studies indicate that DOACs are secreted into
therapy in pregnancy?
VKAs cross the placenta and can cause teratogenicity, pregnancy loss, fetal bleeding, and neu-rodevelopmental deficits. Therefore, discontinuation of VKAs prior to the sixth week of gestation is
necessary to avoid warfarin embryopathy. DOACs
have been shown to readily cross the placenta
but with unknown human reproductive risks.
Fondaparinux, a synthetic pentasaccharide, crosses the placenta in small quantities. Though there
are reports of the successful use of fondaparinux
in pregnancy, there is limited reported experience of its use in the first trimester.86
The risk for bleeding with anticoagulation is
notably acceptable. In a case-control study of 88
pregnant women receiving therapeutic-dose anticoagulation, the risk of postpartum hemorrhage
(PPH) after vaginal delivery was 30% in those who
received LMWH anticoagulation versus 18% in
those who did not (OR 1. 9 [95% CI 1. 1 to 3. 5]).87
However, the risk for severe PPH (≥ 500 mL) was
similar ( 5.6% versus 5.0%; OR 1. 1 [95% CI 0.4
to 3. 6]). The risk for PPH after cesarean section
was 12% in LMWH users versus 4% in LMWH
non-users (OR 2. 9 [95% CI 0.5 to 19. 4]). The risk
for PPH associated with delivery within 24 hours
after the last dose of LMWH was 1. 2 times higher
(95% CI 0.4 to 3. 6) compared to a longer interval.
Therefore, therapeutic LMWH increases the risk
for blood loss after vaginal delivery, but not the
risk for severe PPH. The risk for PPH is influenced
by the interval between the last dose of LMWH
and delivery. Of note in this study, per the institution’s protocol, the anticoagulation was stopped
with signs of labor or determination of need for
delivery. The risk for blood loss may be mitigated
in more planned delivery scenarios.87
CASE 4 CONTINUED
The patient is placed on prophylactic-dose
LMWH with good tolerance and delivers at 39
weeks' gestation via caesarian section due to non-progression of labor. Postpartum she is restarted
on prophylactic-dose anticoagulation with LMWH.
Two weeks after discharge from the hospital, she
presents with right calf pain and mild shortness
of breath. On physical exam, her leg circumferences are equal. A D-dimer assay is 3375 ng/mL
(normal 0–229). CUS of the right leg shows a
complete occlusive DVT of the mid-distal superficial femoral and popliteal veins and partially occlusive acute DVT of the right posterior tibial and
peroneal veins. CTPA reveals a right lower lobe PE.
Because she had developed VTE despite prophylactic LMWH, her anticoagulation is changed to
therapeutic dose. She is treated with anticoagulation with LMWH for a total of 3 months, after
which a repeat CUS shows no residual thrombosis.
and LMWH during pregnancy?
A prospective study of 14 pregnant women
receiving UFH prophylaxis found that a
prophylactic dose of 5000 units twice a day was
inadequate to achieve prophylactic heparin levels
in any patient in the second or third trimester.88
Similar to treatment dosage, there is no consensus evidence for prophylactic dosing, and dosage
recommendations are based on expert opinion.
In a retrospective study of 25 pregnant women
on intermediate-dose UFH, the mean UFH dose
required to achieve a target anti-factor Xa level
of 0.1 to 0.3 units/mL was 236.9 units/kg/day.89
However, the use of anti-factor Xa levels for
monitoring is controversial as there is no data to
support a difference in outcomes with its use in
prophylactic or therapeutic dosing.
The timing of the previous VTE history is important when deciding on the anticoagulant dose
in pregnancy. In pregnant women with a VTE
that occurred within the previous 4 to 6 weeks,
full-dose anticoagulation with LMWH should be
considered; an intermediate dose (three-fourths
of a therapeutic dose) may be used if the thrombotic episode occurred more than 6 weeks earlier
but still within a year. Prophylactic dosing may be