Thromboembolic Disorders

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Thromboembolic disease is the leading cause of nonobstetric postpartum maternal mortality. In the United States, one half of all thromboembolic events in women younger than 40 years are related to pregnancy. The risk of deep vein thrombophlebitis (DVT) during pregnancy has been reported to be five times higher than in nonpregnant individuals and is probably even higher in the immediate postpartum period. The risk of pregnancy-associated thromboembolism is further increased in patients with prior DVT or Pulmonary embolism (PE), advanced maternal age, multiparity, prolonged bed rest, varicose veins, or obesity, as well as those with a variety of inherited or acquired coagulation disorders. Postpartum risks are increased by cesarean delivery (a fourfold to tenfold increase over vaginal delivery).

The diagnosis of deep vein thrombophlebitis or Pulmonary embolism may be suspected clinically but usually requires radiographic confirmation. Noninvasive methods include high-resolution compression ultrasonography coupled with color Doppler imaging and impedance plethosmography to assess for DVT, as well as ⁹⁹Tc ventilation-perfusion lung scan to assess for PE. Given the 15% to 40% mortality of untreated maternal PE, if results of noninvasive testing are not definitive or if therapy will be altered by an invasive diagnostic procedure (such as pulmonary angiogram), the benefits of the procedure outweigh the risks to mother and fetus. The only examination contraindicated during pregnancy is ¹²⁵I-fibrinogen scanning, because the dose of radiation to the fetal thyroid is clinically significant.

Initial treatment of acute venous thrombosis and Pulmonary embolism requires intravenous heparin given in a high dosage sufficient to prolong the activated partial thromboplastin time (PTT) 1.5 to 2.5 times the control value. The heparin requirements to treat acute venous thrombosis seem to be greater during pregnancy than in the nonpregnant state. In addition, failure to reach adequate anticoagulation in the first 24 hours of treatment greatly increases the risk of recurrent thrombosis. Therefore an initial intravenous bolus of 7500 to 10,000 units is administered, followed by a continuous infusion of heparin at 15 to 20 U/kg/hr. Intravenous treatment is usually continued for 5 to 10 days to allow for organization and firm attachment of the thrombus to the vessel wall. The patient then begins self-injected, adjusted high-dose subcutaneous heparin every 8 to 12 hours. The dose is determined by dividing the 24-hour intravenous required dose into two to three subcutaneous injections daily. The goal again is to maintain the midinterval PTT at 1.5 to 2.5 times the control value. Alternatively, continuous infusion of heparin can be arranged for the patient. Anticoagulation is continued throughout pregnancy and for approximately 3 months postpartum. Though heparin is the anticoagulant of choice during pregnancy, heparin-induced thrombocytopenia and osteoporosis are important adverse effects that must be watched.

There are insufficient data to conclude which regimen provides the safest maximal protection against recurrent antepartum thrombosis. Antepartum thromboembolism prophylaxis should be considered, however, in pregnant women with a prior history of DVT or PE; women with antithrombin III, protein C, or protein S deficiency; and women with the antiphospholipid antibody syndrome.

Unlike heparin, warfarin freely crosses the placenta. Use of warfarin during the first trimester has been associated with a variety of neonatal malformations, including nasal hypoplasia, frontal bossing, and short stature with stippled epiphyses. Use during the second and third trimesters has been associated with central nervous system abnormalities and fetal and placental hemorrhage resulting in fetal death. Warfarin should be avoided throughout pregnancy, and patients already taking warfarin and desiring to conceive should be switched to heparin before conception.

Low-molecular-weight heparin may afford some advantages during pregnancy because of its long half-life, which may allow for once-daily dosing. It has been used in a small number of pregnant women who have had adverse reactions to heparin, and it does not appear to cross into fetal circulation. There are limited data, however, and its use cannot be recommended at this time.

Heparin appears to be safe for use during lactation because it does not enter breast milk. Warfarin also appears to be safe in women who breastfeed their infants. Small studies have found little or no warfarin activity in breast milk or infant’s plasma.

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