Cancer and venous thromboembolism

doi:10.1016/S1470-2045(05)70207-2

The Lancet Oncology

Volume 6, Issue 6, June 2005, Pages 401-410

https://doi.org/10.1016/S1470-2045(05)70207-2 Get rights and content

Summary

Venous thromboembolism occurs commonly in patients with cancer. The pathogenetic mechanisms of thrombosis involve a complex interaction between tumour cells, the haemostatic system, and characteristics of the patient. Among risk factors for thromboembolism are long-term immobilisation, especially in hospital, surgery, and chemotherapy with or without adjuvant hormone therapy. Although prophylaxis and treatment of thromboembolism in patients with cancer draw on the agents that are commonly used in those without cancer, there are many special features of patients with cancer that make use of these drugs more challenging. Low-molecular-weight heparins are the cornerstone of prophylaxis and treatment of venous thromboembolism in patients with cancer. These drugs have the potential to increase survival, at least in patients with more favourable outlook. About 10% of patients with idiopathic venous thromboembolism have an underlying malignant disorder that can be detected by extensive diagnostic investigation. However, the issue of whether screening for occult malignant disease ultimately improves prognosis and survival remains to be resolved.

Introduction

Thromboembolism is a well-recognised complication of malignant disease. Clinical manifestations vary from venous thromboembolism to disseminated intravascular coagulation and arterial embolism. Disseminated intravascular coagulation is most commonly observed in patients with haematological malignant disorders and those with widespread metastatic cancer, whereas arterial embolism is most commonly observed in patients undergoing chemotherapy and in those with non-bacterial thrombotic endocarditis. This review focuses on the relation between cancer and venous thromboembolism.

Section snippets

Pathogenesis of thrombosis in cancer

Cancer growth is associated with the development of a hypercoaguable state. Patients with malignant disorders but no thrombosis commonly present with abnormalities in laboratory coagulation tests, which suggest a continuous process of fibrin formation and removal at different rates in these patients.¹ Fibrin and other clot components have roles not only in thrombogenesis but also in tumour adhesion (figure 1), spread, and metastasis.² Many histopathological studies have shown the presence of

Prothrombotic mechanisms

The activation of blood coagulation in patients with cancer is complex and multifactorial.⁴ General prothrombotic mechanisms are related to the host response to cancer and include the acute-phase reaction, paraprotein production, inflammation, necrosis, and haemodynamic disorders. Procoagulant effects are also exerted by anticancer chemotherapy and radiotherapy. However, a prominent part is played by tumour-specific clot-promoting mechanisms resulting from the prothrombotic properties expressed

Prothrombotic mechanisms and tumour progression

Tumour-specific prothrombotic properties contribute to the process of tumour growth and dissemination. The formation of thrombin, the final effector enzyme of the clotting cascade, and production of fibrin, the final product of the activation of blood coagulation, are coagulation-dependent mechanisms of tumour progression. In addition, tumour prothrombotic properties can interfere with the malignant process by coagulation-independent mechanisms (figure 4). Relevant in this setting is the

Epidemiology and risk factors for thromboembolism in patients with cancer

Since the initial observation by Trousseau in 1865, many studies have addressed the relation between cancer and venous thromboembolism. This disorder is a common complication in patients with cancer. In some cases it is the first manifestation of cancer, so offering opportunities for diagnosis and treatment.¹⁵ In patients with malignant disorders, venous thromboembolism is an important cause of morbidity and mortality. Of every seven patients with cancer who die in hospital, one dies of

Thromboprophylaxis

Although many patients with active cancer develop thrombotic complications spontaneously, in the absence of other risk factors, there is probably little point in providing thromboprophylaxis to all patients with cancer who are not undergoing surgical or medical therapy. However, a history of thromboembolism puts patients with cancer at such a high risk of recurrence that the systematic use of mechanical or pharmacological prophylaxis should be considered even in the absence of the common risk

Initial treatment

Except for selected patients who need aggressive treatments, most patients with cancer and thromboembolism should receive subcutaneous injections of therapeutic doses (adjusted to bodyweight) of LMWH once or twice daily. Alternatively, a course of full-dose unfractionated heparin that lengthens the activated partial thromboplastin time ratio to 1·5–3·0 can be used.⁴⁹ Whenever possible, LMWH or unfractionated heparin should be given as soon as there is a reasonable possibility that venous

Effect of antithrombotic drugs on cancer

Anticoagulant treatment of patients with cancer, particularly lung cancer, has been reported to improve survival.⁵⁵ These preliminary results of controlled trials lent some support to the idea that activation of blood coagulation has a role in the natural history of tumour growth.⁵⁶

Many studies have compared LMWH with standard heparin in the treatment of venous thromboembolism, and an updated meta-analysis of the most adequate reports was published in 2000.⁵⁷ In eight of nine studies reporting

Risk of cancer in patients with venous thromboembolism

The strong association between cancer and venous thromboembolism is further emphasised by the high frequency of cancer detection or development in patients with thromboembolism.

In patients presenting with venous thromboembolism, the frequency of cancer not known previously and discovered by routine investigation (ie, history taking, physical examination, urine analysis, routine blood tests, and chest radiography) varies substantially between studies. The variation is related to the extent of

Search strategy and selection criteria

Data for this review were identified by searches of MEDLINE, Current Contents, PubMed, and references from relevant articles with the search terms “venous thrombosis”, “venous thromboembolism”, “pulmonary embolism”, “anticoagulation”, “risk factors”, “cancer”, “thrombophilia”, “heparin”, and “warfarin”. Abstracts and reports from meetings were included only when they related directly to previously published work. Only papers published in English between 1980 and 2005 were included.

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