Pulmonary embolism in pregnancy: Epidemiology, pathogenesis, and diagnosis
- David R Schwartz, MD
David R Schwartz, MD
- Associate Professor of Clinical Medicine
- Section Chief, Critical Care
- NYU Medical Center
- Atul Malhotra, MD
Atul Malhotra, MD
- Kenneth M Moser Professor, Department of Medicine
- University of California, San Diego
- Steven E Weinberger, MD
Steven E Weinberger, MD
- Adjunct Professor of Medicine
- University of Pennsylvania School of Medicine
- Executive Vice President and CEO Emeritus
- American College of Physicians
- Section Editors
- Lawrence LK Leung, MD
Lawrence LK Leung, MD
- Editor-in-Chief — Hematology
- Section Editor — Disorders of Hemostasis and Coagulation
- Professor of Medicine
- Stanford University School of Medicine
- Jess Mandel, MD
Jess Mandel, MD
- Section Editor — Pulmonary Vascular Disease
- Professor of Medicine
- University of California, San Diego
- Charles J Lockwood, MD, MHCM
Charles J Lockwood, MD, MHCM
- Section Editor — Obstetrics
- Senior Vice President, USF Health
- Dean, Morsani College of Medicine
- Professor, Obstetrics and Gynecology
- University of South Florida
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".)
The epidemiology of VTE during pregnancy and the puerperium is discussed separately. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'Epidemiology'.)
Factors that increase the risk of VTE during pregnancy and the puerperium are discussed separately. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'Compressive ultrasound and subsequent testing'.)
- Marik PE, Plante LA. Venous thromboembolic disease and pregnancy. N Engl J Med 2008; 359:2025.
- Morris JM, Algert CS, Roberts CL. Incidence and risk factors for pulmonary embolism in the postpartum period. J Thromb Haemost 2010; 8:998.
- James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol 2006; 194:1311.
- Chang J, Elam-Evans LD, Berg CJ, et al. Pregnancy-related mortality surveillance--United States, 1991--1999. MMWR Surveill Summ 2003; 52:1.
- The National Institute for Clinical Excellence. Why mothers die 2000–2002 — report on confidential enquiries into maternal deaths in the United Kingdom. London: Royal College of Obstetricians and Gynaecologists Press, 2003.
- The Confidential Enquiry into Maternal and Child Health (CEMACH). Saving mothers’ lives: reviewing maternal deaths to make motherhood safer — 2003–2005: the seventh report on confidential enquiries into maternal deaths in the United Kingdom. London: CEMACH, 2007.
- MacKAy AP, Berg CJ, Liu X, et al. Changes in pregnancy mortality ascertainment: United States, 1999-2005. Obstet Gynecol 2011; 118:104.
- PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 1990; 263:2753.
- Gherman RB, Goodwin TM, Leung B, et al. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstet Gynecol 1999; 94:730.
- Chan WS, Ray JG, Murray S, et al. Suspected pulmonary embolism in pregnancy: clinical presentation, results of lung scanning, and subsequent maternal and pediatric outcomes. Arch Intern Med 2002; 162:1170.
- Cahill AG, Stout MJ, Macones GA, Bhalla S. Diagnosing pulmonary embolism in pregnancy using computed-tomographic angiography or ventilation-perfusion. Obstet Gynecol 2009; 114:124.
- Stein PD, Goldhaber SZ, Henry JW. Alveolar-arterial oxygen gradient in the assessment of acute pulmonary embolism. Chest 1995; 107:139.
- Stein PD, Goldhaber SZ, Henry JW, Miller AC. Arterial blood gas analysis in the assessment of suspected acute pulmonary embolism. Chest 1996; 109:78.
- Powrie RO, Larson L, Rosene-Montella K, et al. Alveolar-arterial oxygen gradient in acute pulmonary embolism in pregnancy. Am J Obstet Gynecol 1998; 178:394.
- Kline JA, Williams GW, Hernandez-Nino J. D-dimer concentrations in normal pregnancy: new diagnostic thresholds are needed. Clin Chem 2005; 51:825.
- Chan WS, Chunilal S, Lee A, et al. A red blood cell agglutination D-dimer test to exclude deep venous thrombosis in pregnancy. Ann Intern Med 2007; 147:165.
- Chan WS, Lee A, Spencer FA, et al. D-dimer testing in pregnant patients: towards determining the next 'level' in the diagnosis of deep vein thrombosis. J Thromb Haemost 2010; 8:1004.
- Kovac M, Mikovic Z, Rakicevic L, et al. The use of D-dimer with new cutoff can be useful in diagnosis of venous thromboembolism in pregnancy. Eur J Obstet Gynecol Reprod Biol 2010; 148:27.
- Damodaram M, Kaladindi M, Luckit J, Yoong W. D-dimers as a screening test for venous thromboembolism in pregnancy: is it of any use? J Obstet Gynaecol 2009; 29:101.
- Levy MS, Spencer F, Ginsberg JS, Anderson JA. Reading between the (Guidelines). Management of submassive pulmonary embolism in the first trimester of pregnancy. Thromb Res 2008; 121:705.
- To MS, Hunt BJ, Nelson-Piercy C. A negative D-dimer does not exclude venous thromboembolism (VTE) in pregnancy. J Obstet Gynaecol 2008; 28:222.
- Worsley DF, Alavi A, Aronchick JM, et al. Chest radiographic findings in patients with acute pulmonary embolism: observations from the PIOPED Study. Radiology 1993; 189:133.
- Greenspan RH, Ravin CE, Polansky SM, McLoud TC. Accuracy of the chest radiograph in diagnosis of pulmonary embolism. Invest Radiol 1982; 17:539.
- Gottschalk A, Stein PD, Goodman LR, Sostman HD. Overview of Prospective Investigation of Pulmonary Embolism Diagnosis II. Semin Nucl Med 2002; 32:173.
- Leung AN, Bull TM, Jaeschke R, et al. An official American Thoracic Society/Society of Thoracic Radiology clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy. Am J Respir Crit Care Med 2011; 184:1200.
- Revel MP, Cohen S, Sanchez O, et al. Pulmonary embolism during pregnancy: diagnosis with lung scintigraphy or CT angiography? Radiology 2011; 258:590.
- Shahir K, Goodman LR, Tali A, et al. Pulmonary embolism in pregnancy: CT pulmonary angiography versus perfusion scanning. AJR Am J Roentgenol 2010; 195:W214.
- Balan KK, Critchley M, Vedavathy KK, et al. The value of ventilation-perfusion imaging in pregnancy. Br J Radiol 1997; 70:338.
- Scarsbrook AF, Bradley KM, Gleeson FV. Perfusion scintigraphy: diagnostic utility in pregnant women with suspected pulmonary embolic disease. Eur Radiol 2007; 17:2554.
- U-King-Im JM, Freeman SJ, Boylan T, Cheow HK. Quality of CT pulmonary angiography for suspected pulmonary embolus in pregnancy. Eur Radiol 2008; 18:2709.
- Stein PD, Chenevert TL, Fowler SE, et al. Gadolinium-enhanced magnetic resonance angiography for pulmonary embolism: a multicenter prospective study (PIOPED III). Ann Intern Med 2010; 152:434.
- Food and Drug Administration. Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling. Fed Regist 2008;29:30831– 30868.
- Lin SP, Brown JJ. MR contrast agents: physical and pharmacologic basics. J Magn Reson Imaging 2007; 25:884.
- Meaney JF, Weg JG, Chenevert TL, et al. Diagnosis of pulmonary embolism with magnetic resonance angiography. N Engl J Med 1997; 336:1422.
- Oudkerk M, van Beek EJ, Wielopolski P, et al. Comparison of contrast-enhanced magnetic resonance angiography and conventional pulmonary angiography for the diagnosis of pulmonary embolism: a prospective study. Lancet 2002; 359:1643.
- Kluge A, Luboldt W, Bachmann G. Acute pulmonary embolism to the subsegmental level: diagnostic accuracy of three MRI techniques compared with 16-MDCT. AJR Am J Roentgenol 2006; 187:W7.
- Gupta A, Frazer CK, Ferguson JM, et al. Acute pulmonary embolism: diagnosis with MR angiography. Radiology 1999; 210:353.
- Ohno Y, Higashino T, Takenaka D, et al. MR angiography with sensitivity encoding (SENSE) for suspected pulmonary embolism: comparison with MDCT and ventilation-perfusion scintigraphy. AJR Am J Roentgenol 2004; 183:91.
- Pleszewski B, Chartrand-Lefebvre C, Qanadli SD, et al. Gadolinium-enhanced pulmonary magnetic resonance angiography in the diagnosis of acute pulmonary embolism: a prospective study on 48 patients. Clin Imaging 2006; 30:166.
- Wittram C, Waltman AC, Shepard JA, et al. Discordance between CT and angiography in the PIOPED II study. Radiology 2007; 244:883.
- Stein PD, Hull RD, Saltzman HA, Pineo G. Strategy for diagnosis of patients with suspected acute pulmonary embolism. Chest 1993; 103:1553.
- Turkstra F, Kuijer PM, van Beek EJ, et al. Diagnostic utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism. Ann Intern Med 1997; 126:775.
- Righini M, Le Gal G, Aujesky D, et al. Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial. Lancet 2008; 371:1343.
- van Rossum AB, van Houwelingen HC, Kieft GJ, Pattynama PM. Prevalence of deep vein thrombosis in suspected and proven pulmonary embolism: a meta-analysis. Br J Radiol 1998; 71:1260.
- Carpenter JP, Holland GA, Baum RA, et al. Magnetic resonance venography for the detection of deep venous thrombosis: comparison with contrast venography and duplex Doppler ultrasonography. J Vasc Surg 1993; 18:734.
- Kearon C, Ginsberg JS, Hirsh J. The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Ann Intern Med 1998; 129:1044.
- Macklon NS, Greer IA, Bowman AW. An ultrasound study of gestational and postural changes in the deep venous system of the leg in pregnancy. Br J Obstet Gynaecol 1997; 104:191.
- Ridge CA, McDermott S, Freyne BJ, et al. Pulmonary embolism in pregnancy: comparison of pulmonary CT angiography and lung scintigraphy. AJR Am J Roentgenol 2009; 193:1223.
- Andreou AK, Curtin JJ, Wilde S, Clark A. Does pregnancy affect vascular enhancement in patients undergoing CT pulmonary angiography? Eur Radiol 2008; 18:2716.
- Litmanovich D, Boiselle PM, Bankier AA, et al. Dose reduction in computed tomographic angiography of pregnant patients with suspected acute pulmonary embolism. J Comput Assist Tomogr 2009; 33:961.
- Arya R. How I manage venous thromboembolism in pregnancy. Br J Haematol 2011; 153:698.
- Leung AN, Bull TM, Jaeschke R, et al. American Thoracic Society documents: an official American Thoracic Society/Society of Thoracic Radiology Clinical Practice Guideline--Evaluation of Suspected Pulmonary Embolism in Pregnancy. Radiology 2012; 262:635.
- van Mens TE, Scheres LJ, de Jong PG, et al. Imaging for the exclusion of pulmonary embolism in pregnancy. Cochrane Database Syst Rev 2017; 1:CD011053.
- International Commission of Radiological Protection. Pregnancy and medical radiation: Publication 84. Ann ICRP 2000;30:1–44.
- McCollough CH, Schueler BA, Atwell TD, Braun NN, Regner DM, Brown DL, LeRoy AJ. Radiation exposure and pregnancy: when should we be concerned? Radiographics 2007;27:909–917; discussion 917–908.
- Chen MM, Coakley FV, Kaimal A, Laros RK Jr. Guidelines for computed tomography and magnetic resonance imaging use during pregnancy and lactation. Obstet Gynecol 2008; 112:333.
- Harvey EB, Boice JD Jr, Honeyman M, Flannery JT. Prenatal x-ray exposure and childhood cancer in twins. N Engl J Med 1985; 312:541.
- Brent RL. The effects of embryonic and fetal exposure to x-ray, microwaves, and ultrasound. Clin Perinatol 1986; 13:615.
- Mole RH. Childhood cancer after prenatal exposure to diagnostic X-ray examinations in Britain. Br J Cancer 1990; 62:152.
- Winer-Muram HT, Boone JM, Brown HL, et al. Pulmonary embolism in pregnant patients: fetal radiation dose with helical CT. Radiology 2002; 224:487.
- Bourjeily G, Paidas M, Khalil H, et al. Pulmonary embolism in pregnancy. Lancet 2010; 375:500.
- Guidelines on diagnosis and management of acute pulmonary embolism. Task Force on Pulmonary Embolism, European Society of Cardiology. Eur Heart J 2000; 21:1301.
- Boiselle PM, Reddy SS, Villas PA, et al. Pulmonary embolus in pregnant patients: survey of ventilation-perfusion imaging policies and practices. Radiology 1998; 207:201.
- Bourjeily G, Chalhoub M, Phornphutkul C, et al. Neonatal thyroid function: effect of a single exposure to iodinated contrast medium in utero. Radiology 2010; 256:744.
- Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353:1386.
- Goldhaber SZ. Pulmonary embolism. N Engl J Med 1998; 339:93.
- Weinberger SE, Weiss ST, Cohen WR, et al. Pregnancy and the lung. Am Rev Respir Dis 1980; 121:559.
- RISK FACTORS
- CLINICAL PRESENTATION
- LABORATORY STUDIES
- Chest radiograph
- V/Q scan
- CT pulmonary angiography
- Magnetic resonance pulmonary angiography
- Contrast-enhanced pulmonary artery angiography
- DIAGNOSTIC ALGORITHM
- Pretest probability
- - Initial CUS
- - Chest radiograph
- - Selection of imaging modality
- Comparison of V/Q and CTPA
- Radiation and contrast exposure
- - Radiation
- - Contrast
- Practical considerations
- DIAGNOSIS OF PE
- DIFFERENTIAL DIAGNOSIS OF PE
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS