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Anticoagulants and Thrombolytics in Pregnancy

Practice Essentials

The use of anticoagulants and thrombolytics in pregnancy is an important consideration; pregnancy is associated with a 5-fold increase in the risk of venous thromboembolism (VTE), with the risk rising to 20-fold or more during puerperium.
The risk further increases if an underlying thrombophilia is present. The risk of VTE persists until nearly 12 weeks postpartum.

Indications for antithrombotic agents

Anticoagulant therapy is indicated in pregnancy for the treatment of acute VTE and valvular heart disease, as well as for the prevention of pregnancy-related complications in women with antithrombin deficiency, antiphospholipid antibody (APLA) syndrome,
or other thrombophilias who have had a prior VTE.
Low molecular weight heparins (LMWHs) are the preferred agents in women with confirmed VTE; alternative agents that may be considered are unfractionated heparin (UFH) and possibly fondaparinux.
In women at high risk for pregnancy-related VTE, LMWHs and UFH may be considered.

Etiology of thrombosis in pregnancy

Normal pregnancy is associated with a hypercoagulable state, which arises from the following:

Increased serum levels of procoagulants: Including fibrinogen and factors II, VII, VIII, X, and XII

Decreased protein S levels

Increased resistance to activated protein C: Observed in the second and third trimesters of pregnancy

Increased serum plasminogen activator inhibitor-1 (PAI-1) and placental PAI-2 levels: Lead to a decreased fibrinolytic state

Venous stasis: Resulting from pressure of the gravid uterus on the inferior vena cava and decreased venous tone

The risk of pregnancy-related VTE is particularly high in heterozygous carriers of factor V Leiden (4-fold to 16-fold increase)
or the prothrombin mutation (15-fold increase),
as well as in women with APLAs (5% incidence).

Anticoagulation in pregnant patients with valvular heart disease

Warfarin is more efficacious than unfractionated heparin (UFH) for thromboembolic prophylaxis of pregnant women with mechanical valves.
Unfortunately, warfarin therapy in the first trimester of pregnancy is associated with a substantial increase in fetal anomalies, and anticoagulation with any agent is associated with an increased incidence of fetal wastage (approximately 30%), prematurity (approximately 45%), and low birth weight (approximately 50%).

Complications secondary to anticoagulation during pregnancy

Fetal complications

Warfarin crosses the placenta and can cause fetal bleeding (including intracranial hemorrhage) and teratogenicity, with the latter occurring mainly during the first trimester.
Neither UFH nor low ̶ molecular weight heparin (LMWH) cross the placenta; therefore, these agents do not cause fetal bleeding or teratogenicity, although bleeding at the uteroplacental junction and fetal wastage are possible. As there is little information on maternal and fetal safety of direct oral anticoagulants, these are avoided in pregnancy. 

Maternal complications

Major bleeding in patients treated with UFH therapy (2%)

Heparin-induced thrombocytopenia (3%) (HIT)

Vertebral fracture from heparin-induced osteoporosis (2-3%)

Significant reduction in bone density from long-term UFH therapy (about 30%); LMWH causes less osteoporosis, including less heparin-induced osteoporosis, than does UFH

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