Recurrent venous thromboembolism in anticoagulated patients with cancer: management and short-term prognosis

J Thromb Haemost. 2015 Jun;13(6):1010-8. doi: 10.1111/jth.12955. Epub 2015 May 9.

Abstract

Background: Recommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagulation strategies.

Methods: Patients with cancer and VTE despite anticoagulant therapy were reported to the registry. Data on treatments, VTE events, major bleeding, residual thrombosis symptoms and death were collected for the following 3 months. Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes with different treatment strategies were compared with Cox proportional hazards regression.

Results: We registered 212 patients with breakthrough VTE. Of those, 59% had adenocarcinoma and 73% had known metastases. At the time of the breakthrough event, 70% were on low-molecular-weight heparin (LMWH) and 27% on a vitamin K antagonist (VKA); 70% had a therapeutic or supratherapeutic dose. After breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased in 31%, switched to another drug in 24%; and other management in 11%. During the following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence was less common with LMWH than with a VKA (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.11-0.70) but similar with unchanged or increased anticoagulant intensity (HR, 1.09; 95% CI, 0.45-2.63). The bleeding rate did not increase significantly with dose escalation.

Conclusion: Morbidity and mortality are high after recurrence of cancer-related VTE despite anticoagulation. Further treatment appears to be more effective with LMWH than with a VKA.

Keywords: bleeding; cancer; low-molecular-weight heparin; venous thromboembolism; warfarin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Chi-Square Distribution
  • Drug Substitution
  • Female
  • Hemorrhage / chemically induced
  • Heparin, Low-Molecular-Weight / administration & dosage*
  • Heparin, Low-Molecular-Weight / adverse effects
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasms / blood
  • Neoplasms / complications*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Proportional Hazards Models
  • Prospective Studies
  • Recurrence
  • Registries
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / mortality
  • Vitamin K / antagonists & inhibitors
  • Warfarin / administration & dosage*
  • Warfarin / adverse effects

Substances

  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Vitamin K
  • Warfarin