Elsevier

The Lancet

Volume 388, Issue 10063, 17 December 2016–6 January 2017, Pages 3060-3073
The Lancet

Seminar
Deep vein thrombosis and pulmonary embolism

https://doi.org/10.1016/S0140-6736(16)30514-1Get rights and content

Summary

Deep vein thrombosis and pulmonary embolism, collectively referred to as venous thromboembolism, constitute a major global burden of disease. The diagnostic work-up of suspected deep vein thrombosis or pulmonary embolism includes the sequential application of a clinical decision rule and D-dimer testing. Imaging and anticoagulation can be safely withheld in patients who are unlikely to have venous thromboembolism and have a normal D-dimer. All other patients should undergo ultrasonography in case of suspected deep vein thrombosis and CT in case of suspected pulmonary embolism. Direct oral anticoagulants are first-line treatment options for venous thromboembolism because they are associated with a lower risk of bleeding than vitamin K antagonists and are easier to use. Use of thrombolysis should be limited to pulmonary embolism associated with haemodynamic instability. Anticoagulant treatment should be continued for at least 3 months to prevent early recurrences. When venous thromboembolism is unprovoked or secondary to persistent risk factors, extended treatment beyond this period should be considered when the risk of recurrence outweighs the risk of major bleeding.

Introduction

Deep vein thrombosis and pulmonary embolism are manifestations of venous thromboembolism. Although deep vein thrombosis develops most often in the legs, the deep veins of the arms, the splanchnic veins, and the cerebral veins can be affected. In this Seminar we focus on the epidemiology, diagnosis, and treatment of deep vein thrombosis of the legs and pulmonary embolism. Prevention of venous thromboembolism is outside the scope of this Seminar.

Section snippets

Epidemiology

Venous thromboembolism is a major global burden with about 10 million cases occurring every year, thereby representing the third leading vascular disease after acute myocardial infarction and stroke.1 Just under half a million deep vein thromboses and 300 000 pulmonary embolisms occur every year in six European countries with 300 million inhabitants.2 The yearly economic burden of venous thromboembolism in the USA has been estimated to be US$7–10 billion.3 Incidence is steadily increasing

Clinical presentation

Clinical manifestations of deep vein thrombosis of the legs include swelling or pitting oedema, redness, tenderness, and presence of collateral superficial veins. Signs and symptoms of pulmonary embolism comprise sudden onset of dyspnoea or deterioration of existing dyspnoea, chest pain, syncope or dizziness due to hypotension or shock, haemoptysis, tachycardia, or tachypnoea. Abnormalities on chest radiography, electrocardiography, or blood gas analysis are not specific for pulmonary embolism,

Anticoagulant therapy

Anticoagulant therapy is the mainstay for the treatment of venous thromboembolism and is classically divided into three phases: the acute phase of the first 5–10 days after venous thromboembolism diagnosis, a maintenance phase of 3–6 months, and an extended phase beyond this period.85 During the acute phase, treatment options include subcutaneous low-molecular-weight heparin or fondaparinux, intravenous unfractionated heparin, or the direct oral factor Xa inhibitors rivaroxaban and apixaban (

Future research

Venous thromboembolism is a common disease accounting for major global morbidity and mortality. A wide range of physicians are involved in its diagnostic and therapeutic management. The introduction of direct oral anticoagulants has marked the beginning of a new era in the treatment of venous thromboembolism; however, many diagnostic and therapeutic research questions are still unanswered. Does the widespread use of imaging in combination with advances in imaging techniques truly result in

Search strategy and selection criteria

We searched MEDLINE, Embase, and the Cochrane Library for papers published in English from Dec 1, 2009, to March 31, 2016, using combinations of the following terms: “deep vein thrombosis”, “pulmonary embolism”, “venous thromboembolism”, “epidemiology”, “diagnosis”, “prognosis”, and “treatment”. We gave preference to publications from the past 5 years, but did consider highly regarded older publications. We screened the reference lists of articles identified by the search strategy and included

References (156)

  • PS Wells et al.

    Value of assessment of pretest probability of deep-vein thrombosis in clinical management

    Lancet

    (1997)
  • M Di Nisio et al.

    Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review

    J Thromb Haemost

    (2007)
  • ICM Mos et al.

    Diagnostic outcome management study in patients with clinically suspected recurrent acute pulmonary embolism with a structured algorithm

    Thromb Res

    (2014)
  • A Penaloza et al.

    Performance of age-adjusted D-dimer cut-off to rule out pulmonary embolism

    J Thromb Haemost

    (2012)
  • O Hugli et al.

    The pulmonary embolism rule-out criteria (PERC) rule does not safely exclude pulmonary embolism

    J Thromb Haemost

    (2011)
  • SM Bates et al.

    Diagnosis of DVT: antithrombotic therapy and prevention of thrombosis, 9th edn. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

    Chest

    (2012)
  • G Camporese et al.

    Outcome of patients with suspected lower limb symptomatic deep vein thrombosis and a normal ultrasound-based initial diagnostic workup: a prospective study

    J Thromb Haemost

    (2012)
  • G Palareti

    How I treat isolated distal deep vein thrombosis (IDDVT)

    Blood

    (2014)
  • W Ageno et al.

    Analysis of an algorithm incorporating limited and whole-leg assessment of the deep venous system in symptomatic outpatients with suspected deep-vein thrombosis (PALLADIO): a prospective, multicentre, cohort study

    Lancet Haematol

    (2015)
  • L-A Linkins et al.

    Interobserver agreement on ultrasound measurements of residual vein diameter, thrombus echogenicity and Doppler venous flow in patients with previous venous thrombosis

    Thromb Res

    (2006)
  • M Tan et al.

    Magnetic resonance direct thrombus imaging differentiates acute recurrent ipsilateral deep vein thrombosis from residual thrombosis

    Blood

    (2014)
  • EJR Van Beek et al.

    Clinical validity of a normal pulmonary angiogram in patients with suspected pulmonary embolism—a critical review

    Clin Radiol

    (2001)
  • M.V. Huisman et al.

    Diagnostic management of clinically suspected acute pulmonary embolism

    J Thromb Haemost

    (2009)
  • M Carrier et al.

    Symptomatic subsegmental pulmonary embolism: what is the next step?

    J Thromb Haemost

    (2012)
  • M Righini 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)
  • W Ageno et al.

    The diagnosis of symptomatic recurrent pulmonary embolism and deep vein thrombosis: guidance from the SSC of the ISTH

    J Thromb Haemost

    (2013)
  • M V Huisman et al.

    Magnetic resonance imaging for diagnosis of acute pulmonary embolism: not yet a suitable alternative to CT-PA

    J Thromb Haemost

    (2012)
  • L-A Linkins

    Treatment and prevention of heparin-induced thrombocytopenia

    Chest

    (2012)
  • N van Es et al.

    Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials

    Blood

    (2014)
  • C Kearon et al.

    Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report

    Chest

    (2016)
  • W Ageno et al.

    Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study

    Lancet Haematol

    (2016)
  • GE Raskob et al.

    Thrombosis: a major contributor to global disease burden

    Arterioscler Thromb Vasc Biol

    (2014)
  • AT Cohen et al.

    Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality

    Thromb Haemost

    (2007)
  • H Jensvoll et al.

    Existing data sources in clinical epidemiology: the Scandinavian Thrombosis and Cancer Cohort

    Clin Epidemiol

    (2015)
  • JA Heit

    Epidemiology of venous thromboembolism

    Nat Rev Cardiol

    (2015)
  • SB Deitelzweig et al.

    Venous thromboembolism in the US: does race matter?

    J Thromb Thrombolysis

    (2011)
  • REJ Roach et al.

    Sex difference in risk of second but not of first venous thrombosis: paradox explained

    Circulation

    (2014)
  • KK Sogaard et al.

    30-year mortality after venous thromboembolism: a population-based cohort study

    Circulation

    (2014)
  • PD Stein et al.

    Trends in case fatality rate in pulmonary embolism according to stability and treatment

    Thromb Res

    (2012)
  • C Kearon

    Natural history of venous thromboembolism

    Circulation

    (2003)
  • SR Kahn et al.

    The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies

    Circulation

    (2014)
  • C Kearon et al.

    Categorization of patients as having provoked or unprovoked VTE: guidance from the SSC of ISTH

    J Thromb Haemost

    (2016)
  • J-M Januel et al.

    Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis: a systematic review

    JAMA

    (2012)
  • P MacCallum et al.

    Diagnosis and management of heritable thrombophilias

    BMJ

    (2014)
  • P-E Morange et al.

    Genetics of venous thrombosis: update in 2015

    Thromb Haemost

    (2015)
  • W Lucassen et al.

    Clinical decision rules for excluding pulmonary embolism: a meta-analysis

    Ann Intern Med

    (2011)
  • GJ Geersing et al.

    Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis

    BMJ

    (2014)
  • PS Wells et al.

    Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis

    N Engl J Med

    (2003)
  • PS Wells et al.

    Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer

    Thromb Haemost

    (2000)
  • NS Gibson et al.

    Further validation and simplification of the Wells clinical decision rule in pulmonary embolism

    Thromb Haemost

    (2008)
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