Diagnosis of Pulmonary Embolism in Pregnancy

Jack Fitzsimmons; Laura Hart; Emily Oliver; Wadia Mulla

doi:10.1055/a-2112-8049

American Journal of Perinatology, Table of Contents

Am J Perinatol 2024; 41(S 01): e2307-e2312
DOI: 10.1055/a-2112-8049

Clinical Opinion

Diagnosis of Pulmonary Embolism in Pregnancy

Jack Fitzsimmons

¹Department of Obstetrics, Gynecology and Reproductive Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania

,

Laura Hart

¹Department of Obstetrics, Gynecology and Reproductive Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania

,

Emily Oliver

¹Department of Obstetrics, Gynecology and Reproductive Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania

,

Wadia Mulla

²Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania

› Author Affiliations

Abstract

Pulmonary embolism (PE) is a significant cause of obstetric morbidity and mortality. However, overdiagnosis related to excessive use of diagnostic testing is also associated with long-term major health issues, including impact on future pregnancies and subsequent health care. Accurate diagnosis of PE depends on the knowledge of prevalence of PE in the pregnant population, the a priori probability of a PE based on specific findings in a given patient, and understanding of the accuracy of computed tomography pulmonary angiography (CTPA), the dominant diagnostic modality employed for this diagnosis. Venous thromboembolism is widely considered to be more common in pregnancy. However, this term includes both deep venous thrombosis as well as PE. While the former appears to be more common, published data on the prevalence of PE in pregnancy show little or no increase relative to the general population. Given the published data on the sensitivity and specificity of CTPA, a positive reading is more likely to be a false positive unless the probability of a PE in a given patient is at least 5% (a 200-fold increase from baseline). Doubling the probability to 10% (a 400-fold increase) only improves the positive predictive value to approximately 67%. Strategies to refine the a priori probability of a PE in a given patient are detailed, including scoring systems and D-dimer measurements. A careful history and physical examination and thoughtful development of a differential diagnosis are key elements of clinical practice and should include both the likelihood of each possible diagnosis and the accuracy of diagnostic modalities. This approach should precede the application of a given algorithm. Such a structured approach can decrease utilization and limit false positive diagnoses without increasing morbidity or mortality.

Key Points

Incidence of PE is lower than assumed.
Incidence is critical for assessing predictive value of a test.
Computed tomography angiography is likely overused in pregnancy.
Clinical scoring and D-dimer have a role in PE diagnosis.

Keywords

pulmonary embolism - venous thromboembolism - computed tomography pulmonary angiography

Full Text

References

References
1 Greenberg J, Green JB. Over-testing: why more is not better. Am J Med 2014; 127 (05) 362-363
2 Kline JA, Garrett JS, Sarmiento EJ, Strachan CC, Courtney DM. Over-testing for suspected pulmonary embolism in American emergency departments: the continuing epidemic. Circ Cardiovasc Qual Outcomes 2020; 13 (01) e005753
3 Thurlow LE, Van Dam PJ, Prior SJ, Tran V. Use of computed tomography pulmonary angiography in emergency departments: a literature review. Healthcare (Basel) 2022; 10 (05) 753
4 Newman DH, Schriger DL. Rethinking testing for pulmonary embolism: less is more. Ann Emerg Med 2011; 57 (06) 622-627.e3
5 Osman M, Subedi SK, Ahmed A. et al. Computed tomography pulmonary angiography is overused to diagnose pulmonary embolism in the emergency department of academic community hospital. J Community Hosp Intern Med Perspect 2018; 8 (01) 6-10
6 Perelas A, Dimou A, Saenz A. et al. CT pulmonary angiography utilization in the emergency department: diagnostic yield and adherence to current guidelines. Am J Med Qual 2015; 30 (06) 571-577
7 Levin D, Seo JB, Kiely DG. et al; 2013 International Workshop for Pulmonary Functional Imaging (IWPFI). Triage for suspected acute pulmonary embolism: think before opening Pandora's Box. Eur J Radiol 2015; 84 (06) 1202-1211
8 Stein PD, Fowler SE, Goodman LR. et al; PIOPED II Investigators. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med 2006; 354 (22) 2317-2327
9 Cronin P, Dwamena BA. A clinically meaningful interpretation of the prospective investigation of pulmonary embolism diagnosis (PIOPED) II and III data. Acad Radiol 2018; 25 (05) 561-572
10 Weitz JI, Ginsberg JS. Venous thrombosis and embolism. In: Goldman L, Schafer AI. eds. Goldman-Cecil Medicine. 26th ed. Philadelphia, PA: Elsevier; 2020: 478-480
11 Hogan S, Greene J, Flemming J. Rate of non-diagnostic computerized tomography pulmonary angiograms (CTPAs) performed for diagnosis of pulmonary embolism in pregnant and immediately postpartum patients. Obstet Gynecol Int 2019; 2019: 1432759
12 Ingelfinger JA, Mosteller F, Thibodeau LA, Ware JH. Biostatistics in Clinical Medicine. New York, NY: Macmillan Publishing Company; 1983: 9-15
13 Thromboembolic Disorders. . In: Cunningham FG, Hoffman BL, Leveno KJ. et al, eds. Williams Obstetrics. 26th ed. New York, NY: McGraw-Hill Education; 2022: 981-986
14 Silver R, Lockwood C. Thrombosis, thrombosis, thrombophilia and thromboembolism. ACOG Clinical Update Women's. Health Care (Don Mills) 2016; XV (03) x
15 Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158 (06) 585-593
16 Stein PD, Matta F. Epidemiology and incidence: the scope of the problem and risk factors for development of venous thromboembolism. Clin Chest Med 2010; 31 (04) 611-628
17 Anderson Jr FA, Wheeler HB, Goldberg RJ. et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991; 151 (05) 933-938
18 Stein PD, Hull RD, Kayali F, Ghali WA, Alshab AK, Olson RE. Venous thromboembolism according to age: the impact of an aging population. Arch Intern Med 2004; 164 (20) 2260-2265
19 Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR, Hammerstrøm J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost 2007; 5 (04) 692-699
20 Tagalakis V, Patenaude V, Kahn SR, Suissa S. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE study cohort. Am J Med 2013; 126 (09) 832.e13-832.e21
21 Huang W, Goldberg RJ, Anderson FA, Kiefe CI, Spencer FA. Secular trends in occurrence of acute venous thromboembolism: the Worcester VTE study (1985-2009). Am J Med 2014; 127 (09) 829-39.e5
22 Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis 2016; 41 (01) 3-14
23 Barco S, Mahmoudpour SH, Valerio L. et al. Trends in mortality related to pulmonary embolism in the European Region, 2000-15: analysis of vital registration data from the WHO mortality database. Lancet Respir Med 2020; 8 (03) 277-287
24 Gherman RB, Goodwin TM, Leung B, Byrne JD, Hethumumi R, Montoro M. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstet Gynecol 1999; 94 (5 Pt 1): 730-734
25 Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton III LJ. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005; 143 (10) 697-706
26 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 (05) 1311-1315
27 Pomp ER, Lenselink AM, Rosendaal FR, Doggen CJ. Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study. J Thromb Haemost 2008; 6 (04) 632-637
28 Jacobsen AF, Skjeldestad FE, Sandset PM. Incidence and risk patterns of venous thromboembolism in pregnancy and puerperium–a register-based case-control study. Am J Obstet Gynecol 2008; 198 (02) 233.e1-233.e7
29 O'Connor DJ, Scher LA, Gargiulo III NJ, Jang J, Suggs WD, Lipsitz EC. Incidence and characteristics of venous thromboembolic disease during pregnancy and the postnatal period: a contemporary series. Ann Vasc Surg 2011; 25 (01) 9-14
30 Wells PS, Ginsberg JS, Anderson DR. et al. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med 1998; 129 (12) 997-1005
31 Klok FA, Mos IC, Nijkeuter M. et al. Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism. Arch Intern Med 2008; 168 (19) 2131-2136
32 O'Connor C, Moriarty J, Walsh J, Murray J, Coulter-Smith S, Boyd W. The application of a clinical risk stratification score may reduce unnecessary investigations for pulmonary embolism in pregnancy. J Matern Fetal Neonatal Med 2011; 24 (12) 1461-1464
33 van der Pol LM, Tromeur C, Bistervels IM. et al; Artemis Study Investigators. Pregnancy-adapted YEARS algorithm for diagnosis of suspected pulmonary embolism. N Engl J Med 2019; 380 (12) 1139-1149
34 Bremme K, Ostlund E, Almqvist I, Heinonen K, Blombäck M. Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium. Obstet Gynecol 1992; 80 (01) 132-137
35 Choi JW, Pai SH. Tissue plasminogen activator levels change with plasma fibrinogen concentrations during pregnancy. Ann Hematol 2002; 81 (11) 611-615
36 Chan WS, Chunilal S, Lee A, Crowther M, Rodger M, Ginsberg JS. A red blood cell agglutination D-dimer test to exclude deep venous thrombosis in pregnancy. Ann Intern Med 2007; 147 (03) 165-170
37 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 (05) 1004-1011
38 Murphy N, Broadhurst DI, Khashan AS, Gilligan O, Kenny LC, O'Donoghue K. Gestation-specific D-dimer reference ranges: a cross-sectional study. BJOG 2015; 122 (03) 395-400
39 Ercan Ş, Özkan S, Yücel N, Orçun A. Establishing reference intervals for D-dimer to trimesters. J Matern Fetal Neonatal Med 2015; 28 (08) 983-987
40 Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol 2009; 114 (06) 1326-1331
41 Parilla BV, Fournogerakis R, Archer A. et al. Diagnosing pulmonary embolism in pregnancy: are biomarkers and clinical predictive models useful?. AJP Rep 2016; 6 (02) e160-e164
42 Sekiya A, Hayashi T, Kadohira Y. et al. Thrombosis prediction based on reference ranges of coagulation-related markers in different stages of pregnancy. Clin Appl Thromb Hemost 2017; 23 (07) 844-850
43 Righini M, Robert-Ebadi H, Elias A. et al; CT-PE-Pregnancy Group. Diagnosis of pulmonary embolism during pregnancy: a multicenter prospective management outcome study. Ann Intern Med 2018; 169 (11) 766-773
44 Goodacre S, Horspool K, Nelson-Piercy C. et al; DiPEP research group. The DiPEP study: an observational study of the diagnostic accuracy of clinical assessment, D-dimer and chest x-ray for suspected pulmonary embolism in pregnancy and postpartum. BJOG 2019; 126 (03) 383-392
45 Duffett L, Castellucci LA, Forgie MA. Pulmonary embolism: update on management and controversies. BMJ 2020; 370: m2177