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

evaluating a role for inherited thrombophilias in preeclampsia and prophylactic or intermediate dose low molecular weight heparin for 6
intrauterine growth retardation indicate that these factors may not be weeks. For pregnant women with a low risk of recurrence (e.g., a single
causative, but may contribute to disease severity. 80,81 VTE with a transient risk factor unrelated to pregnancy or estrogen use)
surveillance is recommended antepartum, whereas those with higher
THROMBOEMBOLIC EVENTS risk should receive prophylactic or intermediate dose low molecular
weight heparin prior to delivery. Women with no prior VTE are divided
Risk Factors into four categories. Those with higher risk of VTE in pregnancy includ-
Estimates place the relative risk of arterial and venous thromboem- ing Factor V Leiden or Prothrombin 20210 homozygotes or compound
bolism (VTE) in pregnant women (Chaps. 133 and 134) at two to six heterozygotes with a family history of VTE should receive prophylac-
times that of nonpregnant women. 11,82 Factors specific to pregnancy that tic or intermediate dose low molecular weight heparin antepartum
increase the risk of VTE include obstruction of venous return by the and postpartum prophylaxis with prophylactic or intermediate dose
gravid uterus, acquired prothrombotic changes in hemostatic proteins, low molecular weight heparin for 6 weeks. Factor V Leiden or Proth-
and venous atonia caused by hormonal factors. Additional risk factors rombin 20210 homozygotes or compound heterozygotes without a fam-
84
include cesarean section (especially emergency), obesity, and increasing ily history of VTE should undergo surveillance antepartum and should
age. Approximately 80 percent of deep vein thromboses in pregnancy receive postpartum prophylaxis with prophylactic or intermediate dose
occur in the iliofemoral veins on the left, probably as a consequence low molecular weight heparin for 6 weeks. Pregnant women with no
of compression of the left iliac vein by the right iliac and ovarian personal history of VTE with any other thrombophilia and a family
arteries. 85,86 Rates of VTE immediately postpartum are difficult to assess history of VTE should undergo surveillance antepartum and should be
as many occur after the patient is discharged; one large study estimates offered postpartum prophylaxis with prophylactic or intermediate-dose
rates as much as 5 times higher in postpartum women than pregnant low-molecular-weight heparin for 6 weeks. Finally, women with lower
women. Inherited thrombophilias (Chap. 130) are associated with risk thrombophilias and no personal or family history of VTE should be
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more than half of VTE in pregnancy. Factor V Leiden and the proth- offered surveillance post antepartum and postpartum. Patients with two
rombin gene mutation are the commonest abnormalities associated or more episodes of VTE should probably be treated throughout preg-
with VTE in pregnancy, accounting for 44 and 17 percent, respectively. nancy and the puerperium. 98–102 As noted above, women who meet the
In general 1 in 500 factor V Leiden heterozygotes and 1 in 200 heterozy- criteria for antiphospholipid antibody syndrome should receive ante-
gous carriers of the prothrombin 20210 gene mutation will have a VTE partum prophylactic or intermediate dose unfractionated or prophy-
in pregnancy. Homozygosity for either of these mutations increases risk lactic low molecular weight heparin and low dose aspirin throughout
about fourfold. Based on recent studies, the risk for VTE during preg- pregnancy. Treatment of VTE in pregnancy should be with full-dose
nancy is 1 in 113 for protein C deficiency, approximately 1 in 3 for type I low-molecular-weight heparin. Ideally, women on treatment doses of
antithrombin deficiency, and 1 in 42 for type II antithrombin deficiency. heparin have elective induction of labor. Heparin is usually discontin-
Risk for carriers of protein S deficiency is similar to that for protein C ued 24 hours prior to induction; however, women deemed to be at very
deficiency. 88–90 high risk of recurrent VTE can then receive intravenous heparin up to
4 to 6 hours prior to delivery. 100,101 Great care should be taken with epi-
Diagnostic Methods dural anesthesia, and it should be avoided if there is any question of a
Diagnosis of VTE in pregnancy is complicated both because the significant anticoagulant effect. Heparins and warfarin are safe postpar-
presenting complaints—leg edema, back pain, and chest pain—are tum, even when breastfeeding. 103
common in pregnancy, and because radiologic studies used to make
the diagnosis in nonpregnant individuals are relatively contraindicated TREATMENT OF HEMATOLOGIC
in pregnant women. Compression ultrasonography is the initial test of
choice in pregnant women. If this test is nondiagnostic, several other MALIGNANCIES IN PREGNANCY
tests may be considered. If pulmonary embolus is suspected, lung ven-
tilation perfusion scanning, which gives relatively low-dose radiation, Although not common, leukemias and lymphomas do occur in preg-
may be used. Magnetic resonance imaging or magnetic resonance nancy and present problems with proper diagnosis, staging, and treat-
venography are also informative if available. Measurement of D-dimers ment (Chaps. 88–90). The literature suggests that the incidence of
is a useful adjunct in nonpregnant patients to rule out VTE (D-dimers Hodgkin lymphoma is 1:1000 to 1:6000 pregnancies, whereas the inci-
104
are sensitive, but not specific, for VTE). However, D-dimer levels rise dence of non-Hodgkin lymphoma is manyfold lower. Leukemia in
over the course of normal pregnancy 91,92 and with several complications pregnancy is uncommon.
of pregnancy, including preterm labor, hypertension, and placental
abruption, and thus may not be useful in excluding VTE. HODGKIN LYMPHOMA
93
Neither the histology nor the outcome of patients who present during
Prophylaxis pregnancy is worse than that of other patients. Diagnosis, usually by
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Prophylaxis for VTE is a controversial issue as only a few prospective biopsy of a lymph node, is usually not problematic, but staging can be
studies have been done to assess the risk of use. 94,95 There is general difficult. Posterior–anterior chest films with abdominal shielding and
agreement, however, that because of its teratogenic potential, warfarin marrow biopsy (in the presence of B symptoms, leukopenia, or throm-
should not be used during pregnancy and that low-molecular-weight bocytopenia) should be done and present little risk to the fetus. Labo-
heparins are the anticoagulant of choice because they do not cross the ratory studies, including blood counts, liver functions tests, and ESR,
placenta and have a lower risk of osteoporosis and heparin-induced should be done, but care should be taken in interpreting the alkaline
thrombocytopenia than unfractionated heparin. Most experts now phosphatase and ESR measurements, which both rise during the course
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agree that risk assessment should be based on both personal and fam- of a normal pregnancy. Evaluation for the presence of abdominopelvic
ily history of VTE as well as the presence of a known hypercoagula- disease is difficult because computed tomography imaging is contrain-
ble state. Based on the most recent Chest Guidelines, all women with dicated in pregnant women. Abdominal ultrasonograms are safe, but
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prior history of VTE should be offered postpartum prophylaxis with provide limited information. If necessary, magnetic resonance imaging

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