- 作者：Robert L. Andres ; MDa ; Annette Miles ; MD ; MPHb
- 刊名：Obstetrics and Gynecology Clinics of North America
- 出版年：2001
- 出版时间：1 September 2001
- 年：2001
- 卷：28
- 期：3
- 页码：613-630
- 全文大小：1162 K
Pregnancy is a recognized risk factor for VTE. Each component of Virchow's triad (hypercoagulability, venous stasis, and vascular damage) is present in the pregnant woman. Pregnancy is also accompanied by numerous changes in the coagulation system. Increases in fibrinogen and several clotting factors (including factors I, II, VII, VIII, IX, and XII) are well documented. Evidence also suggests a heightened inhibition of fibrinolytic activity, with increases in plasminogen activator inhibitors I and II. Venous stasis is apparent as pregnancy progresses and is frequently attributed to an increase in venous capacitance (progesterone related) and compression of the inferior vena cava by the gravid uterus. Additional risk factors for the development of VTE during pregnancy include cesarean delivery, which is associated with five- to tenfold increase in the incidence of VTE.
Pregnant women who have sustained a thrombus during a previous pregnancy or while taking combination oral contraceptives are thought to be at risk (7.5 % to 12 % ) for a recurrent thromboembolic event.
Over the past decade, understanding of the contribution of acquired and hereditary thrombophilias to pregnancy-related VTE has increased. Girling and deSwiet reported an eightfold increase in the risk of VTE during pregnancy in women with heritable and acquired coagulopathies. The most common acquired thrombophilia is the antiphospholipid syndrome, characterized by thrombosis, thrombocytopenia, and pregnancy loss. Patients with circulating antiphospholipid antibodies are at increased risk for venous and arterial thrombosis. One study reported that 22 % of patients with antiphospholipid syndrome had a venous thrombosis, whereas Branch and co-workers reported that the risk of thromboembolism during pregnancy was 5 % . Recurrent thrombosis is common in patients with antiphospholipid syndrome, with one study noting recurrent thromboses in 69 % of patients.
Numerous hereditary thrombophilic conditions have been described, including antithrombin II deficiency, protein S and C deficiencies, factor V (Leiden) mutation, prothrombin mutation (G20210A), hyperhomocystinemia, and resistance to activated protein C. The general risk of pregnancy-related VTE in women with a hereditary thrombophilia is shown in .
Other reported risk factors for thrombosis include obesity, ethnicity, maternal age, parity, prolonged bed rest, infection, and trauma. Despite these recognized risk factors, Gherman and co-workers found that less than one third of their study group (53 of 165) had a known risk factor for VTE.
Most early reports concluded that the risk of VTE was greatest in the late third trimester and the postpartum period. More recent studies suggest that the risk of VTE is greatest in the antepartum period. Gherman and colleagues described 165 episodes of VTE (127 cases of DVT and 38 cases of pulmonary embolism) among more than 268,000 deliveries at a single institution (1978 through 1996). Among the 127 patients with DVT, 94 cases were detected in the antepartum period (mean gestational age, 16.8 ¡À 2.4 weeks). The diagnosis was made before 15 weeks' gestation in half (n = 47) of the cases and after 20 weeks in 28 patients. Available data suggest that pulmonary embolism is diagnosed more frequently in the postpartum period, especially following cesarean delivery. In the aforementioned study, of the 38 cases of pulmonary embolism, 23 were diagnosed in the postpartum period, with 19 occurring after cesarean delivery.
The signs and symptoms associated with DVT include pain, tenderness, swelling, a palpable cord, changes in limb color, and a difference between the limb circumference of greater than 2 cm. A recent study of 127 confirmed cases of DVT found that 85.7 % of the patients presented with pain, tenderness, and unilateral leg swelling. Fewer than half of the patients had a positive Homans' sign (46.5 % ), erythema (27.6 % ), a palpable cord (12.6 % ), or warmth (13.4 % ). The clinical diagnosis of DVT is complex; the typical signs and symptoms are neither sensitive nor specific. Haeger and colleagues reported that nearly half of the patients thought to have a DVT based on clinical signs and symptoms had no evidence of thrombus when studied with venography. In a study of patients with angiographically proven pulmonary emboli, more than half were found to have ¡°silent?DVT in asymptomatic limbs.
Given the tenuous nature of the clinical diagnosis of DVT, various diagnostic tests have been developed to improve the reliability and validity of the diagnosis. Venography has long been considered the definitive diagnostic test for DVT. A thrombus is identified by the observation of a filling defect in more than one radiographic view. The diagnosis is considered when there is sudden termination of a vessel or redirection of blood flow. The test is expensive, invasive, and difficult to interpret unless all of the deep veins are adequately filled with contrast material. The utility of venography is further limited by the inability to perform serial tests, by concerns over fetal exposure to radiation, and by the potential for contrast agents to cause chemical phlebitis and pain. The radiation exposure to the fetus is minimal (0.0005 Gy) and should not prevent the use of venography in cases that are equivocal.
Impedance plethysmography has been widely used in the diagnosis of DVT and compares favorably with contrast venography. The test is sensitive for proximal thrombi but relatively insensitive for thrombi distal to the knee. The use of impedance plethysmography in the pregnant patient has been associated with a high rate of false-positive results attributed to obesity, increased intra-abdominal pressure, and decreased venous return caused by edema of the lower extremity. Hull and co-workers studied impedance plethysmography in 152 pregnant patients with clinical signs and symptoms consistent with DVT. Among 13 patients with abnormal results, 12 had venographic evidence of DVT. The remaining 139 patients were followed up with serial impedance plethysmography, and none of these patients had clinical evidence of DVT or pulmonary embolism.
Real-time ultrasonography (including duplex Doppler) has become the diagnostic test of choice for DVT of the proximal lower extremity. Several studies have suggested that the sensitivity and specificity of this diagnostic modality range from 90 % to 100 % . Lensing and co-workers studied 220 nonpregnant patients with suspected DVT, comparing contrast venography with Doppler ultrasonography. The sensitivity and specificity of the sonographic testing were 100 % and 91 % , respectively.
In general, the diagnosis of DVT in a pregnant woman is best accomplished using noninvasive tests. The McMaster Diagnostic Imaging Practice Guidelines Initiative suggests that either ultrasonography or impedance plethysmography is appropriate as a first-line test in the diagnosis of DVT in the pregnant patient. There is a role for MR imaging in cases of clinical suspicion of DVT when impedance plethysmography and ultrasonography are equivocal.
The diagnosis of pulmonary embolism is equally complex. The most common of the reported signs and symptoms are tachypnea and dyspnea. Approximately 90 % of patients exhibit tachypnea, whereas 80 % complain of dyspnea. Fewer patients present with pleuritic chest pain, apprehension, cough, tachycardia, hemoptysis, or fever. Hypotension and cardiovascular collapse are suggestive of a massive pulmonary embolus. Stiller and colleagues have reported the acute onset of cortical blindness in a patient who was proven to have a pulmonary embolus.
The physical examination is generally unremarkable. Auscultation may reveal a friction rub, rales, or a fixed second heart sound. The patient may have signs of right-sided heart failure, including jugular venous distension, hepatomegaly, and a left parasternal heave. The electrocardiogram is abnormal in 90 % of patients with pulmonary embolus, with the most common abnormality an isolated tachycardia. Nonspecific T-wave changes are seen in as many as 50 % of patients, whereas the classic S1Q3T3 pattern is found in 10 % of cases. The arterial blood gas generally reveals a partial pressure of arterial oxygen (PaO2) of less than 80 mm Hg, although 10 % to 25 % of patients with a proven pulmonary embolism have a PaO2 of greater than 80 to 85 mm Hg on room air.
Imaging modalities used in the diagnosis of pulmonary embolism include chest radiographs, ventilation-perfusion lung scans, pulmonary arteriography, CT, and MR imaging. The chest radiograph is a nonspecific tool in the diagnosis of pulmonary embolism. Seventy percent of patients with a pulmonary embolism have abnormalities noted on chest radiographs. Common findings include elevation of the hemidiaphragm, atelectasis, and pleural effusions. The classic finding of oligemia (increased echolucency as a result of interruption of vascular flow) is seen in 2 % of patients. The chest radiograph serves primarily as a means of eliminating other pulmonary causes of the patient's signs and symptoms.
Ventilation-perfusion scintigraphy is considered the first-line diagnostic tool in evaluating the patient with a clinical suspicion of pulmonary embolism. This noninvasive nuclear medicine study is interpreted as negative (normal), or as having low, intermediate, or high probability. A normal study has a negative predictive value of greater than 99 % , with a prevalence of pulmonary embolism of less than 0.2 % . Other investigators have shown that the likelihood of a pulmonary embolism with a low-probability scan is less than 5 % . A high-probability scan is extremely helpful to the clinician given the positive predictive value of 97 % . Nevertheless, most scans (70 % ) are interpreted as either intermediate probability or indeterminate probability (coexisting pulmonary disease with or without chest radiographic abnormalities). In this group of patients (with essentially a nondiagnostic ventilation-perfusion scan), the prevalence of pulmonary embolism is 25 % . These patients present the greatest challenge and can be assessed further with pulmonary angiography, CT, or MR imaging.
Pulmonary angiography has long been viewed as the gold standard in the diagnosis of pulmonary embolism, with sensitivity and specificity approaching 95 % . The significant risk of morbidity (3 % to 5 % ) and even mortality (0.3 % to 0.5 % ) has led to the development of helical or spiral CT and electron-beam CT as less invasive alternatives to angiography. Interested readers are referred to a recent review.
Timely diagnosis and treatment of pulmonary embolism are of utmost importance given the associated morbidity and mortality. The mortality rate for untreated pulmonary embolism is near 30 % ; the institution of appropriate anticoagulant therapy reduces the mortality rate to 3 % .