Elsevier

The Lancet Haematology

Volume 7, Issue 3, March 2020, Pages e247-e258
The Lancet Haematology

Review
Comparison of international societal guidelines for the diagnosis of suspected pulmonary embolism during pregnancy

https://doi.org/10.1016/S2352-3026(19)30250-9Get rights and content

Summary

Pregnancy-associated pulmonary embolism is one of the leading causes of maternal mortality. Diagnosis of pulmonary embolism in pregnancy is challenging, with symptoms of pulmonary embolism mimicking those of pregnancy. Several key components such as clinical prediction tools, risk stratification, laboratory tests, and imaging widely used for diagnosis of pulmonary embolism in the non-pregnant population show limitations for diagnosis in pregnancy. Further, because of the difficulty of studying pregnant patients, high-quality research evaluating the performance of these diagnostic components in pregnancy is scarce. Seven international medical society guidelines present clinical diagnostic pathways for evaluation of pulmonary embolism in pregnancy that show conflicting recommendations on the use of these diagnostic components. This Review assesses all key components of diagnostic clinical pathways recommended by guidelines for evaluation of pulmonary embolism in pregnancy, reviews current evidence, compares the guideline recommendations with respect to each key component, and provides our preferred diagnostic pathway. It provides the guidelines and available data needed for informed decision making to diagnose pulmonary embolism in pregnancy.

Introduction

Pulmonary embolism is one of the leading causes of death in pregnancy, with mortality estimated to be as high as 20%.1 Pregnancy is a state of hypercoagulability that increases the chance of developing venous thromboembolism, deep vein thrombosis, and pulmonary embolism, by five to ten fold when compared with the non-pregnant population.2 Untreated pulmonary embolism can result in 30% mortality, which is reduced to as low as 2% with anticoagulation treatment.3 Although minimal, anticoagulation carries a risk of haemorrhage.4 Early and accurate diagnosis of pulmonary embolism is thus crucial to reduce morbidity and mortality in pregnancy.

The symptoms of pulmonary embolism, such as tachycardia, tachypnoea, desaturation, dyspnoea, and pleuritic chest pain, mimic the normal physiological changes of pregnancy, thus making an accurate and timely diagnosis difficult relative to the non-pregnant population.5 To diagnose pulmonary embolism, clinicians commonly use several clinical key components (appendix p 1). However, many of these components, such as clinical prediction tools, risk stratification, and laboratory tests, have shown limited use in pregnancy.6, 7 Furthermore, because of the sensitive nature of evaluating pregnant patients, high-quality evidence data to assess the performance of these components in pregnancy are scarce and very few studies evaluate outcomes for a combination of tests in a prospective diagnostic algorithm.8, 9 As such, controversy exists for the best diagnostic algorithm for suspected pulmonary embolism in pregnancy, leading to variability in the investigations of pregnant patients with suspicion of pulmonary embolism in clinical care.

Seven international medical society guidelines address investigations of suspected pulmonary embolism in pregnancy.10, 11, 12, 13, 14, 15, 16 These guidelines vary in terms of components used and their application order. An important review by Wan and colleages17 compares these guidelines for a few of the diagnostic components including clinical prediction tools, D-dimer testing, lower extremity venous duplex scan (lower extremity ultrasound) before advanced imaging, and primary advanced imaging. However, this review does not compare the guidelines for risk stratification, empirical treatment, and follow-up of indeterminate results of advanced imaging.17 Further, since this review, a new version of one of the guidelines and two essential prospective clinical trials evaluating pulmonary embolism in pregnancy algorithms were published.8, 9, 13 The purpose of our Review is to assess all of the key components of the diagnostic clinical pathways recommended by guidelines for evaluation of pulmonary embolism in pregnancy, to review current evidence, to compare the most current guideline recommendations with respect to each key component, and to provide our preferred diagnostic pathway.

Section snippets

Guidelines

Each of the seven guidelines proposes a clinical pathway for diagnosis of pulmonary embolism in pregnancy. The guidelines discussed in this Review are proposed by the following societies: Australasian Society of Thrombosis and Haemostasis and the Society of Obstetric Medicine of Australia and New Zealand (ASTH-SOMANZ), American Thoracic Society and Society of Thoracic Radiology (ATS-STR), European Association of Nuclear Medicine (EANM), European Society of Cardiology (ESC), Working Group in

Clinical prediction

In non-pregnant patients, clinical prediction tools such as the Wells score and revised Geneva score are well established and used as a precursor for imaging in patients with suspected pulmonary embolism. Both scores are based on point systems of clinical characteristics to stratify patients at low, intermediate, or high risk.18, 19 These tools were created for non-pregnant patients with pregnancy as an exclusion criterion.19, 20 Consequently, these tools are based on factors such as patient

Our preferred diagnostic pathway

Our preferred diagnostic pathway based on available evidence is shown in panel 2 and the figure.

Future directions

Further research in the evaluation of pulmonary embolism in pregnancy is needed to establish the best diagnostic strategy. Clinical prediction tools designed specifically for pregnancy are needed, which can greatly reduce exposure to radiation and contrast. Empirical treatment can improve outcomes; however, further assessments of its risk–benefit profile in pregnancy is necessary. Although D-dimer testing has been successfully used in two prospective clinical trials, further studies are needed

Conclusion

Pulmonary embolism is one of the leading causes of mortality in pregnancy. This narrative Review discusses the key components of the diagnostic clinical pathways for evaluation of pulmonary embolism in pregnancy and discusses each component's current evidence and evidence needs, and compares guideline recommendations for each key component. This Review builds upon previous review articles by including more diagnostic components, the most up-to-date version of each guideline, and data from two

Search strategy and selection criteria

We searched PubMed to identify societal clinical guidelines published in English for the investigation of pulmonary embolism in pregnancy after the year 2000 for this Review. We searched for articles with at least one term from each of the following two categories: (1) “guideline”, “society”, “official”, “algorithm”, and “recommendation”; and (2) “deep vein thrombosis”, “pulmonary embolism”, “venous thromboembolism”, “ventilation”, “perfusion”, “scintigraphy”, “computed tomography”, “CT”,

References (75)

  • G Barillari et al.

    Recurrence of venous thromboembolism in patients with recent gestational deep vein thrombosis or pulmonary embolism: findings from the RIETE Registry

    Eur J Intern Med

    (2016)
  • HM Knol et al.

    The risk of postpartum hemorrhage in women using high dose of low-molecular-weight heparins during pregnancy

    Thromb Res

    (2012)
  • SK Dhillon et al.

    High-versus low-dose warfarin-related teratogenicity: a case report and systematic review

    J Obstet Gynaecol Can

    (2018)
  • MA Rodger et al.

    Meta-analysis of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications

    Blood

    (2014)
  • LM van der Pol et al.

    Use of clinical prediction rules and D-dimer tests in the diagnostic management of pregnant patients with suspected acute pulmonary embolism

    Blood Rev

    (2017)
  • KB Grossman et al.

    Maternal and pregnancy characteristics affect plasma fibrin monomer complexes and D-dimer reference ranges for venous thromboembolism in pregnancy

    Am J Obstet Gynecol

    (2016)
  • M Kovac 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)
  • M Wang et al.

    Reference intervals of D-dimer during the pregnancy and puerperium period on the STA-R evolution coagulation analyzer

    Clin Chim Acta

    (2013)
  • SG Fronas et al.

    Safety of D-dimer testing as a stand-alone test for the exclusion of deep vein thrombosis as compared with other strategies

    J Thromb Haemost

    (2018)
  • S Kawaguchi et al.

    Changes in D-dimer levels in pregnant women according to gestational week

    Pregnancy Hypertens

    (2013)
  • M Righini et al.

    Complete venous ultrasound in outpatients with suspected pulmonary embolism

    J Thromb Haemost

    (2009)
  • WS Chan

    Diagnosis of venous thromboembolism in pregnancy

    Thromb Res

    (2018)
  • C Gillespie et al.

    The OPTICA study (Optimised Computed Tomography Pulmonary Angiography in Pregnancy Quality and Safety study): rationale and design of a prospective trial assessing the quality and safety of an optimised CTPA protocol in pregnancy

    Thromb Res

    (2019)
  • KR Burton et al.

    Risk of early-onset breast cancer among women exposed to thoracic computed tomography in pregnancy or early postpartum

    J Thromb Haemost

    (2018)
  • J Kooiman et al.

    Meta-analysis: serum creatinine changes following contrast enhanced CT imaging

    Eur J Radiol

    (2012)
  • R Cantwell et al.

    Saving mothers' lives: reviewing maternal deaths to make motherhood safer: 2006-2008. The eighth report of the confidential enquiries into maternal deaths in the United Kingdom

    BJOG

    (2011)
  • EH Wang et al.

    Haemorrhagic complications of peripartum anticoagulation: a retrospective chart review

    Obstet Med

    (2014)
  • R Ramsay et al.

    The problem of pulmonary embolism diagnosis in pregnancy

    Br J Haematol

    (2015)
  • KK Hedengran et al.

    Large D-dimer fluctuation in normal pregnancy: a longitudinal cohort study of 4,117 samples from 714 healthy Danish women

    Obstet Gynecol Int

    (2016)
  • JJ Michiels et al.

    A critical appraisal of non-invasive diagnosis and exclusion of deep vein thrombosis and pulmonary embolism in outpatients with suspected deep vein thrombosis or pulmonary embolism: how many tests do we need?

    Int Angiol

    (2005)
  • M Righini et al.

    Diagnosis of pulmonary embolism during pregnancy: a multicenter prospective management outcome study

    Ann Intern Med

    (2018)
  • LM van der Pol et al.

    Pregnancy-adapted YEARS algorithm for diagnosis of suspected pulmonary embolism

    N Engl J Med

    (2019)
  • C McLintock et al.

    Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period

    Aust N Z J Obstet Gynaecol

    (2012)
  • AN Leung 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)
  • M Bajc et al.

    EANM guidelines for ventilation/perfusion scintigraphy: Part 2. Algorithms and clinical considerations for diagnosis of pulmonary emboli with V/P(SPECT) and MDCT

    Eur J Nucl Med Mol Imaging

    (2009)
  • SV Konstantinides et al.

    2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)

    Eur Respir J

    (2019)
  • B Linnemann et al.

    Diagnosis of pregnancy-associated venous thromboembolism—position paper of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH)

    Vasa

    (2016)
  • Cited by (36)

    • Letter From the Editors

      2023, Seminars in Nuclear Medicine
    • Excluding pregnancy-associated deep vein thrombosis with whole-leg ultrasound

      2023, Research and Practice in Thrombosis and Haemostasis
    View all citing articles on Scopus
    View full text