Elsevier

The Lancet

Volume 398, Issue 10294, 3–9 July 2021, Pages 64-77
The Lancet

Seminar
Venous thromboembolism

https://doi.org/10.1016/S0140-6736(20)32658-1Get rights and content

Summary

Venous thromboembolism, comprising both deep vein thrombosis and pulmonary embolism, is a chronic illness that affects nearly 10 million people every year worldwide. Strong provoking risk factors for venous thromboembolism include major surgery and active cancer, but most events are unprovoked. Diagnosis requires a sequential work-up that combines assessment of clinical pretest probability for venous thromboembolism using a clinical score (eg, Wells score), D-dimer testing, and imaging. Venous thromboembolism can be considered excluded in patients with both a non-high clinical pretest probability and normal D-dimer concentrations. When required, ultrasonography should be done for a suspected deep vein thrombosis and CT or ventilation–perfusion scintigraphy for a suspected pulmonary embolism. Direct oral anticoagulants (DOACs) are the first-line treatment for almost all patients with venous thromboembolism (including those with cancer). After completing 3–6 months of initial treatment, anticoagulation can be discontinued in patients with venous thromboembolism provoked by a major transient risk factor. Patients whose long-term risk of recurrent venous thromboembolism outweighs the long-term risk of major bleeding, such as those with active cancer or men with unprovoked venous thromboembolism, should receive indefinite anticoagulant treatment. Pharmacological venous thromboembolism prophylaxis is generally warranted in patients undergoing major orthopaedic or cancer surgery. Ongoing research is focused on improving diagnostic strategies for suspected deep vein thrombosis, comparing different DOACs, developing safer anticoagulants, and further individualising approaches for the prevention and management of venous thromboembolism.

Introduction

Venous thromboembolism includes deep vein thrombosis and pulmonary embolism. Deep vein thrombosis most often occurs in the leg vein but can also develop in the splanchnic, cerebral, and arm veins. In this Seminar, we focus on recent (past 5 years) advances in epidemiology, pathophysiology, diagnosis, treatment, and prevention of deep vein thrombosis of the legs and pulmonary embolism. Future directions are also discussed.

Section snippets

Epidemiology

Afflicting worldwide nearly 10 million people of all ethnicities per year, venous thromboembolism is a substantial contributor to the global burden of disease.1 The annual incidence of acute venous thromboembolism is 1–2 cases per 1000 population,1, 2, 3 which rises exponentially with age for both men and women,2 and is 4-times higher in high-income than low-income countries.4 The lifetime risk of venous thromboembolism does not differ by sex, but women have a higher risk during the ages of

Pathophysiology

Venous thromboembolism is a multicausal disease believed to be triggered by interactions between multiple provoking factors (panel 1) that can be additive or synergistic. These provoking factors are thought to lead to clinically overt disease when a so-called thrombosis threshold is reached. Some clinical risk factors are strong and might result in venous thromboembolism without the presence of any other risk factors. These strong provoking factors can be transient or persistent. Strong

Diagnosis

The diagnostic approach to suspected venous thromboembolism comprises a sequential work-up combining assessment of clinical pretest probability, D-dimer testing, and imaging. The aim of this diagnostic work-up, which should be done ideally within 24 h of presentation, is to identify patients in whom anticoagulation should be initiated (that is, to confirm venous thromboembolism), and those in whom imaging and anticoagulation can be safely withheld (that is, to exclude venous thromboembolism).

Treatment

Treatment of venous thromboembolism aims to prevent thrombus extension and embolisation, cardiopulmonary collapse, death, recurrent venous thromboembolism, and the risk for long-term complications. Direct oral anticoagulants (DOACs), including the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, and the thrombin inhibitor dabigatran represent major advances in the therapeutic management of venous thromboembolism.77 The key aspects of DOACs, including development, pharmacological

Prevention

Appropriate and timely use of measures to prevent venous thromboembolism (hereafter referred to as thromboprophylaxis) in patients at risk for venous thromboembolism are imperative in reducing its global burden. Pharmacological thromboprophylaxis is generally warranted in patient groups in whom the risk of venous thromboembolism is higher than the risk of bleeding, such as patients undergoing major orthopaedic or cancer surgery.146 Individual risk assessment should be done in patient groups in

Future directions

New insights into the pathophysiological mechanisms of venous thrombosis have enhanced our understanding of venous thromboembolism. Advances in diagnostic, therapeutic, and prophylactic strategies have enabled a more individualised approach to patient care, and additional research addressing important clinical questions is ongoing. For example, whether strategies similar to the age-adjusted or pretest probability-adjusted D-dimer can also improve the diagnostic work-up of suspected deep vein

Search strategy and selection criteria

We searched MEDLINE, Embase, and the Cochrane Library for prospective studies and systematic reviews published in English between Jan 1, 2015, and March 31, 2021, using combinations of the following terms: “deep vein thrombosis”, “pulmonary embolism”, “venous thromboembolism”, “epidemiology”, “pathophysiology”, “diagnosis”, “treatment”, and “prevention”. We also searched CLOT+, a continuously updated repository of pre-appraised, best evidence to support practising physicians in clinical

Declaration of interests

TT reports travel and congress fees from Pfizer, and research grant support from the Swiss National Science Foundation (SNSF P2ZHP3_177999) and the CanVECTOR Network. SRK has been part of the advisory board for Pfizer, Sanofi, and Servier. FK and MAR declare no competing interests.

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