Elsevier

The Lancet Oncology

Volume 9, Issue 6, June 2008, Pages 577-584
The Lancet Oncology

Review
Management of venous thromboembolism in patients with advanced cancer: a systematic review and meta-analysis

https://doi.org/10.1016/S1470-2045(08)70149-9Get rights and content

Summary

Venous thromboembolism is common in patients with cancer. However, no management guidelines exist for venous thromboembolism specific to patients with advanced progressive cancer. To help develop recommendations for practice, we have done a comprehensive review of anticoagulation treatment in patients with cancer, with particular focus on studies that included patients with advanced disease. Data from 19 publications, including randomised, prospective, and retrospective studies suggest that: long-term full-dose low-molecular-weight heparin (LMWH) is more effective than warfarin in the secondary prophylaxis of venous thromboembolism in patients with cancer of any stage, performance status, or prognosis; warfarin should not be used in patients with advancing progressive disease; and in patients at high risk of bleeding, full-dose LMWH for 7 days followed by a long-term decreased fixed dose long term can be considered. The optimum treatment duration is unclear, but because the prothrombotic tendency will persist in patients with advanced cancer, indefinite treatment is generally recommended. For patients with contraindications to anticoagulation, inferior-vena-caval filters can be considered, but their use needs careful patient selection. Ultimately, the decision to initiate, continue, and stop anticoagulation will need to be made on an individual basis, guided by the available evidence, the patient's circumstances, and their informed preferences.

Introduction

The association between venous thromboembolism and cancer is well recognised.1 A prothrombotic state is present in many cancers as a result of an increase in procoagulants, such as tissue factor, cancer procoagulant, and factor VIIa, and hypercoaguability increases as the cancer progresses.2, 3, 4 Up to 15% of patients with cancer develop symptomatic venous thromboembolism (figure 1) that needs anticoagulation, and these patients have a poorer prognosis than those without venous thromboembolism; only 12% of patients with cancer and venous thromboembolism survive beyond 1 year.5, 6, 7 The prevalence of asymptomatic venous thromboembolism seems to increase with cancer progression. Asymptomatic deep-vein thrombosis can be present in half of hospice inpatients,8 and pulmonary embolism is noted in 30–50% of patients with cancer at post mortem.9, 10

Venous thromboembolism is generally treated by anticoagulation, initially with low-molecular-weight heparin (LMWH) followed by vitamin K antagonists, such as warfarin, for 3–6 months.11 The aim of this treatment is to prevent propagation of the existing deep-vein thrombosis and secondary prevention of further venous thromboembolism. However, compared with the general medical population, the treatment of venous thromboembolism in patients with cancer is more challenging, especially in advanced disease. An increased risk of recurrent thrombosis or bleeding while on warfarin has been extensively documented in patients with cancer.12, 13, 14, 15, 16, 17 Recent studies have consequently looked at the LMWHs as alternative long-term anticoagulants in this setting.18, 19, 20, 21 Current clinical guidelines consequently recommend LMWH for the long-term treatment of cancer-related venous thromboembolism in preference to warfarin.22, 23, 24, 25 However, such recommendations do not seem to be based on a formal systematic review and meta-analysis of the published work. Furthermore, many studies have investigated the management of venous thromboembolism in the general cancer population, involving patients who are receiving active treatment; therefore, their findings might not be fully transferable to patients within the palliative-care setting.

To help develop practice guidelines applicable to patients with advanced cancer across the entire spectrum of performance status and prognosis, the Thrombosis Taskgroup of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland has done this systematic review. The search for evidence was expanded beyond randomised controlled trials, and the data were pooled for meta-analysis where possible.

Section snippets

Methods

We searched Medline, The Cochrane Library, Embase, CINAHL, the British Nursing Index, AMED, Web of Science, and SCOPUS for papers published between January, 1966, and December, 2006, by use of the search terms “neoplasms”, “palliative care”, “thromboembolism”, and “anticoagulants”. There were no language or location restrictions. A hand search was done of the journals Palliative Medicine, Progress in Palliative Care, Journal of Pain and Symptom Management, and Journal of Supportive Oncology for

Results

Our search identified 5884 references. Only studies that reported anticoagulant treatment in patients with advanced cancer, and provided sufficient data on study design, participants and outcomes, were selected for closer reading. Two reviewers (SIRN and MJJ) independently selected 35 papers for review.12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52 Of these papers, six were excluded because the study

Discussion

Increasing treatment options and better supportive care are leading to improved survival for patients with cancer, However, this increased survival means that the management of venous thromboembolism in patients with cancer is likely to be a frequent challenge for physicians Patients with advancing metastatic cancer are at the greatest risk of venous thromboembolism and, when receiving anticoagulation treatment, these patients have a high risk of recurrent venous thromboembolism and bleeding

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