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124 Part III: Epochal Hematology Chapter 8: Hematology during Pregnancy 125

reviewed 155 pregnancies in 86 women with ET, and only 59 percent of of major thrombosis, or of major bleeding, platelet count greater than
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these pregnancies resulted in a live neonate. First-trimester abortion 1000 × 10 /L, familial thrombophilia or cardiovascular risk factors) were
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was seen in 31 percent of pregnancies, the main cause being placental recommended to receive interferon. The Italian panel also recommended
infarction. Maternal thrombotic or hemorrhagic complications were avoidance of anagrelide in pregnancy because of uncertainty about its
infrequent, but were more common than in normal pregnancy. Preg- teratogenic potential; however, several normal infants have been born to
nancy did not appear to adversely affect the course and prognosis of ET. women who inadvertently took this drug during pregnancy (FDA docu-
A meta-analysis revealed a benefit for aspirin treatment, whereas ments submitted by the manufacturer). Although the risk of congenital
the benefit of heparin prophylaxis has not been established, but may anomalies among infants of women treated with hydroxyurea during
have a role in selected cases. If cytoreductive therapy becomes nec- pregnancy was thought to be substantial, of 15 infants born to women
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essary, interferon-α is the drug of choice. A similar incidence of preg- treated with hydroxyurea at conception and/or during pregnancy, no
nancy complications in patients with ET was reported in a series from malformations were observed, and only one stillbirth was reported in a
the Mayo clinic. Another large single institution study of 68 young ET woman who also had eclampsia. At least one publication has identified
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patients demonstrated that for both polycythemia vera (PV) and ET, the presence of the JAK2 V617F mutation as a risk factor for pregnancy
most thromboses in young patients occurred at the time of diagnosis complications; however, to date there is no consensus on whether to
and also suggested, but did not prove, the benefit of aspirin. The most manage these patients differently. A review of 158 young women with
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detailed analysis was published by the Italian Society of Hematology ET experiencing 237 pregnancies demonstrated that pregnancy compli-
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in its guidelines. The Society’s report analyzed pooled outcome data cations are associated with higher risk of subsequent thrombosis. 142
from 461 pregnancies in women with ET. The mean age of the pregnant
patients was 29 years, and the mean platelet count at the beginning of POLYCYTHEMIA VERA
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pregnancy was 1000 × 10 /L, which declined to 400 × 10 /L in the sec-
9
ond trimester. This decrease in the platelet count during pregnancy doc- Although there is significant overlap in the clinical features of PV and
umented for the first time the anecdotal observation that some women ET, there are some noteworthy differences (Chap. 84). In PV, the num-
with ET spontaneously normalize their platelet count during their preg- ber of reported pregnancies is low because most PV patients are past
nancy. (The authors of this chapter have rarely observed this phenome- childbearing age, and comorbid conditions are more frequent. One
non; however, in one of their ET patients a spontaneous, but transient, authoritative review suggests maintaining the hematocrit below 45
ET remission occurred in the first pregnancy, but not in the following percent in pregnancy, and another recommends using interferon-α
141
pregnancy.) The Italian study found that 44 percent of pregnancies when myelosuppression is indicated. Another noted authority in PV
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were unsuccessful in women with ET, a figure that is threefold higher recommends that the hematocrit be kept lower than 35 percent in preg-
than in the general population. Among the 461 pregnancies there were nancy. However, because of a dearth of data and controlled studies,
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13 pre- or postpartum significant bleeding events. The median duration optimal management of PV pregnancies is poorly defined and agreed
of gestation was 38 weeks because of abortions and preterm deliveries. upon protocols are not available. None of the available information
Cesarean section was necessary in 15 percent of the patients. The plate- allows definite therapeutic recommendations; however, some authori-
let count at the beginning of pregnancy did not predict pregnancy out- ties recommend that, at a minimum, all pregnant patients with PV be
come. Placental infarctions were reported in 18 pregnancies and these treated with low-dose aspirin. 144
were associated with intrauterine fetal growth retardation (11 pregnan-
cies). Placental abruption was reported in 3.6 percent of ET pregnancies
compared to 1 percent in the non-ET population. Preeclampsia was HEMOGLOBINOPATHIES
seen at a rate equal to that seen in non-ET pregnancies. Postpartum
thrombotic episodes were reported in 5.2 percent of the pregnancies SICKLE SYNDROMES
and included venous thrombosis, pulmonary embolism, sagittal sinus Although pregnancy in patients with sickle cell trait is typically
thrombosis, transient ischemic attacks, and Budd-Chiari syndrome uneventful, these patients probably have an increased risk for urinary
(rates for all problems were significantly higher than in non-ET preg- tract infection. Earlier studies suggested an increased risk for preec-
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nancies). The impact of therapy was difficult to evaluate because man- lampsia in patients with sickle cell trait, but a large study demonstrated
agement of ET pregnancies was heterogeneous; no specific therapy for that sickle cell trait is not an independent risk factor for preeclampsia
ET was given in 48 percent of the pregnancies. Aspirin therapy at doses (Chap. 49). 146
ranging from 75 to 500 mg per day was used in 106 pregnancies, low- Patients with sickle cell anemia should receive at least 1 mg of
molecular-weight heparin (pre-/postpartum) was used in 26 pregnan- folate per day; however, they should not receive iron supplementation
cies, interferon-α was used in 19 pregnancies, and a handful of patients until a ferritin level is checked and iron deficiency is documented.
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had various chemotherapies and radioactive phosphorus. When the Because of the risk of fetal malformation, hydroxyurea should be dis-
outcome of the ET pregnancies was reviewed, 74 percent of patients continued at least 3 months before pregnancy. However, successful
treated with aspirin during pregnancy had successful pregnancies, outcomes have been reported in sickle cell disease patients who were
whereas 55 percent of the patients not receiving aspirin had successful exposed to the drug while pregnant. Women with sickle cell ane-
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pregnancies. Based on the detailed analyses of all variables, this panel of mia and their fetuses have an increased risk of complications during
experts felt that there was no direct evidence of the efficacy of aspirin in pregnancy. A large study of more than 17,000 deliveries to women with
pregnant ET women, but that “it seems possible that aspirin increases sickle cell anemia compared with controls demonstrated that infectious
the rate of successful pregnancies.” The panel also recommended that complications, including pneumonia, systemic inflammatory response
ET patients with a thrombotic episode (peripheral or placental) during syndrome, and sepsis, were more common in the women with sickle
pregnancy should receive low-molecular-weight heparin at therapeutic cell anemia. Furthermore, thrombotic complications such as cerebral
doses and oral anticoagulant therapy (PT international normalized ratio vein and deep vein thrombosis and pregnancy complications includ-
2 to 3) for at least 6 weeks postpartum. Longer periods of anticoagula- ing preeclampsia, eclampsia, abruption and antepartum bleeding were
tion were recommended for patients with familial thrombophilia. Preg- significantly more common in patients with sickle cell anemia. As in
nant women deemed candidates for platelet-lowering therapy (a history previous reports, rates of intrauterine growth retardation and preterm

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