Elsevier

The Lancet

Volume 375, Issue 9713, 6–12 February 2010, Pages 500-512
The Lancet

Seminar
Pulmonary embolism in pregnancy

https://doi.org/10.1016/S0140-6736(09)60996-XGet rights and content

Summary

Pulmonary embolism (PE) is the leading cause of maternal mortality in the developed world. Mortality from PE in pregnancy might be related to challenges in targeting the right population for prevention, ensuring that diagnosis is suspected and adequately investigated, and initiating timely and best possible treatment of this disease. Pregnancy is an example of Virchow's triad: hypercoagulability, venous stasis, and vascular damage; together these factors lead to an increased incidence of venous thromboembolism. This disorder is often suspected in pregnant women because some of the physiological changes of pregnancy mimic its signs and symptoms. Despite concerns for fetal teratogenicity and oncogenicity associated with diagnostic testing, and potential adverse effects of pharmacological treatment, an accurate diagnosis of PE and a timely therapeutic intervention are crucial. Appropriate prophylaxis should be weighed against the risk of complications and offered according to risk stratification.

Introduction

Peripartum haemorrhage is the leading cause of maternal mortality in the developing world, reflecting the haemostatic challenge of childbirth.1 The maternal hypercoagulable state is a physiological preparation for delivery; however, this hypercoagulability is associated with an increased risk of venous thromboembolism (VTE). Indeed, in the developed world, where the haemostatic challenge of delivery is mitigated by modern obstetrical practices, VTE is the leading cause of maternal mortality.2, 3, 4, 5, 6

Prevention, diagnosis, and therapeutic management of pulmonary embolism (PE) in pregnant women are all complicated by a shortage of validated approaches in this unique population. In this Seminar, we provide practical recommendations to overcome these challenges.

Section snippets

Epidemiology

The incidence of VTE in pregnant women, derived from retrospective cohort studies, is estimated to be 5–12 events per 10 000 pregnancies antenatally (from conception to delivery), seven to ten times higher than the incidence in age-matched controls. The risk of VTE events is similar in all three trimesters.7 The incidence of pregnancy-associated deep vein thrombosis (DVT) is about three times higher than that of pregnancy-associated PE.8 Pregnancy-associated DVT is left sided in over 85% of

Pathophysiology

The elements of Virchow's triad—venous stasis, vascular damage, and hypercoagulability—are all present during pregnancy and the postpartum period (figure 1). Venous stasis, which begins in the first trimester and reaches a peak at 36 weeks of gestation, is probably caused by progesterone-induced venodilation, pelvic venous compression by the gravid uterus, and pulsatile compression of the left iliac vein by the right iliac artery.19 Additional damage to the pelvic vessels results from normal

Diagnosis

Approaches to diagnostic management of suspected PE in pregnancy have not been validated. The following suggestions are based on a combination of limited data for diagnosis of suspected PE in pregnancy and more abundant data for non-pregnant patients.

A major challenge in the diagnostic management of suspected PE is to reduce the number of false-negative and false-positive results. False-negative results are a concern because untreated VTE, at least outside of pregnancy, has a mortality rate as

Treatment of confirmed PE in pregnancy

LMWH is the treatment of choice for PE in pregnant and non-pregnant patients. LMWH is at least as effective and as safe as UFH in non-pregnant women for the treatment of acute VTE.78, 79 Furthermore, long-term use of LMWH seems as safe and effective as vitamin K antagonists for the prevention of recurrent VTE in non-pregnant patients.78, 79, 80, 81, 82

Treatment of PE can be considered in four phases: acute (first 24 h from diagnosis), subacute (day 1–30), medium term (1–6 months) and long term

Management of isolated subsegmental PE

The shortage of data on clinical outcomes in pregnant or non-pregnant patients with isolated subsegmental PE in whom anticoagulation has been withheld makes management of these emboli difficult. Outcome data for patients who had ventilation perfusion scans interpreted as normal indirectly supports withholding anticoagulation in patients with normal perfusion in the same distribution as a subsegmental PE detected on CT. However, diagnostic and therapeutic management of isolated subsegmental PE

Prevention

Risk assessment should be done to establish the need for thromboprophylaxis during pregnancy and the postpartum period. However, large-scale studies on VTE prophylaxis are scarce; therefore, recommendations are based on studies done in non-pregnant patients, case series of pregnant patients, and consensus recommendations.123, 125 Early mobilisation and graduated compression stockings are mildly effective, safe, and non-invasive methods for prevention of VTE;126 they are probably all that is

Conclusions

The diagnosis and management of PE in pregnancy is complicated by the physiological changes of pregnancy and the paucity of studies done in pregnant patients. Specific areas of future research should concentrate on the following key areas: determination of clinical criteria that would help to predict the likelihood of VTE; assessment of current and new biomarkers of the prothrombotic state, such as D-dimer concentration, and their incorporation into algorithms of thrombotic risk assessment in

Search strategy and selection criteria

We searched Medline (1996–2008), PubMed (1996–2008), and the Global Health (2002–08), Popline (2002–08), and Cochrane (2002–08) databases with the MeSH headings “pulmonary embolism”, “venous thromboembolism”, “subsegmental emboli”, “pregnancy”, “mortality”, “epidemiology”, “risk factors”, “diagnosis”, “arterial blood gases”, “electrocardiogram”, “ventilation perfusion scan”, “computed tomography pulmonary angiogram”, “magnetic resonance”, “compression ultrasonography”, “echocardiogram”,

References (135)

  • ER Pomp et al.

    Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study

    J Thromb Haemost

    (2008)
  • AH James et al.

    Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality

    Am J Obstet Gynecol

    (2006)
  • DR Danilenko-Dixon et al.

    Risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum: a population-based, case-control study

    Am J Obstet Gynecol

    (2001)
  • AF Jacobsen et al.

    Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study

    J Thromb Haemost

    (2008)
  • E Grandone et al.

    Genetic susceptibility to pregnancy-related venous thromboembolism: roles of factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations

    Am J Obstet Gynecol

    (1998)
  • J Ginsberg et al.

    Antiphospholipid antibodies and venous thromboembolism

    Blood

    (1995)
  • TB Larsen et al.

    Maternal smoking, obesity, and risk of venous thromboembolism during pregnancy and the puerperium: a population-based nested case-control study

    Thromb Res

    (2007)
  • RM Bauersachs et al.

    More on the “ART” behind the clot: solving the mystery

    J Thromb Haemost

    (2007)
  • H Jick et al.

    Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components

    Lancet

    (1995)
  • A Perrier et al.

    Non-invasive diagnosis of venous thromboembolism in outpatients

    Lancet

    (1999)
  • MA Rodger et al.

    The interobserver reliability of pretest probability assessment in patients with suspected pulmonary embolism

    Thromb Res

    (2005)
  • M Carrier et al.

    Excluding pulmonary embolism at the bedside with low pre-test probability and D-dimer: safety and clinical utility of 4 methods to assign pre-test probability

    Thromb Res

    (2006)
  • M Rodger et al.

    Diagnostic value of the electrocardiogram in suspected pulmonary embolism

    Am J Cardiol

    (2000)
  • RO Powrie et al.

    Alveolar-arterial oxygen gradient in acute pulmonary embolism in pregnancy

    Am J Obstet Gynecol

    (1998)
  • M Morse

    Establishing a normal range for D-dimer levels through pregnancy to aid in the diagnosis of pulmonary embolism and deep vein thrombosis

    J Thromb Haemost

    (2004)
  • J Valentin

    Biological effects after prenatal irradiation-embryo and fetus (International Commission on Radiological Protection publication 90)

    Ann ICRP

    (2003)
  • RL Brent

    Saving lives and changing family histories: appropriate counseling of pregnant women and men and women of reproductive age, concerning the risk of diagnostic radiation exposures during and before pregnancy

    Am J Obstet Gynecol

    (2009)
  • N Doyle et al.

    Diagnosis of pulmonary embolism: a cost-effectiveness analysis

    Am J Obstet Gynecol

    (2004)
  • P Prandoni et al.

    Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis

    Blood

    (2002)
  • PD Stein et al.

    Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy

    Chest

    (1995)
  • IA Greer et al.

    Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy

    Blood

    (2005)
  • N Martel et al.

    Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis

    Blood

    (2005)
  • JC Malcolm et al.

    Use of low molecular weight heparin in acute venous thromboembolic events in pregnancy

    J Obstet Gynaecol Can

    (2002)
  • HL Casele et al.

    Changes in the pharmacokinetics of the low-molecular-weight heparin enoxaparin sodium during pregnancy

    Am J Obstet Gynecol

    (1999)
  • EA Sullivan et al.

    Maternal mortality in Australia, 1973–1996

    Aust N Z J Obstet Gynaecol

    (2004)
  • M Legnain et al.

    Maternal mortality in Benghazi. A clinical epidemiological study

    East Mediterr Health J

    (2000)
  • T Kobayashi et al.

    Pulmonary thromboembolism in obstetrics and gynecology increased by 6·5-fold over the past decade in Japan

    Circ J

    (2008)
  • JG Ray et al.

    Deep vein thrombosis during pregnancy and the puerperium: a meta analysis of the period of risk and the leg of presentation

    Obstet Gynecol Surv

    (1999)
  • JA Heit et al.

    Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30 year population based study

    Ann Intern Med

    (2005)
  • BS Andersen et al.

    The cumulative incidence of venous thromboembolism during pregnancy and puerperium. An 11 year Danish population-based study of 63,300 pregnancies

    Acta Obstet Gynecol Scand

    (1998)
  • U Kjellberg et al.

    APC resistance and other haemostatic variables during pregnancy and puerperium

    Thromb Haemost

    (1999)
  • NS Macklon et al.

    An ultrasound study of gestational and postural changes in the deep venous system of the leg in pregnancy

    Br J Obstet Gynaecol

    (1997)
  • P Clark et al.

    Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy

    Thromb Haemost

    (1998)
  • A Rosenkranz et al.

    Calibrated automated thrombin generation in normal uncomplicated pregnancy

    Thromb Haemost

    (2008)
  • MD McColl et al.

    Risk factors for pregnancy associated venous thromboembolism

    Thromb Haemost

    (1997)
  • Blanco-Molina et al.

    Venous thromboembolism during pregnancy or postpartum: Findings from the RIETE Registry

    Thromb Haemost

    (2007)
  • C van Walraven et al.

    Risk of subsequent thromboembolism for patients with pre-eclampsia

    BMJ

    (2003)
  • GA Rosito et al.

    Association between obesity and a prothrombotic state: the Framingham Offspring Study

    Thromb Haemost

    (2004)
  • KW Lee et al.

    Effects of lifestyle on hemostasis, fibrinolysis, and platelet reactivity: a systematic review

    Arch Intern Med

    (2003)
  • JL Carson et al.

    The clinical course of pulmonary embolism

    N Engl J Med

    (1992)
  • Cited by (247)

    • Update on venous thromboembolism in pregnancy

      2023, JMV-Journal de Medecine Vasculaire
    View all citing articles on Scopus
    View full text