American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer.

PURPOSE To develop guideline recommendations for the use of anticoagulation in the prevention and treatment of venous thromboembolism (VTE) in patients with cancer. METHODS A comprehensive systematic review of the medical literature on the prevention and treatment of VTE in cancer patients was conducted and reviewed by a panel of content and methodology experts. Following discussion of the results, the panel drafted recommendations for the use of anticoagulation in patients with malignant disease. RESULTS The results of randomized controlled trials of primary and secondary VTE medical prophylaxis, surgical prophylaxis, VTE treatment, and the impact of anticoagulation on survival of patients with cancer were reviewed. Recommendations were developed on the prevention of VTE in hospitalized, ambulatory, and surgical cancer patients as well as patients with established VTE, and for use of anticoagulants in cancer patients without VTE to improve survival. CONCLUSION Recommendations of the American Society of Clinical Oncology VTE Guideline Panel include (1) all hospitalized cancer patients should be considered for VTE prophylaxis with anticoagulants in the absence of bleeding or other contraindications; (2) routine prophylaxis of ambulatory cancer patients with anticoagulation is not recommended, with the exception of patients receiving thalidomide or lenalidomide; (3) patients undergoing major surgery for malignant disease should be considered for pharmacologic thromboprophylaxis; (4) low molecular weight heparin represents the preferred agent for both the initial and continuing treatment of cancer patients with established VTE; and (5) the impact of anticoagulants on cancer patient survival requires additional study and cannot be recommended at present.

[1]  J. Rigas,et al.  Secondary prevention of venous thromboembolic events (VTE) in patients with active malignancy: a randomized study of enoxaparin sodium alone vs. initial enoxaparin sodium followed by warfarin for a 180-day period , 2003 .

[2]  H. Chew,et al.  Incidence of venous thromboembolism and its effect on survival among patients with common cancers. , 2006, Archives of internal medicine.

[3]  H. Chew,et al.  Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  Giancarlo Agnelli,et al.  Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. , 2004, Chest.

[5]  A. Nicolaides,et al.  Deep vein thrombosis of the leg. Is there a "high risk" group? , 1970, American journal of surgery.

[6]  N. Akar,et al.  Prevalence of Factor V 1691 G–A (Leiden) and prothrombin G20210A polymorphisms and the risk of venous thrombosis among cancer patients , 2007, Journal of Thrombosis and Thrombolysis.

[7]  P. Novotny,et al.  Low-Molecular-Weight Heparin in Patients With Advanced Cancer: A Phase 3 Clinical Trial , 2006 .

[8]  A. Unal,et al.  A randomized clinical trial of combination chemotherapy with and without low‐molecular‐weight heparin in small cell lung cancer , 2004, Journal of thrombosis and haemostasis : JTH.

[9]  J. Ragaz,et al.  Dose density by any other name. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  M. Monreal,et al.  Venous thromboembolism in very elderly patients: findings from a prospective registry (RIETE). , 2006, Haematologica.

[11]  G. Schwarzer,et al.  Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. , 2006, Journal of the National Cancer Institute.

[12]  M. Gould,et al.  Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials. , 1999, Annals of internal medicine.

[13]  D. Bergqvist Risk of venous thromboembolism in patients undergoing cancer surgery and options for thromboprophylaxis , 2007, Journal of surgical oncology.

[14]  M. Cushman,et al.  Factor V Leiden, prothrombin 20210A and the risk of venous thrombosis among cancer patients , 2005, British journal of haematology.

[15]  Susanne M. Smorenburg,et al.  The effect of low molecular weight heparin on survival in patients with advanced malignancy. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Ma Dong,et al.  Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer , 2006 .

[17]  M. Prins,et al.  Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  P Kelly Marcom,et al.  Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  M. Levine,et al.  Low-molecular-weight heparin vs. a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer☆ , 2003 .

[20]  W M O'Fallon,et al.  Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. , 2000, Archives of internal medicine.

[21]  S. Deitcher,et al.  Diagnosis of venous thromboembolic disease in cancer patients. , 2003, Oncology.

[22]  M. Levine,et al.  Incidence, risk factors, and outcomes of catheter-related thrombosis in adult patients with cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  A. Iorio,et al.  Low-Molecular-Weight Heparin and Cancer Survival: Review of the Literature and Pooled Analysis of 1,726 Patients Treated for at Least Three Months , 2003, Pathophysiology of Haemostasis and Thrombosis.

[24]  H. Büller,et al.  The Effects of Vitamin K-antagonists on Survival of Patients with Malignancy: A Systematic Analysis , 2001, Thrombosis and Haemostasis.

[25]  D. Bergqvist,et al.  Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 5000 XaI units in 2070 patients , 1995, The British journal of surgery.

[26]  Jeffrey S. Ginsberg,et al.  Treatment of Deep-Vein Thrombosis , 2004 .

[27]  K. L. Lewis,et al.  Multidetector Computed Tomography for Acute Pulmonary Embolism , 2007 .

[28]  N. Nguyen,et al.  Venous Thrombosis in Patients with Solid Tumors: Determination of Frequency and Characteristics , 2002, Thrombosis and Haemostasis.

[29]  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.

[30]  A R Jadad,et al.  Assessing the quality of randomized controlled trials: an annotated bibliography of scales and checklists. , 1995, Controlled clinical trials.

[31]  E. Altschuler,et al.  The risk and efficacy of anticoagulant therapy in the treatment of thromboembolic complications in patients with primary malignant brain tumors. , 1990, Neurosurgery.

[32]  P Prandoni,et al.  Venous thromboembolism and cancer: guidelines of the Italian Association of Medical Oncology (AIOM). , 2006, Critical reviews in oncology/hematology.

[33]  P. Wille-Jørgensen,et al.  Heparins and mechanical methods for thromboprophylaxis in colorectal surgery. , 2004, The Cochrane database of systematic reviews.

[34]  B. Zee,et al.  Increased thromboembolic complications with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer. National Cancer Institute of Canada Clinical Trials Group Breast Cancer Site Group. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  A. Khorana,et al.  Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy , 2007, Journal of thrombosis and haemostasis : JTH.

[36]  L. Jørgensen,et al.  Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open‐label study , 2006, Journal of thrombosis and haemostasis : JTH.

[37]  B. Guillonneau,et al.  Multi-institutional study of symptomatic deep venous thrombosis and pulmonary embolism in prostate cancer patients undergoing laparoscopic or robot-assisted laparoscopic radical prostatectomy. , 2008, European urology.

[38]  P. Vineis,et al.  Quality of systematic reviews used in guidelines for oncology practice. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[39]  F. Parazzini,et al.  A Clinical Outcome-Based Prospective Study on Venous Thromboembolism After Cancer Surgery: The @RISTOS Project , 2006, Annals of surgery.

[40]  T. Barbui,et al.  Incidence of thrombotic complications in patients with haematological malignancies with central venous catheters: a prospective multicentre study , 2005, British journal of haematology.

[41]  S. Singletary,et al.  Incidence and Prevention of Venous Thromboembolism in Patients Undergoing Breast Cancer Surgery and Treated According to Clinical Pathways , 2006, Annals of surgery.

[42]  R. Dodge,et al.  Venous thromboembolism prophylaxis: patients at high risk to fail intermittent pneumatic compression. , 2003 .

[43]  J. Olsen,et al.  Prognosis of cancers associated with venous thromboembolism. , 2000, The New England journal of medicine.

[44]  J. Hirsh,et al.  Management of anticoagulation before and after elective surgery. , 1997, The New England journal of medicine.

[45]  M. Levine,et al.  Do Heparins Do More than Just Treat Thrombosis? The Influence of Heparins on Cancer Spread , 1999, Thrombosis and Haemostasis.

[46]  R. Dodge,et al.  Pneumatic Compression Versus Low Molecular Weight Heparin in Gynecologic Oncology Surgery: A Randomized Trial , 2001, Obstetrics and gynecology.

[47]  A. Encke,et al.  Evaluation of perioperative fatal pulmonary embolism and death in cancer surgical patients , 2005, Thrombosis and Haemostasis.

[48]  A. Iorio,et al.  Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. , 1998, The New England journal of medicine.

[49]  J. Zeldis,et al.  Lenalidomide and venous thrombosis in multiple myeloma. , 2006, The New England journal of medicine.

[50]  PREVENTION OF FATAL POSTOPERATIVE PULMONARY EMBOLISM BY LOW DOSES OF HEPARIN An International Multicentre Trial , 1975, The Lancet.

[51]  B. Modan,et al.  Reduction of mortality in general medical in-patients by low-dose heparin prophylaxis. , 1982, Annals of internal medicine.

[52]  L. Fielding,et al.  Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for colorectal adenocarcinoma , 1992, The Lancet.

[53]  Robert J Cersosimo,et al.  Tamoxifen for Prevention of Breast Cancer , 2003 .

[54]  F. Rosendaal,et al.  Incidence of venous thrombosis in a large cohort of 66 329 cancer patients: results of a record linkage study , 2006, Journal of thrombosis and haemostasis : JTH.

[55]  V. Levin,et al.  Risk of intracranial hemorrhage in glioma patients receiving anticoagulant therapy for venous thromboembolism. , 1987, Journal of neurosurgery.

[56]  Paolo Prandoni,et al.  Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. , 2002, Blood.

[57]  G. Raskob,et al.  Self-managed long-term low-molecular-weight heparin therapy: the balance of benefits and harms. , 2007, The American journal of medicine.

[58]  S. Cohn,et al.  Randomized clinical trial of intermittent pneumatic compression and low molecular weight heparin in trauma , 2003, The British journal of surgery.

[59]  Jeffrey S. Ginsberg,et al.  Clinical practice. Treatment of deep-vein thrombosis. , 2004, The New England journal of medicine.

[60]  C K Redmond,et al.  Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. , 1999, Journal of the National Cancer Institute.

[61]  A. Folsom,et al.  Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE). , 2002, The American journal of medicine.

[62]  B. Barlogie,et al.  Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. , 2001, Blood.

[63]  R. Hull,et al.  Antithrombotic therapy for venous thromboembolic disease. , 1986, Chest.

[64]  S. Goldhaber,et al.  Randomized, Placebo-Controlled Trial of Dalteparin for the Prevention of Venous Thromboembolism in Acutely Ill Medical Patients , 2004, Circulation.

[65]  S SEVITT,et al.  Prevention of venous thrombosis and pulmonary embolism in injured patients. A trial of anticoagulant prophylaxis with phenindione in middle-aged and elderly patients with fractured necks of femur. , 1959, Lancet.

[66]  A. Turpie,et al.  A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. , 1999, The New England journal of medicine.

[67]  M. Engelhard,et al.  Deep venous thrombosis and pulmonary artery embolism in high‐grade non Hodgkin's lymphoma: incidence, causes and prognostic relevance , 1995, European journal of haematology.

[68]  Susanne M. Smorenburg,et al.  The Effects of Unfractionated Heparin on Survival in Patients with Malignancy – A Systematic Review , 1999, Thrombosis and Haemostasis.

[69]  A. Turpie,et al.  Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study , 2003, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[70]  A. Khorana,et al.  A meta‐analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment , 2007, Cancer.

[71]  A. Khorana,et al.  Risk factors for chemotherapy‐associated venous thromboembolism in a prospective observational study , 2005, Cancer.

[72]  S. Rajkumar,et al.  Thalidomide therapy and deep venous thrombosis in multiple myeloma. , 2005, Mayo Clinic proceedings.

[73]  C. Ko,et al.  A Systematic Review of Deep Venous Thrombosis Prophylaxis in Cancer Patients: Implications for Improving Quality , 2007, Annals of Surgical Oncology.

[74]  M. Shah,et al.  Thromboembolic events in gastric cancer: high incidence in patients receiving irinotecan- and bevacizumab-based therapy. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[75]  Yves Gruel,et al.  Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. , 2002, Archives of internal medicine.

[76]  Jawed Fareed,et al.  Secondary Prevention of Venous Thromboembolic Events in Patients With Active Cancer: Enoxaparin Alone Versus Initial Enoxaparin Followed by Warfarin for a 180-Day Period , 2006, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[77]  B. Gårdlund,et al.  Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases , 1996, The Lancet.

[78]  Michael Thomas,et al.  Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

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

[80]  R. Coleman,et al.  Prevention of Postoperative Venous Thromboembolism by External Pneumatic Calf Compression in Patients With Gynecologic Malignancy , 1984, Obstetrics and gynecology.

[81]  M. Prins,et al.  Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial , 2006, BMJ : British Medical Journal.

[82]  J. Olin,et al.  Treatment of Deep Vein Thrombosis and Pulmonary Emboli in Patients With Primary and Metastatic Brain Tumors Anticoagulants or Inferior Vena Cava Filter , 1987 .

[83]  K. Propert,et al.  A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B. , 1989, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[84]  P. Wen,et al.  Complications of therapy for venous thromboembolic disease in patients with brain tumors , 1993, Neurology.

[85]  P. Stein,et al.  Incidence of venous thromboembolism in patients hospitalized with cancer. , 2006, The American journal of medicine.

[86]  J. Hirsh,et al.  Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. , 1996, The American journal of medicine.

[87]  C. Colwell,et al.  Prevention of venous thromboembolism. , 1994, Chest.

[88]  L. Bressollette Eight-Year Follow-Up of Patients With Permanent Vena Cava Filters in the Prevention of Pulmonary Embolism: The PREPIC (Prévention du Risque d’Embolie Pulmonaire par Interruption Cave) Randomized Study , 2005, Circulation.

[89]  M. Cucherat,et al.  Prevention of Venous Thromboembolism in Internal Medicine with Unfractionated or Low-molecular-weight Heparins: A Meta-analysis of Randomised Clinical Trials , 2000, Thrombosis and Haemostasis.

[90]  M. Rasmussen Preventing thromboembolic complications in cancer patients after surgery: a role for prolonged thromboprophylaxis. , 2002, Cancer treatment reviews.

[91]  J. Massey,et al.  Low-dose heparin prophylaxis against fatal pulmonary embolism. , 1975, British medical journal.

[92]  A. Encke,et al.  Comparison of a low molecular weight heparin and unfractionated heparin for the prevention of deep vein thrombosis in patients undergoing abdominal surgery , 1988, The British journal of surgery.

[93]  R. Gray,et al.  Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[94]  E. Weiderpass,et al.  Venous thromboembolism and cancer , 1998, The Lancet.

[95]  A. Nicolaides,et al.  Deep vein thrombosis of the leg , 1970 .

[96]  J. Herndon,et al.  Randomized trial of chemotherapy and radiation therapy with or without warfarin for limited-stage small-cell lung cancer: a Cancer and Leukemia Group B study. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[97]  E. Lemarié,et al.  Subcutaneous heparin treatment increases survival in small cell lung cancer , 1994, Cancer.

[98]  D. Bergqvist Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessme , 1997 .

[99]  J. Garber,et al.  Effect of Factor V Leiden and prothrombin G20210-->A mutations on thromboembolic risk in the national surgical adjuvant breast and bowel project breast cancer prevention trial. , 2006, Journal of the National Cancer Institute.

[100]  R. Wolff,et al.  Venous thrombosis in cancer patients: insights from the FRONTLINE survey. , 2003, The oncologist.

[101]  J. Hirsh,et al.  Double-blind randomised trial of very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer , 1994, The Lancet.

[102]  A. Gallus Prevention of Post-operative Deep Leg Vein Thrombosis in Patients with Cancer , 1997, Thrombosis and Haemostasis.

[103]  B. Gärdlund Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases. The Heparin Prophylaxis Study Group. , 1996, Lancet.

[104]  J. Berkhof,et al.  Potential role of platelets in endothelial damage observed during treatment with cisplatin, gemcitabine, and the angiogenesis inhibitor SU5416. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[105]  D. Lamping,et al.  An evaluation of the costs, effectiveness and quality of renal replacement therapy provision in renal satellite units in England and Wales. , 2005, Health technology assessment.

[106]  Marilyn D Paterno,et al.  Electronic alerts to prevent venous thromboembolism among hospitalized patients. , 2005, The New England journal of medicine.

[107]  Huey-Dong Wu,et al.  Ultrasonographic evaluation of liver/spleen movements and extubation outcome. , 2004, Chest.

[108]  Miriam Lopez Gomez,et al.  Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients , 2008, Cancer.

[109]  L. Melton,et al.  Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. , 2002, Archives of internal medicine.

[110]  W. Henderson,et al.  Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate: Final Report of VA cooperative study # 75 , 1984, Cancer.

[111]  F. Rosendaal,et al.  The Effects of a Smoking Cessation Intervention on 14.5-Year Mortality , 2005, Annals of Internal Medicine.

[112]  John Crowley,et al.  Thrombotic complications in patients with newly diagnosed multiple myeloma treated with lenalidomide and dexamethasone: benefit of aspirin prophylaxis. , 2006, Blood.

[113]  S Seeber,et al.  Risk factors for venous thromboembolic events in cancer patients. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[114]  F. Rosendaal,et al.  Risk factors for catheter-related thrombosis in cancer patients. , 2004, European journal of cancer.

[115]  G. Guyatt,et al.  Applying the grades of recommendation for antithrombotic and thrombolytic therapy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. , 2004, Chest.

[116]  R. Collins,et al.  Reduction in Fatal Pulmonary Embolism and Venous Thrombosis by Perioperative Administration of Subcutaneous Heparin: Overview of Results of Randomized Trials in General, Orthopedic, and Urologic Surgery , 1989 .

[117]  T. Barbui,et al.  Thrombosis in Cancer Patients Treated with Hematopoietic Growth Factors - A Meta-Analysis , 1996, Thrombosis and Haemostasis.

[118]  David M Jablons,et al.  Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[119]  Rafael Fonseca,et al.  Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[120]  G. Guyatt,et al.  The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy , 2004 .

[121]  D. Clarke‐Pearson Prevention of venous thromboembolism in gynecologic surgery patients , 1993, Current opinion in obstetrics & gynecology.

[122]  R. Coleman,et al.  A randomized trial of low-dose heparin and intermittent pneumatic calf compression for the prevention of deep venous thrombosis after gynecologic oncology surgery. , 1993, American journal of obstetrics and gynecology.

[123]  H. Rauschecker,et al.  Final results of a phase III clinical trial on adjuvant intraportal infusion with heparin and 5-fluorouracil (5-FU) in resectable colon cancer (EORTC GITCCG 1983-1987). European Organization for Research and Treatment of Cancer. Gastrointestinal Tract Cancer Cooperative Group. , 1997, European journal of cancer.

[124]  Joan S. Reisch,et al.  Prevention of Venous Thromboembolism in General Surgical Patients: Results of Meta‐analysis , 1988, Annals of surgery.

[125]  R. J. Tuttle,et al.  Prevention of venous thrombosis with small, subcutaneous doses of heparin. , 1976, JAMA.

[126]  M. Baccarani,et al.  Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy. , 2002, Blood.

[127]  F. Kabbinavar,et al.  Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[128]  R. Ruff,et al.  Incidence and treatment of peripheral venous thrombosis in patients with glioma , 1983, Annals of neurology.

[129]  K. Dickersin,et al.  Systematic Reviews: Identifying relevant studies for systematic reviews , 1994 .

[130]  Clifford W Colwell,et al.  Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. , 2004, Chest.

[131]  R. Fisher,et al.  Thromboembolism in hospitalized neutropenic cancer patients. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[132]  P. Richardson,et al.  Thalidomide- and lenalidomide-associated thromboembolism among patients with cancer. , 2006, JAMA.

[133]  G. Lip,et al.  The hypercoagulable state of malignancy: pathogenesis and current debate. , 2002, Neoplasia.

[134]  Robert A Kyle,et al.  Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. , 2005, Blood.

[135]  Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment. ENOXACAN Study Group. , 1997, The British journal of surgery.

[136]  Joseph A. Smith,et al.  Malignancies, prothrombotic mutations, and the risk of venous thrombosis. , 2005, The Journal of urology.

[137]  O. Huber,et al.  Postoperative pulmonary embolism after hospital discharge. An underestimated risk. , 1992, Archives of surgery.

[138]  S. Goldhaber,et al.  Mortality rates and risk factors for asymptomatic deep vein thrombosis in medical patients , 2004, Thrombosis and Haemostasis.

[139]  A A Rimm,et al.  Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. , 1999, Medicine.

[140]  Russell D Hull,et al.  Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. , 2006, The American journal of medicine.

[141]  M. Clarke,et al.  Identifying relevant studies for systematic reviews , 1995, BMJ.

[142]  A. Cohen,et al.  Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. , 2002, The New England journal of medicine.

[143]  L. Deangelis,et al.  Therapy of venous thromboembolism in patients with brain metastases , 1994, Cancer.

[144]  L. Elting,et al.  Outcomes and cost of deep venous thrombosis among patients with cancer , 2004 .

[145]  R. Williamson,et al.  Thromboprophylaxis in malignant disease , 1995, British Journal of Surgery.

[146]  A. Turpie,et al.  Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX Study. , 2004, Archives of internal medicine.

[147]  J. Douketis,et al.  A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency. , 2000, Archives of internal medicine.

[148]  W. Beattie,et al.  Prevention of venous thrombosis in patients with intracranial disease by intermittent pneumatic compression of the calf , 1977, Neurology.

[149]  W M O'Fallon,et al.  Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. , 1998, Archives of internal medicine.