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Venous thromboembolism includes deep venous thrombosis (DVT) and pulmonary embolism (PE) and is the leading cause of maternal morbidity and mortality in industrialized nations. Compared with nonpregnant women, the risk of venous thromboembolism increases fivefold during pregnancy and is increased by 60-fold in the first 3 months after delivery.1,2
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Pregnancy-related hypercoagulability is due to increased levels of clotting factors, increased platelet and fibrin activation, and decreased fibrinolytic activity, all of which are adaptations to prevent maternal hemorrhage. Physiologic changes include venous stasis, decreased venous outflow, and uterine compression of the inferior vena cava and iliac veins (particularly the left common iliac and left leg veins). Clots tend to develop in the deep venous system of the legs and pelvis, which includes the internal iliac, femoral, greater saphenous, and popliteal veins. Up to 24% of DVTs are complicated by PE, so early DVT diagnosis is important.1-6
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RISK FACTORS AND CLINICAL FEATURES
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Physiologic signs and symptoms of thromboembolic disease, such as tachycardia, tachypnea, lower extremity edema, and dyspnea are nonspecific and also occur during normal pregnancy. Predictive scoring criteria, such as Wells criteria, have not been validated in pregnant women, but left leg symptoms, calf circumference difference ≥2 cm, and leg symptoms in the first trimester are associated with DVT. Iliac vein thrombosis often presents with unilateral swelling of the entire leg and groin or back pain.
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A personal or family history of thrombosis is an important risk factor. Other major risk factors include thrombophilias (not identifiable at the first presentation), obesity, maternal age >35, smoking, sickle cell disease, diabetes, hypertension, immobility, in vitro fertilization (greater risk for twins than for singleton), and preeclampsia. Cesarean delivery and postpartum complications further increase the risk.1,4,5
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DIAGNOSIS OF DEEP VENOUS THROMBOSIS
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Compression or duplex US is the test of choice, with a reported sensitivity and specificity for detecting proximal DVT in nonpregnant patients of 89% to 96% and 94% to 99%, respectively.7 Compression US is less accurate for isolated calf and iliac vein thrombosis. MRI, either with or without contrast venography, is highly sensitive and specific for the diagnosis of pelvic and iliac vein thrombosis. MRI without contrast is preferred with the addition of contrast only if absolutely needed.8,9 Impedance plethysmography and CT scan of the pelvis are alternatives to diagnose iliac vein thrombosis if MRI is not available. Impedance plethysmography is not widely available and requires operator expertise. CT exposes the fetus to radiation, and iodinated contrast media may affect fetal thyroid tissue.1 If imaging resources are limited, venography with pelvic shielding is another option.10
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d-dimers are not useful to include or exclude DVT or PE because levels progressively increase throughout pregnancy, and venous thromboembolism has been reported with negative d-dimers.11 See chapter 56, Venous Thromboembolism, for a detailed discussion of d-dimers.
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DIAGNOSIS OF PULMONARY EMBOLISM
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Pregnant women with symptoms suggestive of PE and compression US results positive for DVT should receive anticoagulation without waiting for further confirmatory diagnostic studies.
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Women with normal findings on US with suspicion of PE require further diagnostic imaging. The major options for definitive imaging are chest CT–pulmonary angiography and pulmonary perfusion scanning. As of this writing, the fetal and maternal radiation dose with either modality is felt to be within acceptable limits.1,12 Typically, in most institutions, a consensus is obtained between emergency physicians, obstetricians, and radiologists in deciding the imaging steps. Table 100–1 lists advantages and disadvantages of different imaging modalities.
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Consensus documents based on expert opinions of pulmonologists and radiologists recommend a plain chest radiograph first.14 If the chest radiograph is abnormal, or the patient has chronic pulmonary disease, asthma, or chronic obstructive pulmonary disease, chest CT–pulmonary angiography is preferred.14 If the chest radiograph is normal, a negative perfusion scan can be relied upon to exclude the diagnosis of PE, but an inconclusive perfusion scan will then require a chest CT.1,12,14,15
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Magnetic resonance angiography (MRA) can detect PE, but its use in pregnancy has not been well studied. Institutions in which MRA of the pulmonary vasculature is performed routinely have demonstrated a sensitivity of 78% and specificity of 99% when the study is qualified as technically adequate.16
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TREATMENT OF DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLISM
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Venous thromboembolism during pregnancy is treated with either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) (Table 100–2).1,17,18 UFH and LMWH do not cross the placental barrier. UFH is preferred over LMWH in patients in a hemodynamically unstable condition with PE, patients who are likely to bleed, patients with renal insufficiency, patients in labor, those receiving regional anesthesia, and patients undergoing cesarean delivery. Monitor activated partial thromboplastin times when using UFH.11 Dosing requirements of UFH and LMWH increase due to the physiologic changes of pregnancy. Adverse effects of UFH include uteroplacental hemorrhage, heparin-induced thrombocytopenia, and heparin-induced osteopenia. LMWH has fewer adverse effects and fewer bleeding episodes than UFH, and monitoring with anti–factor Xa levels is needed only in special circumstances. See chapter 239, Thrombotics and Antithrombotics, for further discussion of heparins.
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Fondaparinux is used in the United States for the prevention and treatment of venous thromboembolism in heparin-allergic or heparin-intolerant pregnant patients.1 However, fondaparinux is transported across the placenta in low concentrations, and minimal data exist on maternal-fetal safety.1,18
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Do not prescribe warfarin (Coumadin®) in pregnancy because it crosses the placental barrier, causes CNS abnormalities, and causes warfarin embryopathy (bone and cartilage abnormalities and nasal and limb hypoplasia). Warfarin increases the risk of maternal and fetal hemorrhage, especially during delivery. Warfarin can be given in the postpartum period and is safe in lactation.19,20
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An inferior vena cava filter is indicated when anticoagulation is contraindicated, when an acute embolic event occurs despite anticoagulation, or when acute venous thromboembolism occurs with impending delivery of the fetus.21
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Treatment of Life-Threatening Pulmonary Embolism
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Treatment options include systemic thrombolysis, catheter-guided thrombolysis, and surgical or catheter-guided embolectomy.22-25 Data regarding maternal-fetal outcomes in conditions of maternal extremis are limited to case reports, and catheter-guided thrombolysis and embolectomy require precious time for preparation. Recombinant tissue plasminogen activator (10-milligram bolus, 90-milligram infusion over 2 hours) does not cross the placenta and has a lower rate of hemorrhagic complications and lower mortality rate than do streptokinase and urokinase in the nonpregnant population. Streptokinase (250,000-unit bolus, 100,000 units/h infusion for 24 hours) is also used but with a higher rate of subchorionic hemorrhage, allergic complications, and longer infusion duration than recombinant tissue plasminogen activator. Catheter-directed thrombolysis allows for earlier reperfusion and likely improves long-term pulmonary function compared with systemic therapy.1,22 Fetal loss subsequent to surgical embolectomy is higher than with thrombolysis.23,25