INTRODUCTION — Pregnancy and the puerperium (postpartum period) are well-established risk factors for venous thromboembolism (VTE), with VTE occurring in approximately 1 in 1600 pregnancies [1-3].
VTE can manifest during pregnancy as an isolated lower extremity deep venous thrombosis (DVT) or clot can break off from the lower extremities and travel to the lung to present as pulmonary embolus (PE). In the United States, PE is the sixth leading cause of maternal mortality [4-7]. Preventing deaths from PE in pregnancy requires a high index of clinical suspicion focused on an accurate diagnostic approach so that appropriate treatment with anticoagulation can be initiated in a timely fashion.
The diagnosis of PE during pregnancy will be reviewed here. The epidemiology and pathogenesis of VTE, the diagnosis of DVT during pregnancy, and the prevention and treatment of DVT and PE during pregnancy are discussed separately. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis" and "Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention" and "Deep vein thrombosis and pulmonary embolism in pregnancy: Treatment".)
CLINICAL PRESENTATION — There are no clinical signs or symptoms that are specific for PE. This nonspecific presentation is magnified during pregnancy due to an overlap between symptoms seen in patients with PE and those associated with the normal physiologic changes of pregnancy (eg, dyspnea occurs in up to 70 percent of normal pregnancies) [8]. Thus, identifying a clinically important PE during pregnancy is challenging, and it is imperative that clinicians understand the potential for both overdiagnosing and underdiagnosing PE during pregnancy. (See "Clinical manifestations and diagnosis of early pregnancy", section on 'Clinical manifestations of early pregnancy' and "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes" and "Maternal adaptations to pregnancy: Dyspnea and other physiologic respiratory changes".)
PE has a wide variety of presenting features, ranging from asymptomatic to shock or sudden death. Pregnant patients were excluded from the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) study that described signs and symptoms of PE in nonpregnant patients [9]. However, smaller trials suggest that the presenting features in pregnant patients are similar to those reported in PIOPED II [10-12]. As an example, in a study of 38 pregnant women with confirmed PE, dyspnea (62 percent), pleuritic chest pain (55 percent), cough (24 percent), and sweating (18 percent) were the four most common presenting features [10]. In an observational study from the United Kingdom that included 198 pregnant or postpartum women with diagnosed PE, dyspnea at rest was reported in 54 percent, pleuritic chest pain in 52 percent, cough in 9 percent, and hemoptysis in 7 percent [13].
Similar to nonpregnant patients, any one or combination of the following symptoms – acute-onset dyspnea, pleuritic pain, and hemoptysis – should always raise alarm and increase the clinical suspicion for a PE during pregnancy. The clinical presentation of PE in nonpregnant patients is discussed separately. (See "Overview of acute pulmonary embolism in adults", section on 'Clinical presentation, evaluation, and diagnosis'.)
LABORATORY STUDIES — Arterial blood gases, D-dimer levels, and echocardiography are often performed but are neither sensitive nor specific as diagnostic or pretest probability tools for the evaluation of suspected PE during pregnancy.
●Arterial blood gases – For nonpregnant and pregnant patients suspected of having a PE, arterial blood gas analysis is neither sensitive nor specific diagnostically. A respiratory alkalosis is a very common feature of both pregnancy and PE. As in the nonpregnant population, a normal PO2, PCO2, or alveolar-arterial difference is common with PE [14,15]. In one small retrospective study of arterial blood gases in pregnant women with documented PE, 10 of 17 patients (59 percent) had a normal alveolar-arterial difference [16]. Nonetheless, the presence of hypoxemia with a normal chest radiograph should raise clinical suspicion for PE in pregnancy and prompt further evaluation. (See 'Differential diagnosis of PE' below and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Laboratory tests'.)
●D-dimer – D-dimer levels increase during the course of a normal pregnancy and slowly decline postpartum [17-20]. Interpretation of D-dimer levels during pregnancy and the puerperium is complicated by a lack of normal reference ranges in this setting. Thus, D-dimer levels have limited utility for the diagnosis of venous thromboembolism (VTE) in pregnancy. As an example, in a retrospective observational series of 37 pregnant women with suspected PE, when compared with ventilation/perfusion (V/Q) scanning, D-dimer levels assessed by immunoturbidimetric assay (<500 ng/mL) had an estimated sensitivity and specificity of 73 and 15 percent, respectively [21]. Considering the low sensitivity (high false negative rate) and specificity (high false positive rate) of D-dimer in this setting, a high D-dimer is not diagnostic of PE, and a low D-dimer (even <500 ng/mL) only modestly lowers the suspicion but does not effectively eliminate PE from the differential [22,23]. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'Laboratory testing'.)
●Echocardiography – Echocardiography is not routinely performed in the diagnostic evaluation of a pregnant patient suspected of having a PE. Occasionally, an echocardiogram can be performed to exclude pregnancy-related cardiomyopathy or to evaluate the size of the right ventricle (RV) in a patient with confirmed PE. However, the prognostic value of RV dilation by echocardiogram has not been formally evaluated in pregnancy. (See "Overview of acute pulmonary embolism in adults", section on 'Prognosis'.)
IMAGING — PE cannot be definitively diagnosed without confirmatory imaging. The two most common modalities for imaging are lung scintigraphy (ventilation/perfusion scanning [V/Q]) and computed tomographic pulmonary angiography (CTPA). Magnetic resonance pulmonary angiography (MRPA) is not validated, and although contrast-enhanced pulmonary angiography had once been the gold standard for diagnosis of PE, neither test is commonly used in either pregnant or nonpregnant individuals. Employing strategies that use compressive ultrasound (CUS) to avoid the radiation exposure of V/Q and CTPA have been described, particularly in patients with lower extremity symptoms, and a positive diagnosis of DVT on CUS typically precludes the need for confirmatory imaging of the chest.
In this section the diagnostic accuracy of each test is discussed relative to their sensitivity and specificity for the diagnosis of PE associated with pregnancy. The suggested approach to the evaluation of a pregnant patient suspected of having a PE is discussed separately. (See 'Diagnostic algorithm' below.)
Chest radiograph — Findings on chest radiograph are neither sensitive nor specific for PE. Abnormalities on chest radiograph are common in nonpregnant patients with suspected PE, and an abnormal chest radiograph can interfere with the interpretation of further testing (ie, V/Q scan). However, since pregnant women are typically younger and healthier than the general population of patients with a suspected PE, they are more likely to have a normal chest radiograph.
A peripheral infarct might be suggested by a shallow wedge-shaped opacity in the periphery of the lung with its base against the pleural surface (Hampton's hump). However, this sign and other radiographic features (atelectasis, infiltrates) are neither sensitive nor specific for a diagnosis of PE [24,25].
Despite its poor diagnostic accuracy, a chest radiograph should be performed in every pregnant patient in whom a PE is suspected. This both evaluates for alternative diagnoses and allows the accurate interpretation of V/Q scan results. The value of chest radiography for the interpretation of V/Q scans according to the PIOPED II study in nonpregnant patients is discussed separately [26]. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Chest radiograph'.)
V/Q scan — For those with a normal chest radiograph, ventilation/perfusion (V/Q) scanning remains the test of choice for the diagnosis of PE in pregnancy [9,11,12,27-31]. A positive V/Q scan demonstrates a definitive pattern of mismatch between the ventilation and perfusion images of the lung. This is discussed in more detail separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Ventilation perfusion scan'.)
Although the PIOPED II study that evaluated V/Q scanning for the diagnosis of PE did not include pregnant patients, V/Q scan results in pregnancy are stratified into the same risk categories (table 1):
●Normal/very low probability
●Low probability
●Moderate probability
●High probability
In general, only normal or very low probability scans and high probability scans are considered diagnostic [9]. Normal or very low probability scans are associated with a 0 to 6 percent chance of having a PE. In contrast, depending upon the patient population, high probability scans are associated with a 56 to 96 percent chance of having a PE. All other scans are indeterminate.
In the general population, there is a high rate of indeterminate scans due to the high prevalence of abnormal chest radiographs from underlying cardiopulmonary disease. However, since most pregnant women are young, healthy, and without pulmonary pathology, the estimated percentage of normal chest radiographs is expected to be high. Reflecting this likelihood, studies in pregnant women suspected of having a PE suggest that V/Q scanning has a high diagnostic accuracy when the chest radiograph is normal [11,12,27-31]. The vast majority of V/Q scans performed for suspected PE in pregnancy are normal/very low probability and have a high negative predictive value for ruling out the diagnosis of PE in pregnancy. Unlike the general population, pregnant women have a relatively low likelihood of indeterminate V/Q scans and a high likelihood of diagnostic V/Q scans.
Retrospective studies confirm a rate of diagnostic V/Q scans (normal/very low or high probability) that ranges from 75 to 93 percent, and indeterminate scans (low probability/moderate probability) that ranges from 7 to 25 percent, in pregnant patients suspected of having a PE [11,12,28-31].
●In one study of 120 consecutive pregnant patients presenting with suspected PE, 75 percent of V/Q scans were diagnostic (normal and high probability scans: 73.5 and 1.8 percent, respectively) and the remaining 25 percent were nondiagnostic [11]. In the 104 patients who did not receive anticoagulation therapy (80 normal and 24 nondiagnostic V/Q scans), no venous thromboembolic events were reported over a follow up period of 20 months.
●Higher rates of diagnostic V/Q scans were observed in another study of 43 pregnant patients where 70 percent were reported as normal/low probability and 11 percent as high probability [28].
●Two studies describe perfusion (Q) scanning alone for the diagnosis of PE in pregnancy [29,31]. In such studies, Q scanning alone had a negative predictive value of 100 percent [31] and only 7 percent of scans were non diagnostic [29]. Although combined V/Q scanning has not been directly compared to Q scanning alone, the advantage of Q scanning alone is that it decreases the radiation exposure to mother and fetus.
The diagnostic accuracy of V/Q scanning in the general population, a suggested diagnostic algorithm for suspected PE in pregnancy, and comparison of V/Q scanning with CTPA in pregnancy are discussed separately. (See 'Diagnostic algorithm' below and 'Comparison of V/Q scan and CTPA' below and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Ventilation perfusion scan'.)
CT pulmonary angiography — Computed tomographic pulmonary angiography (CTPA) remains a highly sensitive and specific test for the diagnosis of PE. As for nonpregnant patients, the demonstration of a filling defect in any branch of the pulmonary artery (main, lobar, segmental, subsegmental) by contrast enhancement is considered diagnostic of PE during pregnancy. Indeterminate or nondiagnostic studies are reported when the filling defect is not clearly visualized (eg, embolus in a small peripheral pulmonary artery, poor contrast flow, image interference by motion or hardware artifact). (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Diagnosis'.)
Small retrospective studies suggest that CTPA has a high negative predictive value for ruling out the diagnosis of PE in pregnancy [12,28,29,32]. However, compared to that reported in the general population, it may have a slightly higher rate of nondiagnostic studies during pregnancy, particularly when the chest radiograph is abnormal [12]. The increased blood volume and cardiac output in pregnancy make quantifying and timing the intravenous contrast bolus more difficult. Thus, in the pregnant population, CTPA is diagnostically useful when V/Q scanning is not available or is indeterminate (eg, when the chest radiograph is abnormal) or when an alternate pathology is being considered. CT technology is rapidly evolving with equipment that can provide improved imaging of the pulmonary vasculature in shorter scanning times (thereby potentially reducing radiation exposure). The diagnostic accuracy of CTPA in this context during pregnancy is presumably improved but unknown and not validated.
Four retrospective studies report variable rates of diagnostic (70 to 83 percent) and nondiagnostic (6 to 30 percent) CTPA studies in pregnant patients suspected of having PE [12,28,29,32].
●One retrospective study of 43 pregnant patients reported diagnostic findings in 81 percent (16 percent positive, 65 percent negative). The remaining 19 percent of patients had indeterminate findings [28]. Opacification was classified as good for only half of the cases but, compared to V/Q scans, interobserver agreement was better between radiologists reading CTPA (κ = 0.84; 95% CI 0.68-0.99 versus κ = 0.75; 95% CI 0.63-0.87).
●Three studies all report high rates of nondiagnostic studies (17 to 28 percent) during pregnancy [12,28,32]. For example, one retrospective study reported nondiagnostic studies in 28 and 7.5 percent of pregnant and nonpregnant patients, respectively [32]. Another retrospective study of 304 pregnant women suspected of having PE reported that, compared to the group as a whole, the rate of nondiagnostic studies was highest in the subgroup with a normal chest radiograph (17 versus 30 percent) [12].
●One retrospective study of 199 pregnant patients, of which 106 had CTPA for suspected PE, reported a high negative predictive value (99 percent) for the diagnosis of PE by CTPA [29]. Only 5.6 percent of patients had indeterminate studies, all of which were due to poor quality (poor enhancement or respiratory artifact), and none of which were found to have PE at three month follow up.
The diagnostic accuracy of CTPA in the general population, suggested diagnostic algorithm for suspected PE in pregnancy, and comparison of V/Q scanning with CTPA in pregnancy are discussed separately. (See 'Diagnostic algorithm' below and 'Comparison of V/Q scan and CTPA' below and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Computed tomography pulmonary angiography'.)
Magnetic resonance pulmonary angiography — The sensitivity and specificity of magnetic resonance pulmonary angiography (MRPA) for the diagnosis of PE during pregnancy have not been evaluated. Although no fetal teratogenicity of gadolinium has been observed in human studies, teratogenicity for high doses or prolonged exposures to gadolinium has been observed in animals [33-35]. (See "Diagnostic imaging in pregnant and nursing patients", section on 'Use of gadolinium'.)
In the general population, large clinical studies comparing MRPA with contrast-enhanced pulmonary arteriography are lacking, with sensitivities ranging from 77 to 85 percent, though higher in the lobar pulmonary arteries (100 percent) [36,37]. Gadolinium-enhanced MRPA in the general population has sensitivities and specificities ranging from 31 to 92 percent and 85 to 100 percent, respectively [36-41]. The diagnostic value of MRPA in the nonpregnant population is discussed in detail separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Magnetic resonance pulmonary angiography'.)
Contrast-enhanced pulmonary artery angiography — Contrast-enhanced pulmonary angiography (ie, digital subtraction angiography [DSA]) was the historical gold standard for the diagnosis of PE. With the emergence of CTPA and high diagnostic accuracy of V/Q scanning in pregnant patients with suspected PE, it is rarely performed in this population.
The sensitivity and specificity of contrast-enhanced pulmonary angiography for the diagnosis of PE during pregnancy have not been formally evaluated. However, a retrospective subpopulation analysis of 20 discordant cases, derived from PIOPED II, suggests that it is less sensitive than CTPA for the detection of emboli [42]. Compared to CTPA, contrast angiography had a higher number of false negative results (13 versus 2). Most of the thrombi missed on contrast angiography were subsegmental (8 cases).
This small retrospective comparison suggests that contrast-enhanced pulmonary angiography may not be as accurate as originally thought. The diagnostic value of contrast pulmonary artery angiography in the nonpregnant population is discussed in detail separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Catheter-based pulmonary angiography'.)
DIAGNOSTIC ALGORITHM — A high index of clinical suspicion and a low threshold for objective testing are critical to the successful diagnosis of suspected PE in pregnancy (algorithm 1). Clinical practice guidelines for the evaluation of suspected PE in pregnancy have been issued by the American Thoracic Society and Society of Thoracic Radiology (2011) [27], the Society of Obstetricians and Gynaecologists of Canada (2014) [43], the Royal College of Obstetricians and Gynaecologists (2015) [44], and the European Society of Cardiology and European Respiratory Society (2019) [45]. These guidelines are a useful resource for the clinician to make decisions regarding the risks and benefits of testing pregnant patients so that a diagnosis can be made promptly and therapy appropriately administered. The following sections describe our approach to the diagnosis of PE, which is largely consistent with these guidelines. An alternative approach is also described.
Pretest probability — Although pre-test probability (PTP) should be assessed, clinicians are poor at estimating the probability of PE in pregnant women and there are no validated clinical prediction guidelines for determining the PTP of PE in this population [8,13]. The difficulty in determining the pretest probability may be due to the poor performance of scoring systems for PE in pregnancy as well as the nonspecific and shared symptoms between PE and pregnancy, and low sensitivity and specificity of D-dimer in this population.
●Wells or Geneva Score – The Wells or modified Geneva scoring systems are the most common scoring system used for PE in the nonpregnant patient. Both scoring systems have limited value in the pregnant population, probably due to the high prevalence of baseline tachycardia and the low likelihood of certain risk factors (eg, malignancy or recent surgery) that are listed on the scoring system [13].
●Presenting features – As described above, the clinical manifestations of PE are variable and nonspecific. This nonspecific presentation is magnified during pregnancy due to an overlap between symptoms seen in patients with PE and those associated with the normal physiologic changes of pregnancy (eg, dyspnea occurs in up to 70 percent of normal pregnancies) [8]. Thus, identifying a PE during pregnancy is difficult and dependent upon a higher than usual index of clinical suspicion. One study evaluated the predictive value of six presenting features (chest pain, dyspnea, desaturation, tachycardia, increased alveolar-arterial gradient ≥15 mmHg, and PaO2 <65 mmHg) in 304 women with suspected PE during pregnancy or postpartum [12]. No association between any one or any combination of these features and the diagnosis of PE was found.
●D-dimer – The sensitivity and specificity of D-dimer is discussed above. (See 'Laboratory studies' above.)
Testing/imaging — The diagnosis of PE during pregnancy is challenging due to concerns regarding the exposure of mother and fetus to ionizing radiation and contrast. The evidence to support choosing one imaging modality over another is weak in the pregnant population. A choice among imaging modalities is typically based upon physician judgment, patient preference, comorbidities (eg, renal insufficiency or allergy to contrast) and potential toxicities to mother and fetus.
In general, when considering a diagnosis of PE in a pregnant patient, we suggest the following approach (algorithm 1):
●Proximal vein compression ultrasonography (CUS) should not be routinely performed as an initial test unless the clinical evaluation suggests coexistent deep venous thrombosis (DVT) (eg, leg pain, swelling, and/or erythema). If CUS is negative or not available and the clinical suspicion for PE remains, further imaging is indicated. This preference recognizes the low prevalence of DVT in pregnant patients who present with suspected PE.
●A chest radiograph is suggested in every patient who presents with respiratory symptoms concerning for PE.
●When the chest radiograph is normal, ventilation/perfusion (V/Q) scanning is preferred. V/Q scanning is sensitive and specific for the diagnosis of PE in the context of a normal radiograph. (See 'V/Q scan' above.)
●When the chest radiograph is abnormal, or when the diagnosis by V/Q scan is indeterminate, proceeding to computed tomographic pulmonary angiography (CTPA) is suggested. (See 'CT pulmonary angiography' above.)
This suggested approach places a high value on diagnostic certainty and should be tailored to the needs of each patient (algorithm 1). Modulating factors that affect modality choice, including the risks associated with radiation and contrast, are discussed below. (See 'Selection of imaging modality' below.)
An alternative approach is described below. (See 'Investigational algorithms (CTPA)' below.)
Initial CUS — The perceived benefit to considering compression ultrasonography (CUS) as an initial diagnostic test is the avoidance of radiation and contrast in the pregnant patient to obtain a diagnosis of DVT. The treatments for DVT and PE are identical such that documentation of a DVT is considered by most clinicians sufficient to terminate the diagnostic evaluation and justify immediate therapy. We reserve CUS for pregnant patients suspected of having a PE in whom the clinical evaluation suggests a coexistent DVT. If a suspicion for PE remains, a negative CUS should not reassure the clinician, nor should it obviate the need for further imaging. Signs and symptoms suggestive of a DVT are presented separately. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'Clinical presentation'.)
No direct evidence supports the use of CUS as an initial diagnostic test for the evaluation of a pregnant patient with suspected PE. The prevalence of DVT in pregnant patients suspected of having PE is unknown but estimated to be low [11]. In nonpregnant patients with suspected PE, the prevalence of DVT is 9 to 12 percent [46-49]. These data are derived from the general population that has a known DVT prevalence of 20 to 36 percent in patients with proven PE [48,49]. One study reported no cases of DVT in a subpopulation of 69 pregnant women with suspected PE that also underwent evaluation for DVT by bilateral CUS or impedance plethysmography [11].
These data suggest that the routine use of CUS as an initial diagnostic test in every pregnant patient suspected of having PE is not justified, especially when the suspicion for a DVT is low. Additionally, waiting for results of a test with unknown or low diagnostic yield potentially wastes valuable time in the workup of pregnant patients suspected of having PE.
We reserve CUS for pregnant patients suspected of having a PE in whom the clinical evaluation suggests a coexistent or symptomatic DVT. A DVT prevalence of up to 9 percent has been reported in this selected population of pregnant women (ie pregnant women clinically suspected of having both PE and DVT) [18,19]. Additionally, although not validated in large studies, the presence of two to three variables of the LEFt clinical prediction rule (left sided symptoms, edema, first trimester) was associated with DVT in 58 percent of cases [50]. Thus, in the context of suspected PE during pregnancy, it is expected that the diagnostic yield of CUS in those with symptomatic DVT is increased compared to those without a clinical suspicion for DVT. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'LEFt clinical prediction rule'.)
A negative CUS in a pregnant patient simply indicates that there is no evidence of clot in the proximal veins. Proximal vein CUS does not readily detect thrombus in the calf veins or the pelvic veins [51,52]. Additionally, proximal vein CUS may be negative in the setting of PE, because thrombus has travelled to the lungs and is no longer present in the proximal vein. In this context, if a suspicion for PE remains, a negative CUS should not reassure the clinician, nor should it obviate the need for further imaging. Preferred imaging tests to diagnose PE are discussed below. (See 'Selection of imaging modality' below.)
Chest radiograph — A normal chest radiograph increases the probability of accurate stratification of patients with V/Q scan into the known PIOPED II categories: normal/very low probability, low probability, moderate probability, or high probability [26]. An abnormal chest radiograph increases the probability of a moderate probability V/Q scan result and should prompt the clinician to avoid V/Q scan and directly proceed to CTPA. Our preference places high value on diagnostic yield in this setting and avoidance of over testing pregnant patients with suspected PE.
The additional advantage of chest radiography is the discovery of alternate pathology (pulmonary edema, cardiomegaly, pneumothorax) or findings due to pulmonary infarction that may need to be followed in patients subsequently diagnosed with PE (eg, effusion, pneumonitis).
Selection of imaging modality — The diagnosis of PE may be made based upon findings on ventilation/perfusion (V/Q) scanning or computed tomographic pulmonary angiography (CTPA). The choice of imaging modality (V/Q scan versus CTPA) in pregnant women is challenging. The risks and benefits of each modality need to be weighed separately in the context of patient preference, diagnostic accuracy, availability, and amounts of radiation and contrast exposure. Occasionally, more than one test will be necessary to definitively diagnose PE.
The data to support choosing one modality over the other are conflicting. On balance, we suggest that V/Q is the preferred test in pregnant women with suspected PE when the chest radiograph is normal [12,32,53-55]. However, most clinicians, including us, use CTPA as their primary modality for evaluating pregnant females for PE based upon the practical rationale that CTPA is more readily available than V/Q scanning, may provide an alternate diagnosis, and is associated with lower doses of radiation than in the past. CTPA is also the preferred modality when the chest radiograph is abnormal, the diagnosis is in doubt by V/Q scan (eg, indeterminate/moderate probability V/Q scan), V/Q scanning is not available, and/or an alternate diagnosis is in question [27,56,57]. In support of this practice, one single-center retrospective study of 157 pregnant females reported that CTPA was used more commonly than V/Q scanning to diagnose PE in the first trimester (56 percent versus 21 percent), second trimester (58 versus 17 percent), and third trimester (70 versus 18 percent) [58].
Additional modalities (eg, magnetic resonance or contrast pulmonary angiography) are rarely performed and poorly validated in pregnancy, but can be considered on a case-by-case basis. Traditionally, D-dimer has generally been considered to have little value in the diagnostic evaluation of suspected PE in pregnancy, although a study investigating an algorithm in pregnancy that includes D-dimer has shown promising results. (See 'Investigational algorithms (CTPA)' below.)
Discussed below are comparative diagnostic studies and modulating factors (eg, radiation and contrast risk), to help guide the clinician in the selection of one imaging modality for the diagnosis of PE in pregnancy. The diagnostic accuracy of each modality is discussed separately. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'Imaging'.)
Comparison of V/Q scan and CTPA — Only retrospective studies with mixed results are available for the comparison of ventilation/perfusion (V/Q) scanning and computed tomographic pulmonary angiography (CTPA) in the pregnant population.
Two initial studies suggest that CTPA is inferior to V/Q scanning:
●One retrospective cohort study of 304 women (pregnant or within six weeks postpartum) with a clinical suspicion of PE reported that, among women with a normal chest radiograph, CTPA was more often nondiagnostic than V/Q scanning (30 versus 5.6 percent; adjusted odds ratio 5.4; 95% CI 1.4-20.1) [12].
●Another study of 53 pregnant patients reported that, compared to V/Q scanning, CTPA had a higher rate of inadequate/nondiagnostic scans (4 versus 36 percent, respectively) [53]. Additionally, CTPA had a significantly higher diagnostic inadequacy rate among pregnant compared with nonpregnant women with suspected PE (36 versus 2 percent). Transient interruption of contrast material by unopacified blood from the inferior vena cava was identified in 8 of 10 nondiagnostic pulmonary CTPA studies.
Two subsequent studies suggest comparable diagnostic accuracy between V/Q scanning and CTPA [28,29]:
●In a retrospective analysis of images from 46 CTPA examinations and 91 V/Q examinations in pregnant women, the two techniques had a comparable performance for the diagnosis of PE during pregnancy [28]. Compared with CTPA, V/Q scanning had similar rates of positive (16 versus 11 percent), negative (65 versus 70 percent), and indeterminate findings (19 versus 19 percent). Additionally, interobserver agreement was better for CTPA, and also enabled alternative diagnosis of unsuspected disease in 12 percent of cases (eg, pneumonia).
●Another retrospective study of 199 pregnant patients reported negative predictive values of 99 and 100 percent for CTPA and perfusion (Q) scanning alone, respectively, for the diagnosis of PE [29]. In this study only 6 percent of CTPA images were deemed inadequate and 13 percent showed an alternative diagnosis.
A review of 11 retrospective studies (including those cited above) reported a lower median sensitivity for CTPA than lung scintigraphy (83 and 100) percent while the negative predictive value was 100 percent for both imaging modalities [59]. CTPA also had a slightly higher rate of inconclusive results (6 versus 4 percent). However, given the limitations including a lack of reference standard for diagnosis, small and retrospective nature of studies, and the potential for false positive results with scintigraphy, the evidence was insufficient to determine which test was more sensitive.
Though unproven, the discrepancy in the diagnostic accuracy of CTPA between pregnant and nonpregnant patients has been ascribed to interrupted flow from the inferior vena cava or altered flow of contrast material due to high plasma volume in pregnancy [32,53-55]. However, CTPA has specific advantages and disadvantages for the diagnosis of PE that apply to both pregnant and nonpregnant populations. For example, CTPA may be more readily available in some institutions during off-duty hours. In addition, it has been shown to identify alternate pathologies in 12 to 13 percent of cases [28,29]. However, coexistent renal insufficiency, contrast allergies, or weight limitations of the CT table may limit its use in individual patients.
The interpretation of V/Q scans in the pregnant and nonpregnant population is discussed separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Hemodynamically stable patients'.)
Radiation and contrast exposure — The decision to select an imaging modality for the diagnosis of PE in pregnancy should be made in the context of potential fetal teratogenicity and radiation risk to both mother and fetus. In general, the risk of radiation (from V/Q scanning and CTPA) and iodinated contrast is considered low and must be weighed against the 20 to 30 percent risk of maternal mortality of untreated PE. In animal studies, gadolinium is teratogenic in high doses.
Radiation — The International Commission of Radiologic Protection suggests that the radiation doses delivered in utero by imaging tests (such as those performed in the diagnosis of PE) present no measurable increased risk of fetal death or developmental abnormalities over the background incidence of these entities [60]. The National Council of Radiation Protection and Measurements considers the risk of radiation-associated abnormalities with exposure to less than 50 mGy when compared with other risks of pregnancy [61]. (See "Diagnostic imaging in pregnant and nursing patients".)
Similar to nonpregnant patients, low-level ionizing radiation assumes some cumulative risk for carcinogenesis, measured over a life-time. In general, it is considered that the mother assumes a greater carcinogenic risk (particularly, for lung and breast cancer) than the fetus. However, a few studies have suggested a possible small increase in the risk of childhood leukemia from 1 in 2800 (baseline risk) to 1 in 2000 among children exposed to low dose ionizing radiation in utero [62-65].
Reported amounts of radiation exposure are variable for imaging modalities utilized in the diagnosis of PE (table 2). The wide range is influenced by gestational age and also reflects heterogeneity in protocols and equipment used by different institutions. Studies that have measured radiation exposure to fetus and mother from imaging modalities used for the evaluation of suspected PE estimate the following:
●CTPA delivers slightly lower fetal radiation doses than V/Q scanning (0.003 to 0.131 mGy versus 0.32 to 0.74 mGy, in the first through third trimester) [66].
●CTPA delivers higher maternal doses of radiation than V/Q scanning (7.3 versus 0.9 mSv) [28].
●V/Q scanning results in substantially (150-fold) lower breast and lung irradiation than CTPA [67].
●The combination of a chest radiograph, V/Q scanning, and pulmonary arteriography has an estimated fetal radiation exposure less than 0.5 mSv [8,68,69]. This is 100 to 200 times less than the dose thought to produce a significant risk of fetal anomalies.
●The exposure during contrast pulmonary angiography is dependent upon the method of administration of contrast (internal jugular, brachial or femoral vein) and length of procedure
The following measures can reduce fetal radiation exposure from V/Q scanning but have not been validated diagnostically: reducing the dose of the perfusion agent in patients who can tolerate the longer imaging times required for quality scans; performing perfusion (Q) scanning first without proceeding to ventilation scanning (V) when Q scan images are normal; and good hydration with frequent voiding to minimize radiation due to pooling of radionuclide in the maternal bladder.
Contrast — Iodinated and gadolinium contrast agents, when administered intravenously, cross the placenta to enter the amniotic fluid and the fetal circulation [62].
The major concern regarding the administration of iodinated contrast is the effect on thyroid function. A retrospective study of 344 pregnant women who underwent contrast-enhanced CT pulmonary angiography for suspected PE found no abnormal levels of thyroxine in neonates at birth [70]. This study suggests that the risk of neonatal hypothyroidism, due to fetal exposure to free iodine, is very low. No animal studies have shown teratogenicity for iodinated contrast [34].
No fetal teratogenicity of gadolinium has been observed in human studies. However, teratogenicity for high doses or prolonged exposures to gadolinium has been observed in animals [34,35]. (See 'Magnetic resonance pulmonary angiography' above.)
Practical considerations — A delay in diagnosis of venous thromboembolism is associated with a poor outcome and higher mortality [71]. Staffing burdens for specific tests (eg, V/Q scanning and vascular studies of the lower extremities) may impede the clinician's ability to make a timely diagnosis. For example, in many institutions, CTPA is more readily available than V/Q scanning. In addition, it appears that interobserver agreement is better for radiologists reading CT than nuclear scans [28].
In support of this concept, a 1998 survey of 1000 clinician-directors of nuclear medicine facilities found that only 67 percent of respondents reported that they perform V/Q scans in pregnant women [69]. The reasons for this are unclear but may be due to limited nuclear medicine staff in some institutions to perform and interpret scans, especially during off duty hours. Under such circumstances, when the clinical suspicion is high for VTE, perceived roadblocks should not delay therapy while the clinician seeks an alternative modality for a timely diagnosis.
Clot resolution has not been studied in pregnancy. However, in patients who have clinical symptoms days to weeks prior to coming to medical attention, a delayed presentation should not deter the clinician from using the same approach (algorithm 1). Clot resolution in nonpregnant patients is discussed separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Clinical presentation'.)
In patients where there is a high clinical suspicion for PE, particularly if the diagnostic evaluation cannot be completed rapidly, we recommend immediately administering a dose of low molecular weight heparin [45]. The results of the diagnostic evaluation will then determine whether PE is confirmed and whether anticoagulation should be continued.
INVESTIGATIONAL ALGORITHMS (CTPA) — While pretest probability (PTP) and D-dimer testing followed by computed tomographic pulmonary angiography (CTPA) are not traditionally part of the investigations used to diagnose pulmonary embolus (PE) in pregnant women, two large prospective trials have examined the value of algorithms similar to those used in the general population:
●Results of a prospective trial suggested that a protocolized approach to diagnosis that involves PTP assessment using the revised Geneva score (calculator 1), high sensitivity D-dimer testing, bilateral lower limb compression ultrasonography (CUS), and CTPA may be an appropriate alternative [72]. In this multicenter trial, 395 pregnant women with suspected PE underwent evaluation [72]. PE was ruled out with a low or intermediate clinical PTP and a negative D-dimer. All patients with a high PTP or positive D-dimer underwent bilateral CUS; if CUS was negative, the patient underwent CTPA. Ventilation/perfusion (V/Q) scanning was performed if CTPA was inconclusive. Patients with a positive CUS, CTPA, or high probability V/Q scan were diagnosed with PE, while PE was considered excluded in those with a negative work up. PE was diagnosed in 7.1 percent. At three months, among those with a negative workup, no patient developed symptomatic venous thromboembolism. However, there were several protocol deviations (10 percent), indicating the difficulty of adherence to protocols like this in this population. Further limiting the value of this protocol is that the proportion of women with a negative D-dimer decreased with gestational age, supporting the known limited utility of D-dimer during pregnancy (25 percent during the first trimester, 11 percent during the second trimester, and 4 percent during the third trimester had a normal D-dimer). In addition, 6 percent of women in whom PE was excluded received either prophylactic or therapeutic anticoagulation, which may have biased the results in favor of using this protocol. Further validation studies are required before a protocolized CTPA-guided approach like this can be routinely used in pregnant women suspected as having PE.
●Another prospective study assessed the value of the YEARS criteria adapted for pregnant women for the diagnosis of PE [73]. In non-pregnant patients, the YEARS criteria have been shown to reduce the number of unnecessary CT scans performed during the evaluation of those with suspected PE, the details of which are discussed separately (see "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'D-dimer'). In this study, 498 pregnant women with suspected PE were evaluated using the three YEARS criteria (clinical signs of DVT, hemoptysis, and PE as the most likely diagnosis). PE was excluded in patients with zero YEARS items and a D-dimer level <1000 ng/mL, and patients with ≥1 YEARS items and a D-dimer <500 ng/mL. Patients with clinical signs of DVT underwent compression ultrasonography and were treated if it was positive but did not undergo CTPA, which was the adaptation made in the algorithm for pregnant women. All other patients underwent CTPA; PE was diagnosed in those with a positive CTPA (4 percent). During the three month follow-up, DVT was diagnosed in one patient (0.21 percent) and no patient had a PE. A subgroup analysis determined that the efficiency was greatest during the first trimester, when CTPA was avoided in 65 percent of patients compared with 32 percent in the third trimester. Similar to the study above, there were several protocol violations (11 percent), and the value of the D-dimer and the protocol decreased with gestational age. In addition, the population studied only included those with a high suspicion for PE rather than a mix of patients with low, moderate, and high suspicion, which may have biased the results in favor of the algorithm.
Further validation studies are required before protocolized approaches like these can be routinely used in pregnant women suspected as having PE.
DIAGNOSIS OF PE — A definitive diagnosis of PE, in the pregnant patient is made by the demonstration of a high probability ventilation perfusion (V/Q) scan or visualization of clot by computed tomographic pulmonary angiogram (CTPA), magnetic resonance, or contrast angiography. Definitive diagnosis dictates immediate anticoagulation where the benefits in mortality outweigh the risks of bleeding.
Occasionally, a clinically confident diagnosis can be made in patients with indeterminate imaging studies (eg, moderate probability V/Q scan) in the context of high clinical suspicion. In this situation, physician judgment and patient preference for anticoagulation should be strongly considered in the context of the high maternal mortality for an untreated PE and weighed against the risks of further testing and the risk of bleeding.
Rarely, PE is diagnosed on imaging (contrast-enhanced CT) done for an alternate reason or discovered pathologically in a resected pulmonary lobe.
DIFFERENTIAL DIAGNOSIS OF PE — The differential diagnosis of PE in pregnant patients includes other entities with a variety of presenting features ranging from mild dyspnea to shock. The major competing diagnoses, apart from the condition of pregnancy, are heart failure, pneumothorax, and pneumonia. Hypoxemia is unusual but should always alert the clinical to a potentially serious underlying pathology. PE can coexist with other conditions such that the finding of an alternate diagnosis should lower the clinical suspicion but does not always obviate the need for diagnostic imaging.
The differential diagnosis of the presenting signs and symptoms, dyspnea, chest pain, hemoptysis, pleural effusion, and hypoxemia, is discussed separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Differential diagnosis' and "Clinical manifestations and diagnosis of early pregnancy", section on 'Dyspnea'.)
The differential diagnosis of common conditions that mimic PE include the following:
●Pregnancy – Distinguishing pregnancy-related symptoms from PE is challenging. Many of the most common signs and symptoms of PE (dyspnea, tachycardia and tachypnea) are associated with a normal pregnancy. For example dyspnea occurs at some point in up to 70 percent of normal pregnancies, often stabilizing near term [8,9,74,75].
The acute development of symptoms (eg, dyspnea, chest pain) may favor a diagnosis of acute PE rather than pregnancy-related symptoms. However, progressive dyspnea may be seen with chronic venous thromboembolism or with the development of a small embolus in a patient with pre-existing lung disease. (See "Maternal adaptations to pregnancy: Dyspnea and other physiologic respiratory changes" and "Clinical manifestations and diagnosis of early pregnancy", section on 'Dyspnea' and "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes".)
●Peripartum cardiomyopathy – Dyspnea, tachycardia, and lower extremity swelling during pregnancy can be normal, due to PE, or related to heart failure. Heart failure is a clinically important diagnosis that needs to be distinguished from PE as it can also impact survival and warrants different therapy. Heart failure due to preexisting (known or unknown) or newly developed peripartum cardiomyopathy is associated with more slowly progressive dyspnea and orthopnea. An echocardiogram will distinguish heart failure from PE. The signs and symptoms of peripartum cardiomyopathy are discussed separately. (See "Peripartum cardiomyopathy: Etiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)
●Other – Other conditions that may mimic PE during pregnancy include pneumothorax, vasculitis, and pneumonia, which are discussed separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Differential diagnosis'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Pulmonary embolism (blood clot in the lungs) (The Basics)")
●Beyond the Basics topics (see "Patient education: Pulmonary embolism (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Pulmonary embolism (PE) has a wide variety of presenting features, ranging from no symptoms to shock or sudden death. This nonspecific presentation poses challenges during pregnancy due to an overlap with symptoms due to the normal physiologic changes of pregnancy. PE should be suspected in patients with any one or combination of the following symptoms: acute-onset dyspnea, pleuritic pain, and hemoptysis. (See 'Clinical presentation' above.)
●Clinicians are notoriously poor at estimating the probability of PE in pregnant women, and there are no validated clinical prediction guidelines or pretest probability tools for determining the probability of PE in this population. (See 'Pretest probability' above.)
●All patients with suspected PE should have a chest radiograph, which both provides information about alternative diagnoses and impacts the choice of further diagnostic testing. (See 'Chest radiograph' above and 'Chest radiograph' above.)
●Our suggested approach for further evaluation of the patient with suspected PE prioritizes an accurate and rapid diagnosis (algorithm 1). Preference for use of one imaging modality over another is typically based upon physician judgment, patient preference, comorbidities (eg, renal insufficiency or allergy to contrast) and potential toxicities to mother and fetus. (See 'Diagnostic algorithm' above.)
•For pregnant patients with suspected PE in whom clinical evaluation suggests a coexistent deep venous thrombosis (DVT), we suggest that proximal vein compression ultrasonography (CUS) be performed. For patients in whom the CUS is negative, not available, or those in whom a coexistent DVT is not suspected, we suggest lung imaging with ventilation perfusion (V/Q) or computed tomographic pulmonary angiogram (CTPA). (See 'Initial CUS' above.)
•For pregnant patients with suspected PE in whom the chest radiograph is normal, we suggest V/Q scan, provided it is available. (See 'V/Q scan' above and 'Selection of imaging modality' above.)
•If V/Q scan is not available, is indeterminate, the chest radiograph is abnormal, or another diagnosis is suspected, we suggest CTPA rather than V/Q scan. (See 'CT pulmonary angiography' above and 'Selection of imaging modality' above.)
•In general, the risk of radiation (from V/Q scanning and CTPA) and iodinated contrast is considered low. However, in animal studies, gadolinium is teratogenic in high doses, while fetal teratogenicity is humans is unknown. (See 'Radiation and contrast exposure' above.)
●A definitive diagnosis of PE is made by the demonstration of a high probability V/Q scan or visualization of clot by CTPA. Magnetic resonance and contrast angiography are rarely used in pregnant patients. CUS is not definitively diagnostic of PE but can be used to confirm DVT and thus avoid lung imaging for those in whom both DVT and PE are suspected. (See 'Diagnosis of PE' above.)
●The differential diagnosis of PE in pregnant patients depends upon the presenting signs and symptoms. The major competing diagnoses, apart from the condition of pregnancy, are heart failure, pneumothorax, and pneumonia. Hypoxemia is unusual but should always alert the clinical to serious underlying pathology. PE can coexist with other conditions such that the finding of an alternate diagnosis should lower the clinical suspicion but does not always obviate the need for diagnostic imaging. (See 'Differential diagnosis of PE' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David R Schwartz, MD, who contributed to an earlier version of this topic review.
