Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients

J Thromb Haemost. 2009 May;7(5):760-5. doi: 10.1111/j.1538-7836.2009.03326.x. Epub 2009 Feb 24.


Summary background: Cancer patients with venous thromboembolism (VTE) are at high risk of recurrent VTE despite standard anticoagulation. To date, very little published literature is available to guide the treatment of cancer patients with recurrent VTE.

Objectives: To evaluate the benefit and risk of low molecular weight heparin (LMWH) dose escalation in cancer patients with recurrent VTE.

Patients and methods: This was a retrospective cohort study of consecutive cancer outpatients referred for management of a symptomatic, recurrent VTE while receiving an anticoagulant. Confirmed episodes of recurrent VTE were treated with either dose escalation of LMWH in patients already anticoagulated with LMWH, or initiation of therapeutic dose LMWH in patients who were taking a vitamin K antagonist (VKA). All patients were followed for a minimum of 3 months after the index recurrent VTE unless they died during this period.

Results: Seventy cancer patients with a recurrent VTE despite ongoing anticoagulation were included. At the time of the recurrence, 67% of patients were receiving LMWH, and 33% were receiving a VKA. A total of six patients [8.6%; 95% confidence interval (CI) 4.0-17.5%] had a second recurrent VTE during the 3-month follow-up period, at an event rate of 9.9 per 100 patient-years (95% CI 2.0-17.8%). Three patients (4.3%; 95% CI 1.5-11.9%), or 4.8 per 100 patient-years (95% CI 0.0-10.3%) of follow-up, had bleeding complications. The median time between the index recurrent VTE to death was 11.4 months (range, 0-83.9 months).

Conclusions: Cancer patients with recurrent VTE have a short median survival. Escalating the dose of LMWH can be effective for treating cases that are resistant to standard, weight-adjusted doses of LMWH or a VKA.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage
  • Anticoagulants / therapeutic use*
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Heparin, Low-Molecular-Weight / administration & dosage
  • Heparin, Low-Molecular-Weight / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Outcome Assessment, Health Care
  • Recurrence
  • Venous Thromboembolism / complications
  • Venous Thromboembolism / prevention & control*


  • Anticoagulants
  • Heparin, Low-Molecular-Weight