Page 2475 - Hematology_ Basic Principles and Practice ( PDFDrive )

2212 Part XIII Consultative Hematology

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to 95%. However, several pregnancy-associated conditions elevate be initiated. The newer target specific oral anticoagulant should not
D-dimer levels, including preterm labor, placental abruption, and be used during pregnancy until safety data in this population have
hypertension of pregnancy, thus undermining the utility of the test been established.
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somewhat in pregnant women by decreasing its specificity. None-
theless, when normal, the D-dimer assay provides the clinician with
useful information. PROPHYLACTIC ANTICOAGULATION
When lower extremity imaging reveals no evidence of thrombus DURING PREGNANCY
in a pregnant woman with suspected pulmonary embolism (PE), the
clinician has several options. Helical CT has become the standard Given the prothrombotic state associated with pregnancy itself, pro-
modality for the diagnosis of PE in nonpregnant individuals at many phylactic anticoagulation should be considered in pregnant women
centers. However, even with abdominal shielding, the procedure with a history of VTE. Recurrence rates for VTE during pregnancy
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results in fetal radiation exposure (approximately 16 mrad) because may be as high as 12% based on the results of retrospective studies.
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of internal scatter. Although this low level of radiation exposure Conversely, Brill-Edwards and colleagues prospectively studied
probably does not cause harm to the fetus, repeated imaging during 125 pregnant women with prior VTE in a study that excluded
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the course of pregnancy is to be avoided. Ventilation/perfusion women with known thrombophilia. Study subjects did not receive
(V/Q) scanning is frequently used in the evaluation of pregnant prophylactic anticoagulation during the antenatal period, but they
women with suspected PE but has limitations as well. Results of a did receive anticoagulation therapy for 4 to 6 weeks postpartum. The
prospective study indicate that when used in this patient population, authors documented a VTE recurrence rate of 2.4%. Women who
V/Q scanning infrequently yields a conclusively positive result (1.8% had a temporary risk factor at the time of their initial VTE event
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of cases) and is often nondiagnostic (24.8% of cases). Finally, and lacked laboratory evidence of an underlying hypercoagulable
pulmonary angiography can be used in the evaluation of PE in rare disorder at the time of study enrollment experienced no recurrences
instances when the previously described diagnostic tests yield nondi- during pregnancy. On the basis of the results of this study, routine
agnostic results in the face of a high clinical suspicion. prophylactic anticoagulation for women with a single previous
VTE in pregnancy is treated with heparin. Until LMWH was VTE event is not recommended. However, patients with a known
introduced in the late 1980s, UFH was the anticoagulant of choice hypercoagulable state, those with multiple previous VTE events,
for treatment of pregnant women with VTE. Because it does not cross and those considered high risk for recurrent VTE should receive
the placenta, UFH is nonteratogenic. However, drawbacks to UFH prophylactic anticoagulation during pregnancy and for 4 to 6 weeks
therapy, including heparin-associated osteoporosis, HIT, and the postpartum. As previously discussed, prophylactic anticoagulation
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drug’s unpredictable pharmacokinetics, are well documented. can be discontinued at parturition and reinitiated 6 to 12 hours
Heparin-associated osteoporosis can develop in women who receive postpartum.
at least 1 month of therapy; it is likely related to a toxic effect of The management of pregnant women with prosthetic heart valves
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heparin on osteoblasts. Because of its more favorable side effect is controversial and deserves special attention, although a full review
profile, reliable pharmacokinetics, and equal efficacy in treating VTE, of the topic is beyond the scope of this review. Coupled with the
LMWH now represents the most commonly used anticoagulant for prothrombotic physiology of pregnancy, the presence of a prosthetic
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treatment of VTE in pregnancy. The risk of osteoporosis and HIT valve places such women in an ultra-high-risk category. Before the
appears to be less with LMWH-based anticoagulation than with introduction of LMWH, options for anticoagulation in this patient
UFH-based anticoagulation. 203,204 Although practice patterns vary, it population included (1) warfarin throughout pregnancy; (2) warfarin
is reasonable to base the initial dose of LMWH on early pregnancy with UFH during weeks 6 to 12, the period of major organogenesis;
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(rather than current) weight. Because clearance of LMWH increases and (3) UFH throughout pregnancy. More recently, LMWH has
during pregnancy, twice-daily dosing regimens are preferred to once- been used in this setting, although its safety and efficacy have been
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daily regimens. In terms of duration of therapeutic anticoagulation, questioned on the basis of several studies. Overall, a lack of rigorous,
many clinicians continue therapy at full dose through the entire comparative studies hinders evidence-based management of women
pregnancy and puerperium based on the rationale that pregnancy with prosthetic heart valves. Current recommendations allow for one
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itself represents a risk factor for recurrent VTE. In contrast, other of three therapeutic strategies, initiated after a thorough discussion
clinicians advocate initial anticoagulation with full-dose LMWH for of risks and benefits with the patient: (1) warfarin, with LMWH or
a designated period followed by conversion to an intermediate dose. UFH substituted during weeks 6 to 12; (2) dose-adjusted UFH
This approach may be beneficial for individuals susceptible to side throughout pregnancy; or (3) dose-adjusted LMWH throughout
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effects of anticoagulation such as bleeding or osteoporosis. The risk pregnancy. 186
of significant bleeding with LMWH during pregnancy is estimated
to be around 2%.
Warfarin is contraindicated in pregnant women. It crosses the THROMBOPHILIA AND PREGNANCY
placenta and can cause both fetal hemorrhage and nervous system
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abnormalities and other teratogenic effects. Warfarin can be used Thrombophilias, inherited and acquired, increase the risk of VTE in
in the postpartum period after initiating therapy with concurrent pregnant women and adversely affect pregnancy outcomes. Included
heparin and in this setting does not appear to increase the risk of within this category of diseases are factor V Leiden, prothrombin
bleeding in children of lactating mothers. 196 gene polymorphisms, antiphospholipid antibody syndrome, anti-
Anticoagulation should be discontinued at the time of parturition. thrombin deficiency, and protein S and C deficiency. In addition,
UFH and LMWH should, in most circumstances, be stopped 12 to hyperhomocysteinemia and methylenetetrahydrofolate reductase
24 hours before delivery. If the risk of recurrent VTE is particularly C677T mutation have been studied. There are varied results when
high in a woman receiving LMWH, the clinician can convert to assessing the literature in regard to the risk of pregnancy-associated
intravenous UFH and treat until 4 to 6 hours before delivery, mini- VTE in the setting of an inherited thrombophilia. Authors of a 2005
mizing the time off anticoagulation. meta-analysis reviewed the risk of VTE during pregnancy by the
The risks of regional anesthesia must be weighed carefully in specific thrombophilia present. The inherited thrombophilias (with
women receiving anticoagulation because therapy increases the likeli- the exception of MTHFR mutation) were associated with a statisti-
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hood of bleeding, hematoma formation, and potential neurologic cally significant increase in the risk of VTE during pregnancy.
compromise. In a woman undergoing elective delivery with discon- Because the overall incidence of VTE in pregnancy is low, however,
tinuation of anticoagulation 12 to 24 hours prior, epidural anesthesia in women without a history of thrombosis, the absolute risk conferred
may be used. UFH or LMWH may be reinitiated 6 to 12 hours after by thrombophilias is generally low. The positive predictive value of
delivery or after removal of the epidural catheter. Then, after thera- factor V Leiden heterozygosity was 1 in 500. Prothrombin heterozy-
peutic levels of UFH or LMWH have been achieved, warfarin may gosity was 1 in 200. Women with homozygosity for these mutations,