet
about their use in pregnant patients. A registry has been developed count between 50,000 and 100,000/µL, and individuals with class 3
for pregnant patients treated with thrombopoietin mimetics. HELLP syndrome have a platelet count higher than 100,000/µL. As
As discussed previously, maternal antiplatelet IgG can cross the might be expected, women with class 1 HELLP syndrome required
placenta and cause thrombocytopenia in fetuses. Percutaneous a recovery period in the aftermath of their illness.
umbilical blood sampling is the most accurate means to obtain the Although the precise mechanism through which preeclampsia
fetal platelet count. However, the procedure is associated with a high develops is uncertain, research in the field continues to advance
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complication rate and 1% fetal mortality. Intrapartum fetal scalp understanding of the underlying pathophysiology. Endothelial cell
sampling represents an alternative, but the accuracy of this technique dysfunction after placentation appears to play a central role in the
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is only 50% to 70%. The maternal platelet count and antiplatelet pathogenesis of the disease. During development of the placenta,
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antibody level do not accurately predict the fetal platelet count. placental trophoblast cells interface with the epithelial layer of the
Overall, 10% of babies born to mothers with ITP have a platelet uterus, forming the decidua. Penetration and remodeling of maternal
count less than 50,000/µL, but less than 5% have a platelet count spiral arteries beginning at week 9 during pregnancy increase placental
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less than 20,000/µL. Treatment of pregnant women with IVIg or perfusion and improve oxygenation for the developing fetus under
steroids does not appear to affect the platelet count of fetuses. 68,69 normal conditions. 80
Thrombocytopenia places neonates at risk for bleeding events, Cellular abnormalities such as those described impair placental
including intracranial hemorrhage, although this complication is implantation and vasculogenesis, leading to fetal hypoxia and the
rare. 70 release of vasoactive compounds such as endothelin, nitric oxide, and
In terms of delivery, at present, available guidelines on the subject prostaglandins. High levels of endothelin, a potent vasoconstrictor,
suggest that obstetric factors, rather than hematologic ones, should are seen in preeclamptic patients, and injection of endothelin into
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guide the manner of delivery. After the delivery of a child, the cord rabbits produces a syndrome similar to HELLP syndrome. 81,82 The
blood platelet count is checked and the newborn platelet count fol- activity of endothelin, nitric oxide, and prostaglandins leads to
lowed because thrombocytopenia is often most severe 4 to 6 days hypertension and platelet activation. Angiogenic factors such as
after delivery and resolves as maternal antiplatelet IgG is cleared. vascular endothelial growth factor 1 (VEGF 1) are elevated in pre-
eclampsia compared with normal pregnancy. Injury to the vascular
endothelium results in fibrin deposition, further platelet activation,
Preeclampsia and HELLP Syndrome and the release of additional vasoactive agents such as serotonin and
thromboxane A 2. The etiology of thrombocytopenia in preeclampsia
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Thrombocytopenia in pregnant woman also occurs in association is likely related to increased antiplatelet IgG levels or to activation
with preeclampsia and HELLP syndrome (hemolysis, elevated liver of the coagulation cascade with subsequent consumption of
enzymes, low platelet count), potentially severe multisystem disor- platelets. 84,85
ders associated with pregnancy. In previously healthy nulliparous These events lead to the multisystem dysfunction seen in patients
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women, the incidence of preeclampsia is between 2% and 7%. with HELLP syndrome. Fibrin deposition in the hepatic sinusoids