Managing cancer-related venous thromboembolic disease: low-molecular-weight heparins and beyond

Venous thromboembolism is a major contributor to the morbidity and mortality of patients with cancer. For patients undergoing cancer surgery, several trials support the safety and efficacy of unfractionated heparin and of low-molecular-weight heparin for the prevention of venous thromboembolism, while data regarding the efficacy and safety of these agents in the setting of medical hospitalization is less definitive and must be extracted from trials including noncancer patients with different thrombotic risk factors. Randomized clinical studies confirm that patients with cancer who develop venous thromboembolism have superior outcomes when treated with long-term low-molecular-weight heparin as compared with warfarin. Novel anticoagulants that are orally bioavailable and function by directly inhibiting factor Xa or thrombin are entering the market. To date, data regarding the efficacy and safety of these novel anticoagulants as venous thromboembolism prophylaxis and treatment in cancer patients are not available and must be extracted from larger trials with heterogeneous patient populations.

[1]  Bengt I Eriksson,et al.  Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial , 2008, The Lancet.

[2]  G. Raskob,et al.  Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). , 2008, Chest.

[3]  B. Lobo,et al.  Fondaparinux for the treatment of patients with acute heparininduced thrombocytopenia , 2007, Thrombosis and Haemostasis.

[4]  Gary H Lyman,et al.  American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  H. Liebman,et al.  The role of oral anticoagulants in tumor biology. , 2007, Seminars in Thrombosis and Hemostasis.

[6]  G. Raskob,et al.  Idraparinux versus standard therapy for venous thromboembolic disease. , 2007, The New England journal of medicine.

[7]  E. Akl,et al.  Parenteral anticoagulation for prolonging survival in patients with cancer who have no other indication for anticoagulation. , 2007, The Cochrane database of systematic reviews.

[8]  Zhiwei Hu,et al.  Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms. , 2007, Blood.

[9]  S. Goldhaber,et al.  Thromboprophylaxis with dalteparin in medical patients: which patients benefit? , 2007, Vascular medicine.

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

[11]  C. Vigen,et al.  Unsuspected pulmonary emboli in cancer patients: clinical correlates and relevance. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  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.

[13]  C. Ettelaie,et al.  Tumour-expressed tissue factor inhibits cellular cytotoxicity , 2006, Cancer Immunology, Immunotherapy.

[14]  J. Rak,et al.  Tissue factor in cancer and angiogenesis: the molecular link between genetic tumor progression, tumor neovascularization, and cancer coagulopathy. , 2006, Seminars in thrombosis and hemostasis.

[15]  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.

[16]  M Gent,et al.  Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high‐risk abdominal surgery , 2005, The British journal of surgery.

[17]  A. Varki,et al.  Differential Metastasis Inhibition by Clinically Relevant Levels of Heparins—Correlation with Selectin Inhibition, Not Antithrombotic Activity , 2005, Clinical Cancer Research.

[18]  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.

[19]  C. Francis,et al.  Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial. , 2005, JAMA.

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

[21]  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.

[22]  G. Raskob,et al.  Fondaparinux or Enoxaparin for the Initial Treatment of Symptomatic Deep Venous Thrombosis , 2004, Annals of Internal Medicine.

[23]  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.

[24]  M Gent,et al.  Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. , 2003, The New England journal of medicine.

[25]  J. Degen,et al.  Mechanisms Linking Hemostatic Factors to Tumor Growth in Mice , 2003, Pathophysiology of Haemostasis and Thrombosis.

[26]  M. Prins,et al.  Secondary prophylaxis with warfarin for venous thromboembolism. , 2003, The New England journal of medicine.

[27]  M. Prins,et al.  Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. , 2003, The New England journal of medicine.

[28]  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.

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

[30]  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.

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

[32]  S. Laporte,et al.  Meta‐analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery , 2001, The British journal of surgery.

[33]  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.

[34]  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.

[35]  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.

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

[37]  T. Hastie,et al.  Low-Molecular-Weight Heparins Compared with Unfractionated Heparin for Treatment of Acute Deep Venous Thrombosis , 1999, Annals of Internal Medicine.

[38]  D. Bergqvist,et al.  Bowel ischaemia after aortoiliac surgery , 1997, The British journal of surgery.

[39]  W. Konigsberg,et al.  Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

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

[41]  V. Kakkar,et al.  Low molecular weight versus standard heparin for prevention of venous thromboembolism after major abdominal surgery , 1993, The Lancet.

[42]  I. Fidler,et al.  Inhibition of murine melanoma experimental metastasis by recombinant desulfatohirudin, a highly specific thrombin inhibitor. , 1991, Cancer research.

[43]  J. Degen,et al.  Mechanisms linking tumor cell-associated procoagulant function to tumor metastasis. , 2007, Thrombosis research.

[44]  A. Varki,et al.  Heparin attenuates metastasis mainly due to inhibition of P- and L-selectin, but non-anticoagulant heparins can have additional effects. , 2007, Thrombosis research.

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

[46]  lexander,et al.  Duration of Prophylaxis against Venous Thromboembolism with Enoxaparin after Surgery for Cancer , 2002 .

[47]  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 .