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2010 Part XII: Hemostasis and Thrombosis Chapter 117: Thrombocytopenia 2011

which can be modified as appropriate. 147,318 Fetal side effects will be min- although it is quite rare even in ITP patients with platelet counts lower
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imal with a low-dose glucocorticoid regimen, because approximately than 20 × 10 /L.
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90 percent of the glucocorticoid dose is metabolized in the placenta. Severe neonatal thrombocytopenia (platelet counts <20 × 10 /L)
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IVIG is indicated in pregnant patients who do not respond to or tolerate occurs in 3 to 5 percent of ITP pregnancies and moderate neonatal
330
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glucocorticoid treatment, or when it is necessary to rapidly increase the thrombocytopenia (platelet counts <50 × 10 /L) in 9 percent. Severe
platelet count. A dose of 1 g/kg per day for 2 days, or 400 mg/kg per day bleeding occurs in less than 1 percent of the babies. If the newborn is
for 5 days can be used alone, or combined with low-dose prednisone. If thrombocytopenic, the platelet count should be measured daily for
the initial therapy with glucocorticoids and IVIG fails, all second-line 1 week. IVIG is preferred in neonates with severe thrombocytope-
therapies generate some concern. Anti-(Rh)D can cause severe hemo- nia. Platelet transfusions and glucocorticoids are added if bleeding is
lytic reactions in both the mother and the fetus, and should be used life-threatening.
only in patients refractory to glucocorticoids and IVIG. 148,318 Experience If thrombocytopenia associated with SLE and APS has been com-
with azathioprine and cyclosporine in pregnancy is largely based on the plicated with prior pregnancy loss and thromboembolism, pregnant
case series from patients with rheumatologic disorders and solid-organ patients should receive antithrombotic prophylaxis with low molecular
transplantation. These studies reported that exposure to these drugs heparin and/or aspirin if possible. Although there is no defined thresh-
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during pregnancy was not associated with an increase in the risk of neg- old platelet level for these patients, platelet counts over 50 × 10 /L are
ative pregnancy outcomes and had no significant toxicity to the fetus. considered safe for both anticoagulant and antiplatelet therapy. 318
326
Splenectomy can be used in pregnant ITP patients who are unrespon-
sive or intolerant to available drugs and at significant risk of bleeding. If MICROANGIOPATHIC DISORDERS IN
splenectomy is necessary, it is preferable that it be performed during the
second trimester. 147,191 PREGNANCY: PREECLAMPSIA–ECLAMPSIA,
Rituximab is not an optimal drug for use during pregnancy. It can HELLP, THROMBOTIC THROMBOCYTOPENIC
cross the placenta, and transfer from mother to fetus increases with ges- PURPURA-HEMOLYTIC UREMIC SYNDROME,
tational age. The half-life of the drug is also very long; rituximab can be
found in blood 6 months after of an infusion. In a review evaluating 231 AND ACUTE FATTY LIVER OF PREGNANCY
pregnancies with rituximab exposure reported in the literature, most of Preeclampsia
the patients had SLE, rheumatoid arthritis. and B-cell lymphoma, with This condition is a systemic disorder characterized by new onset hyper-
rituximab being used in combination with other drugs. This retrospec- tension after 20 weeks of gestation, and primarily occurs near term.
tive study showed low risk of premature births, hematologic abnormali- Although proteinuria occurs in the majority of these cases, the Amer-
ties and birth defects. However, because of the lack of controlled studies, ican College of Obstetricians and Gynecologists (ACOG) 2012 classi-
it is recommended that women avoid pregnancy for 1 year after rituxi- fication accepts the presence of one of the following in the absence of
mab infusion. 327 proteinuria: thrombocytopenia (less than 100 × 10 /L), abnormal liver
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TPO receptor agonists were found to cause fetal loss and reduced function tests, renal insufficiency, pulmonary edema, or cerebral and
328
fetal body weight in animal studies, and there is no data on humans. visual symptoms. Eclampsia is defined by the occurrence of epileptic
Vinca alkaloids, cyclophosphamide, and danazol are not recommended seizures in a preeclamptic woman during the peripartum period. 335–337
during pregnancy. Preeclampsia complicates 5 to 8 percent of all pregnancies, and is
The optimal mode of delivery in pregnant ITP patients has not a major contributor to maternal and fetal morbidity and mortality
been determined. Because earlier studies reported that thrombocy- (Chap. 7). 335,338 Thrombocytopenia is seen in approximately 50 percent
topenic neonates have an increased risk for intracranial hemorrhage, of women with preeclampsia, with the severity of thrombocytopenia
some physicians recommend delivering the baby by cesarean section in correlating with the severity of the preeclampsia. 339
women with ITP to avoid injuries to the fetus during passage through Attempts to define the pathogenesis of preeclampsia have engen-
the birth canal. However, because of the rarity of intracerebral hem- dered numerous theories. One clear aspect of the pathogenesis is
329
340
orrhage, there are no data proving the effectiveness of cesarean delivery the requirement for a placenta, given that the condition can be pro-
in reducing the occurrence of intracerebral hemorrhage in the throm- duced in abdominal pregnancies and molar pregnancies. The dis-
341
bocytopenic fetus. Measurement of platelet counts in infants before ease appears to be initiated by defective invasion of the uterine spiral
322
delivery, such as by percutaneous umbilical cord blood sampling or fetal arteries by placental cytotrophoblasts. During normal implantation,
scalp vein sampling after cervical dilatation, is not recommended rou- these cells convert from epithelial to endothelial morphology, a process
tinely because the risk of bleeding during these procedures is high. 330–332 called pseudovasculogenesis. 342,343 In preeclampsia, this process is defec-
The mother’s platelet count at delivery does not correlate with the tive, resulting in diminished maternal blood flow to the placenta and
infant’s platelet count. In ITP patients who gave birth more than once, placental hypoxia. Through unknown mechanisms, the production of
however, the first infant’s platelet count at birth may be a predictor of membrane and soluble forms of the vascular endothelial growth factor
severe thrombocytopenia in subsequent pregnancies and may justify (VEGF) receptor fms-like tyrosine kinase-1 (Flt1) is increased, with
344
further obstetric management. 322,331,333 On the other hand, discordances resultant increases of soluble Flt1 (sFlt1) in the amniotic fluid and
345
in degree of thrombocytopenia between dichorionic twins in ITP indi- maternal circulation. sFlt1 is the product of an alternately spliced
346
cate that fetal factors also are important. In conclusion, there is as form of the Flt1 messenger RNA that lacks the transmembrane and
334
yet no definitive method to predict fetal platelet count in pregnant ITP cytoplasmic domains present in the full-length receptor. A large vol-
patients, and the method of delivery should be determined by obstetri- ume of evidence implicates sFlt1 as playing a key role in the patho-
cal evaluation. During vaginal delivery, the target maternal platelet genesis of preeclampsia. By binding to VEGF and the related placental
count should be 50 × 10 /L or higher. If cesarean section or epidural growth factor, sFlt1 blocks their favorable effects on vascular endothe-
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anesthesia is required, the platelet count should be maintained over 70 lium. Its expression in rats produces a syndrome akin to preeclampsia:
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to 80 × 10 /L. 147,148,318 Glucocorticoids, IVIG and platelet transfusions hypertension and proteinuria associated with glomerular endothelio-
may help to keep platelet counts in a safe range in these patients. Blood sis (occlusion of glomerular capillaries by swollen endothelial cells).
products should be available for possible severe bleeding during labor, Endoglin is another angiogenic receptor expressed on endothelial cells

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