Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis.

A small proportion of patients with deep vein thrombosis develop recurrent venous thromboembolic complications or bleeding during anticoagulant treatment. These complications may occur more frequently if these patients have concomitant cancer. This prospective follow-up study sought to determine whether in thrombosis patients those with cancer have a higher risk for recurrent venous thromboembolism or bleeding during anticoagulant treatment than those without cancer. Of the 842 included patients, 181 had known cancer at entry. The 12-month cumulative incidence of recurrent thromboembolism in cancer patients was 20.7% (95% CI, 15.6%-25.8%) versus 6.8% (95% CI, 3.9%- 9.7%) in patients without cancer, for a hazard ratio of 3.2 (95% CI, 1.9-5.4) The 12-month cumulative incidence of major bleeding was 12.4% (95% CI, 6.5%-18.2%) in patients with cancer and 4.9% (95% CI, 2.5%-7.4%) in patients without cancer, for a hazard ratio of 2.2 (95% CI, 1.2-4.1). Recurrence and bleeding were both related to cancer severity and occurred predominantly during the first month of anticoagulant therapy but could not be explained by sub- or overanticoagulation. Cancer patients with venous thrombosis are more likely to develop recurrent thromboembolic complications and major bleeding during anticoagulant treatment than those without malignancy. These risks correlate with the extent of cancer. Possibilities for improvement using the current paradigms of anticoagulation seem limited and new treatment strategies should be developed.

[1]  Vittorio Pengo,et al.  Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT) , 1996, The Lancet.

[2]  H. Büller,et al.  Diagnosis of recurrent deep vein thrombosis. , 1995, Haemostasis.

[3]  Edward Pan,et al.  Glioblastoma Multiforme and Anaplastic Astrocytoma , 2003 .

[4]  W. Henderson,et al.  Bleeding complications from warfarin anticoagulation in patients with malignancy. , 1987, Journal of medicine.

[5]  Jeffrey S. Ginsberg,et al.  Management of venous thromboembolism. , 1996, The New England journal of medicine.

[6]  G. Hughes,et al.  The management of thrombosis in the antiphospholipid-antibody syndrome. , 1995, The New England journal of medicine.

[7]  Paolo Prandoni,et al.  The Long-Term Clinical Course of Acute Deep Venous Thrombosis , 1996, Annals of Internal Medicine.

[8]  J. Levin,et al.  Trousseau's syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. , 1977 .

[9]  N. Callander,et al.  Trousseau's syndrome. , 1993, The Western journal of medicine.

[10]  H. Büller,et al.  Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis , 1992, The Lancet.

[11]  J. Hirsh,et al.  Diagnosis of pulmonary embolism. , 2003, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[12]  A. Alavi,et al.  The clinical course of pulmonary embolism. , 1992, The New England journal of medicine.

[13]  M. Prins,et al.  Risk for subsequent venous thromboembolic complications in carriers of the prothrombin or the factor V gene mutationRisk for subsequent venous thromboembolic complications in carriers of the prothrombin or the factor V gene mutation with a first episode of deep-vein thrombosis , 2000 .

[14]  F. Barral,et al.  A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. , 1998, The New England journal of medicine.

[15]  F. Rickles,et al.  Activation of blood coagulation in cancer: Trousseau's syndrome revisited. , 1983, Blood.

[16]  J. Levin,et al.  Trousseau's syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. , 1977, Medicine.

[17]  G. Raskob,et al.  A cost-effectiveness analysis of alternative approaches for long-term treatment of proximal venous thrombosis. , 1984, JAMA.

[18]  J. Vandenbroucke,et al.  Bleeding Complications in Oral Anticoagulant Therapy , 1993 .

[19]  J. Hirsh,et al.  A Comparison of the Safety and Efficacy of Oral Antiocoagulation for the Treatment of Venous Thromboembolic Disease in Patients with or without Malignancy , 2000, Thrombosis and Haemostasis.

[20]  S. Green,et al.  Glioblastoma multiforme and anaplastic astrocytoma pathologic criteria and prognostic implications , 1985, Cancer.

[21]  M. Baccarani,et al.  Staging and prognosis in chronic myelogenous leukemia. , 1988, Seminars in hematology.

[22]  J. Vandenbroucke,et al.  Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. , 1993, Archives of internal medicine.

[23]  B. Gersh,et al.  Bleeding and thromboembolism during anticoagulant therapy: a population-based study in Rochester, Minnesota. , 1995, Mayo Clinic proceedings.

[24]  S. Salmon,et al.  A clinical staging system for multiple myeloma correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival , 1975, Cancer.

[25]  M Gent,et al.  Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  M H Prins,et al.  Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy. , 2000, Archives of internal medicine.

[27]  M. Prins,et al.  Deep-vein thrombosis , 1999, The Lancet.

[28]  Emili Montserrat,et al.  A predictive model for aggressive non-Hodgkin's lymphoma. , 1993, The New England journal of medicine.

[29]  M. Prins,et al.  Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. , 1997, The New England journal of medicine.

[30]  Mark J. Thomas,et al.  A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis , 1981, Cancer.

[31]  Marcel Levi,et al.  Disseminated Intravascular Coagulation , 1999 .

[32]  D M Wallace,et al.  The Efficacy and Safety of Oral Anticoagulation in Patients with Cancer , 1995, Thrombosis and Haemostasis.

[33]  M. Prins,et al.  Deep-vein thrombosis and the incidence of subsequent symptomatic cancer. , 1992, The New England journal of medicine.

[34]  P. Prandoni,et al.  Noninvasive objective tests for the diagnosis of clinically suspected deep-vein thrombosis. , 1995, Haemostasis.

[35]  P. Bossuyt,et al.  Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. , 1996, The New England journal of medicine.