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122 Part III: Epochal Hematology Chapter 8: Hematology during Pregnancy 123

suggest that gestational thrombocytopenia occurs in the second and the differentiation from thrombotic thrombocytopenic purpura (TTP)/
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third trimesters, with platelet counts rarely falling below 70,000/μL. hemolytic uremic syndrome becomes more difficult. Some data suggest
Gestational thrombocytopenia can sometimes be diagnosed with cer- that maternal recovery from the HELLP syndrome is accelerated by
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tainty only after delivery; usually there is no past history of low platelets, administration of intravenous dexamethasone ; however, a meta-anal-
except perhaps with previous pregnancies, the platelet count returns to ysis demonstrated no clear advantage to the use of glucocorticoids to
normal after delivery, and there is no association with fetal thrombocy- decrease maternal or perinatal morbidity or mortality. A collabora-
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topenia. It is not clear whether or not gestational thrombocytopenia is a tive randomized controlled trial of glucocorticoids in HELLP syndrome
variant of immune-mediated platelet destruction (Chap. 117). 58 (COHELLP) is underway to determine the effectiveness of dexametha-
In contrast to gestational thrombocytopenia, ITP can occur at any sone to accelerate the postpartum recovery of patients with class I
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point in pregnancy and the fall in platelet count can be severe. Diagnosis HELLP syndrome. Observation or treatment of HELLP with glucocor-
is essentially the same as it would be in any patient in that alternative ticoids alone postpartum should probably not persist beyond the third
causes of thrombocytopenia must be ruled out. As in other cases, treat- postpartum day. If the patient is not clearly improving, plasma exchange
ment of ITP in pregnancy must take into account the severity of the should be initiated as one would do for thrombotic thrombocytopenic
thrombocytopenia and the presence or absence of symptoms. In gen- purpura (TTP). 69,70 Although not associated with hypertension, acute
eral, platelet counts less than 10,000/μL require treatment regardless of fatty liver of pregnancy is another rare disorder that can present in the
the trimester; platelet counts of 30,000 to 50,000/μL without bleeding third trimester with severe liver dysfunction, but thrombocytopenia, if
require no treatment, and platelet counts of 10,000 to 30,000/μL in later present, is generally mild and does not require treatment (Chaps. 51,
trimesters or in the presence of bleeding require treatment. Although 117, and 129).
glucocorticoid and intravenous immunoglobulin are safe in preg-
nancy, they may have no effect on fetal counts and should only be used
to treat the mother. Splenectomy for ITP in pregnancy is best done THROMBOPHILIA
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in the second trimester if platelet counts are extremely low and unre-
sponsive to treatment. One small study evaluated the safety of anti-D FETAL LOSS AND COMPLICATIONS
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antibodies during pregnancy; all 10 of the women studied achieved Pregnancy is a prothrombotic state. Inherited prothrombotic conditions
a platelet count greater than 30,000/μL, but larger studies are needed contribute to 50 percent of the cases of venous thromboembolism and
before this intervention can be recommended. Similarly, there are case pulmonary embolism, as well as to stroke in pregnancy and the puer-
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reports of rituximab administration for treatment of refractory ITP perium. Hereditary thrombophilias (Chap. 130) may also predispose
in pregnancy; at least one report demonstrated transient inhibition of to fetal loss through placental vascular disorders. The best evidence for
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neonatal B-lymphocyte development. There are no adequate and well- an association between a thrombophilia, albeit acquired, and recurrent
controlled studies of either eltrombopag or romiplostim in pregnant fetal loss exists for antiphospholipid antibody syndrome in which the
women and both are considered pregnancy category C drugs. In ani- association between the antibodies and pregnancy loss has been recog-
mal studies, both drugs crossed the placental and fetal effects included nized for more than 20 years. As many as 20 percent of women with
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thrombocytosis, postimplantation loss, increase in fetal mortality, recurrent fetal loss have antiphospholipid antibodies, and studies show
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but no major structural malformations were reported. Case reports that without treatment up to 90 percent will experience fetal loss. One
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describing the use of romiplostim in pregnancy have appeared and in study suggests that poor pregnancy outcomes occur more frequently
one report the newborn had severe thrombocytopenia at birth compli- in primary antiphospholipid syndrome when patients have more than
cated by intracranial hemorrhage. Maternal platelet counts of greater one positive laboratory test (lupus anticoagulant, immunoglobulin [Ig]
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than 50,000/μL usually are safe for both vaginal and cesarean delivery. G/IgM anticardiolipin, IgG/IgM antihuman β -glycoprotein I antibod-
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In most cases, spinal anesthesia should not be used if the platelet count ies). In a randomized controlled trial including 90 women with a his-
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is less than 75,000/μL. Less than 5 percent of babies born to mothers tory of recurrent miscarriage associated with phospholipid antibodies
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with ITP have platelet counts less than 20,000/μL, although there does (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin
seem to be some correlation between very severely depressed maternal antibodies (or anticardiolipin antibodies), the rate of live births with
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platelet count and severe thrombocytopenia in the newborn. No clear low-dose aspirin (75 mg/day) and unfractionated heparin (5000 U sub-
recommendations can be given for measuring fetal platelet count prior cutaneously twice per day) was 71 percent (32 of 45 pregnancies) and
to or at delivery as measurements are fraught with error; however, if the 42 percent (19 of 45 pregnancies) with low-dose aspirin alone (odds
fetal platelet count is known to be less than 20,000/μL, cesarean section ratio: 3.37 [95% confidence interval: 1.40 to 8.10]). A rarer acquired
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is probably reasonable. Newborns of mothers with ITP should be mon- cause of fetal loss and thrombosis in pregnancy is paroxysmal nocturnal
itored for 5 to 7 days after delivery to ensure that the platelet count does hemoglobinuria (PNH; Chap. 40). Though no clinical trials data exist,
not drop (Chap. 117). recommendations are to provide prophylactic or intermediate-dose
low-molecular-weight heparin antepartum and for 6 weeks postpartum.
Eclampsia and HELLP Syndrome Eculizumab should be consider both prior to and following delivery. 76
The spectrum of hypertensive disorders of pregnancy ranging from Although an association between inherited thrombophilias and
preeclampsia to severe preeclampsia and HELLP syndrome to eclamp- pregnancy loss has been elusive and there are inconsistencies between
sia (see Chap. 51) may also result in thrombocytopenia, although studies, there is an association between factor V Leiden and recurrent
thrombosis is more of an issue than is bleeding. There is some debate fetal loss. 77,78 Less-convincing data exist for prothrombin 20210A, but
in the literature as to whether thrombocytopenia can be diagnosed in there is no clear association with homozygous methylene tetrahydro-
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preeclampsia without HELLP syndrome; however, data from one large folate reductase C677T polymorphism (hyperhomocysteinemia).
study indicated that approximately 15 percent of cases of preeclamp- Clinical trials examining the use of low-molecular-weight heparins
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sia are complicated by thrombocytopenia. In general, the symptoms of or aspirin to prevent adverse pregnancy outcomes in women with
preeclampsia, including hematologic manifestations, resolve with deliv- inherited thrombophilias have been criticized for lack of an untreated
ery; however, in a small proportion of cases they persist, worsen, or even control group. 80–82 Pregnancy outcomes from a large ongoing trial con-
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develop immediately postpartum. When symptoms persist postpartum, ducted with a no-treatment control have yet to be published. Studies

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