Risk Factors for Major Bleeding During Anticoagulation Therapy in Cancer-Associated Venous Thromboembolism - From the COMMAND VTE Registry

Circ J. 2020 Oct 23;84(11):2006-2014. doi: 10.1253/circj.CJ-20-0223. Epub 2020 Oct 3.


Background: Patients with cancer-associated venous thromboembolism (VTE) are at high risk for recurrent VTE and are recommended to receive prolonged anticoagulation therapy if they are at a low risk for bleeding. However, there are no established risk factors for bleeding during anticoagulation therapy.Methods and Results:The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3,027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 592 cancer-associated VTE patients with anticoagulation therapy. We constructed a multivariable Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the potential risk factors for major bleeding. During a median follow-up period of 199 days, major bleeding occurred in 72 patients. The cumulative incidence of major bleeding was 5.8% at 3 months, 13.8% at 1 year, 17.5% at 2 years, and 28.1% at 5 years. The most frequent major bleeding site was gastrointestinal tract (47%). Terminal cancer (adjusted HR, 4.17; 95% CI, 2.22-7.85, P<0.001), chronic kidney disease (adjusted HR, 1.89; 95% CI 1.06-3.37, P=0.031), and gastrointestinal cancer (adjusted HR, 1.78; 95% CI, 1.04-3.04, P=0.037) were independently associated with an increased risk of major bleeding.

Conclusions: Major bleeding events were common during anticoagulation therapy in real-world cancer-associated VTE patients. Terminal cancer, chronic kidney disease, and gastrointestinal cancer were the independent risk factors for major bleeding.

Keywords: Anticoagulants; Cancer; Hemorrhage; Risk assessment; Venous thromboembolism.

Publication types

  • Multicenter Study

MeSH terms

  • Anticoagulants / therapeutic use*
  • Hemorrhage* / epidemiology
  • Humans
  • Japan
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Recurrence
  • Registries
  • Renal Insufficiency, Chronic
  • Retrospective Studies
  • Risk Factors
  • Venous Thromboembolism* / drug therapy
  • Venous Thromboembolism* / etiology


  • Anticoagulants