Diagnosis and Treatment of Lower Extremity Venous Thromboembolism: A Review

JAMA. 2020 Nov 3;324(17):1765-1776. doi: 10.1001/jama.2020.17272.


Importance: Incidence rates for lower extremity deep vein thrombosis (DVT) range from 88 to 112 per 100 000 person-years and increase with age. Rates of recurrent VTE range from 20% to 36% during the 10 years after an initial event.

Observations: PubMed and Cochrane databases were searched for English-language studies published from January 2015 through June 2020 for randomized clinical trials, meta-analyses, systematic reviews, and observational studies. Risk factors for venous thromboembolism (VTE), such as older age, malignancy (cumulative incidence of 7.4% after a median of 19 months), inflammatory disorders (VTE risk is 4.7% in patients with rheumatoid arthritis and 2.5% in those without), and inherited thrombophilia (factor V Leiden carriers with a 10-year cumulative incidence of 10.9%), are associated with higher risk of VTE. Patients with signs or symptoms of lower extremity DVT, such as swelling (71%) or a cramping or pulling discomfort in the thigh or calf (53%), should undergo assessment of pretest probability followed by D-dimer testing and imaging with venous ultrasonography. A normal D-dimer level (ie, D-dimer <500 ng/mL) excludes acute VTE when combined with a low pretest probability (ie, Wells DVT score ≤1). In patients with a high pretest probability, the negative predictive value of a D-dimer less than 500 ng/mL is 92%. Consequently, D-dimer cannot be used to exclude DVT without an assessment of pretest probability. Postthrombotic syndrome, defined as persistent symptoms, signs of chronic venous insufficiency, or both, occurs in 25% to 50% of patients 3 to 6 months after DVT diagnosis. Catheter-directed fibrinolysis with or without mechanical thrombectomy is appropriate in those with iliofemoral obstruction, severe symptoms, and a low risk of bleeding. The efficacy of direct oral anticoagulants-rivaroxaban, apixaban, dabigatran, and edoxaban-is noninferior to warfarin (absolute rate of recurrent VTE or VTE-related death, 2.0% vs 2.2%). Major bleeding occurs in 1.1% of patients treated with direct oral anticoagulants vs 1.8% treated with warfarin.

Conclusions and relevance: Greater recognition of VTE risk factors and advances in anticoagulation have facilitated the clinical evaluation and treatment of patients with DVT. Direct oral anticoagulants are noninferior to warfarin with regard to efficacy and are associated with lower rates of bleeding, but costs limit use for some patients.

Publication types

  • Systematic Review

MeSH terms

  • Age Factors
  • Biomarkers / blood
  • Factor Xa Inhibitors / adverse effects
  • Factor Xa Inhibitors / therapeutic use
  • Fibrin Fibrinogen Degradation Products / analysis
  • Humans
  • Life Style
  • Lower Extremity / blood supply*
  • Medical Illustration
  • Postthrombotic Syndrome / etiology
  • Predictive Value of Tests
  • Risk Factors
  • Sex Factors
  • Symptom Assessment
  • Thrombectomy / methods
  • Thrombophilia / complications
  • Thrombophilia / genetics
  • Ultrasonography
  • Vena Cava Filters
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / diagnosis*
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / therapy*
  • Warfarin / therapeutic use


  • Biomarkers
  • Factor Xa Inhibitors
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • Warfarin