Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Prophylactic and therapeutic anticoagulation for thrombosis—major issues in oncology

Nature Clinical Practice Oncology volume 6, pages 74–84 (2009)Cite this article

Abstract

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with cancer. Primary prevention with pharmacologic agents (or mechanical methods, if anticoagulants are contraindicated) is recommended in all cancer patients hospitalized for surgical or medical reasons. The role of prophylaxis in outpatients is less certain because of the diversity of the patient populations and their cancer treatments with respect to the associated risks of VTE and bleeding. Treatment with low-molecular weight heparin is the recommended first-line approach in cancer patients with newly diagnosed VTE, and is usually continued for a minimum of 3–6 months. Other management issues that require further research include the optimum duration of anticoagulant therapy, the treatment of recurrent VTE, the role of vena cava filters, the effects of VTE and its treatment on quality of life, and the impact of anticoagulants on survival. Newer anticoagulants hold promise in providing more-effective and convenient treatment of VTE in this high-risk population, but further studies are awaited.

Key Points

  • Primary prevention with pharmacologic agents (or mechanical methods, if anticoagulants are contraindicated) is recommended in all cancer patients hospitalized for surgery or medical reasons

  • Extending prophylaxis up to 30 days after surgery should be considered in patients with additional risk factors for venous thromboembolism (VTE)

  • Routine prophylaxis in outpatients is not recommended except in selected patients, such as those receiving thalidomide-based or lenalidomide-based therapy

  • Treatment with low-molecular-weight heparin is the recommended first-line approach in cancer patients with newly diagnosed VTE

  • Treatment duration should be individualized based on the stage or extent of the cancer, the risk of recurrent VTE, the risk of serious bleeding, the clinical status and personal preference of the patient

  • Evidence for the efficacy and safety of inferior vena cava filters is very limited and they should not be used in patients who can receive anticoagulants

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Khorana AA et al. (2007) Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 5: 632–634

    Article  CAS  PubMed  Google Scholar 

  2. Blom JW et al. (2005) Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 293: 715–722

    Article  CAS  PubMed  Google Scholar 

  3. Hutten BA et al. (2000) 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. J Clin Oncol 18: 3078–3083

    Article  CAS  PubMed  Google Scholar 

  4. Prandoni P et al. (2002) Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 100: 3484–3488

    Article  CAS  PubMed  Google Scholar 

  5. Elting LS et al. (2004) Outcomes and costs of deep venous thrombosis among patients with cancer. Arch Intern Med 164: 1653–1661

    Article  PubMed  Google Scholar 

  6. Geerts WH et al. (2004) Prevention of venous thromboembolism: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126: 338S–400S

    Article  CAS  PubMed  Google Scholar 

  7. Leonardi MJ et al. (2007) A systematic review of deep venous thrombosis prophylaxis in cancer patients: implications for improving quality. Ann Surg Oncol 14: 929–936

    Article  PubMed  Google Scholar 

  8. Fricker JP et al. (1988) Low dose heparin versus low molecular weight heparin (Kabi 2165, Fragmin) in the prophylaxis of thromboembolic complications of abdominal oncological surgery. Eur J Clin Invest 18: 561–567

    Article  CAS  PubMed  Google Scholar 

  9. McLeod RS et al. (2001) Subcutaneous heparin versus low molecular-weight heparin as thromboprophylaxis in patients undergoing colorectal surgery: results of the Canadian colorectal DVT prophylaxis trial: a randomized, double-blind trial. Ann Surg 233: 438–444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. ENOXACAN Study Group (1997) 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. Br J Surg 84: 1099–1103

  11. Petrov M et al. (2007) Enoxaparin versus heparin prophylaxis for venous thromboembolism after abdominal oncologic surgery: a randomized double-blind controlled trial [abstract #668]. J Thromb Haemost 5: 668

    Google Scholar 

  12. Bergqvist D et al. (2005) Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 5000 units in 2070 patients. Br J Surg 82: 496–501

    Article  Google Scholar 

  13. Balibrea JL et al. (2007) Bemiparin Cooperative Study Group in Surgery for Cancer. Optimal dosing of bemiparin as prophylaxis against venous thromboembolism in surgery for cancer: an audit of practice. Int J Surg 5: 114–119

    Article  CAS  PubMed  Google Scholar 

  14. Simonneau G et al. (2006) A randomized study comparing the efficacy and safety of nadroparin 2850 IU (0.3 mL) vs. enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism after colorectal surgery for cancer. J Thromb Haemost 4: 1693–1700

    Article  CAS  PubMed  Google Scholar 

  15. Bergqvist D et al. (2002) Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med 346: 975–980

    Article  CAS  PubMed  Google Scholar 

  16. Lausen I et al. (1998) Incidence and prevention of deep venous thrombosis occurring late after general surgery: randomized controlled study of prolonged thromboprophylaxis. Eur J Surg 164: 657–663

    Article  CAS  PubMed  Google Scholar 

  17. Rasmussen MS et al. (2003) Prolonged prophylaxis with low molecular weight heparin (Dalteparin) following major abdominal surgery for malignancy. Blood 102: 56a

    Google Scholar 

  18. Agnelli G et al. (2006) A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann Surg 243: 89–95

    Article  PubMed  PubMed Central  Google Scholar 

  19. Agnelli G et al. (2005) Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg 92: 1212–1220

    Article  CAS  PubMed  Google Scholar 

  20. Lyman GH et al. (2007) American society of clinical oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 25: 1–16

    Article  Google Scholar 

  21. Marras LC et al. (2000) The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review. Cancer 89: 640–646

    Article  CAS  PubMed  Google Scholar 

  22. Simanek R et al. (2007) Venous thromboembolism and survival in patients with high-grade glioma. Neuro-Oncology 9: 89–95

    Article  PubMed  PubMed Central  Google Scholar 

  23. Semrad TJ et al. (2007) Epidemiology of venous thromboembolism in 9489 patients with malignant glioma. J Neurosurg 106: 601–608

    Article  PubMed  Google Scholar 

  24. Cerrato D et al. (1978) Deep vein thrombosis and low-dose heparin prophylaxis in neurosurgical patients. J Neurosurg 49: 378–381

    Article  CAS  PubMed  Google Scholar 

  25. Melon E et al. (1987) Deep venous thrombosis prophylaxis by low molecular weight heparin in neurosurgical patients. Anesthesiology 75: A214

    Article  Google Scholar 

  26. Nurmohamed MT et al. (1996) Low molecular weight heparin and compression stockings in the prevention of venous thromboembolism in neurosurgery. Thromb Haemost 75: 233–238

    Article  CAS  PubMed  Google Scholar 

  27. Agnelli G et al. (1998) Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med 339: 80–85

    Article  CAS  PubMed  Google Scholar 

  28. Iorio A and Agnelli G (2000) Low-molecular-weight and unfractionated heparin for prevention of venous thromboembolism in neurosurgery: a meta-analysis. Arch Int Med 160: 2327–2332

    Article  CAS  Google Scholar 

  29. Dickinson LD et al. (1998) Enoxaparin increases the incidence of postoperative intracranial hemorrhage when initiated preoperatively for deep venous thrombosis prophylaxis in patients with brain tumors. Neurosurgery 43: 1074–1081

    Article  CAS  PubMed  Google Scholar 

  30. Goldhaber SZ et al. (2002) Low rate of venous thromboembolism after craniotomy for brain tumor using multimodality prophylaxis. Chest 122: 1933–1937

    Article  PubMed  Google Scholar 

  31. MacDonald RL et al. (2003) Randomized, pilot study of intermittent pneumatic compression devices plus dalteparin versus intermittent pneumatic compression devices plus heparin for prevention of venous thromboembolism in patients undergoing craniotomy. Surg Neurology 59: 363–372

    Google Scholar 

  32. Perry JR et al. (2007) PRODIGE: A phase III randomized placebo-controlled trial of thromboprophylaxis using dalteparin low molecular weight heparin (LMWH) in patients with newly diagnosed malignant glioma [abstract#2011]. J Clin Oncol 25 (Suppl): 77s

    Google Scholar 

  33. Clarke-Pearson DL et al. (1983) Venous thromboembolism prophylaxis in gynecologic oncology: a prospective, controlled trial of low-dose heparin. Am J Obst Gynecol 145: 606–613

    Article  CAS  Google Scholar 

  34. Clarke-Pearson DL et al. (1990) A controlled trial of two low-dose heparin regimens for the prevention of postoperative deep vein thrombosis. Obst Gynecol 75: 684–689

    Google Scholar 

  35. Einstein MH et al. (2007) Venous thromboembolism prevention in gynecologic cancer surgery: a systematic review. Gynecol Onc 105: 813–819

    Article  Google Scholar 

  36. Borstad E et al. (1988) Comparison of low molecular weight heparin vs unfractionated heparin in gynecological surgery. Acta Obstet Gynecol Scand 67: 99–103

    Article  CAS  PubMed  Google Scholar 

  37. Kaaja R et al. (1992) Comparison of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin, with or without dihydroergotamine, in abdominal hysterectomy. Eur J Obstet Gynecol Reprod Biol 47: 141–145

    Article  CAS  PubMed  Google Scholar 

  38. von Tempelhoff GF et al. (2000) Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: a prospective randomized double-blind trial. Int J Oncol 16: 815–824

    CAS  PubMed  Google Scholar 

  39. Baykal et al. (2001) Comparison of enoxaparin and standard heparin in gynaecologic oncologic surgery: a randomised prospective double-blind clinical study. Eur J Gynaecol Onc 22: 127–130

    CAS  Google Scholar 

  40. Cade JF et al. (1983) Prophylaxis of venous thrombosis after major thoracic surgery. ANZ J Surg 53: 301–304

    Article  CAS  Google Scholar 

  41. Azorin JF et al. (1997) Efficacy and tolerability of fraxiparine in the prevention of thromboembolic complications in oncologic thoracic surgery. Ann Cardiol Angeiol (Paris) 46: 341–347

    CAS  Google Scholar 

  42. Bigg SW et al. (1992) Prophylactic mini-dose heparin in patients undergoing radical retropubic prostatectomy. A prospective trial. Urology 39: 309–313

    Article  CAS  PubMed  Google Scholar 

  43. Sawczuk IS et al. (2002) Low molecular weight heparin for venous thromboembolism prophylaxis in urologic oncologic surgery. Cancer Invest 20: 889–892

    Article  CAS  PubMed  Google Scholar 

  44. Patiar S et al. (2007) Prevention of venous thromboembolism in surgical patients with breast cancer. Br J Surg 94: 412–420

    Article  CAS  PubMed  Google Scholar 

  45. Lin PP et al. (1998) Deep venous thrombosis after orthopedic surgery in adult cancer patients. J Surg Onc 68: 41–47

    Article  CAS  Google Scholar 

  46. Clarke-Pearson DL et al. (1984) Prevention of postoperative venous thromboembolism by external pneumatic calf compression in patients with gynecologic malignancy. Obstet Gynecol 63: 92–98

    CAS  PubMed  Google Scholar 

  47. Turpie AG et al. (1977) Prevention of venous thrombosis in patients with intracranial disease by intermittent pneumatic compression of the calf. Neurology 27: 435–438

    Article  CAS  PubMed  Google Scholar 

  48. Stein PD et al. (2006) Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med 1999: 60–68

    Article  Google Scholar 

  49. Khorana AA et al. (2006) Thromboembolism in hospitalized neutropenic cancer patients. J Clin Oncol 24: 484–490

    Article  PubMed  Google Scholar 

  50. Levine M et al. (1994) Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet 343: 886–889

    Article  CAS  PubMed  Google Scholar 

  51. Ciftci A et al. (2007) Thrombosis in patients with lung cancer and the effectiveness of low warfarin prophylaxis on patients survival [abstract #563]. J Thromb Haemost 5 (suppl 1): 563

    Google Scholar 

  52. Haas SK et al. (2005) Prevention of venous thromboembolism with low-molecular-weight heparin in patients with metastatic breast or lung cancer—results of the TOPIC Studies [abstract #OR059]. J Thromb Haemost 3 (Suppl 1): OR059

    Google Scholar 

  53. Pelzer H et al. (2007) Prospective, randomized open trial of enoxaparin in patient with advanced pancreatic cancer undergoing first-line chemotherapy [abstract #PT488]. J Thromb Haemost 5 (Suppl 2): PT488

    Google Scholar 

  54. Hirsh J (2007) Risk of thrombosis with lenalidomide and its prevention with aspirin. Chest 131: 275–277

    Article  CAS  PubMed  Google Scholar 

  55. Amin A et al. (2007) Thromboprophylaxis rates in US medical centers: success or failure? J Thromb Haemost 5: 1610–1616

    Article  CAS  PubMed  Google Scholar 

  56. Kucher et al. (2005) Electronic alerts to prevent venous thromboembolism among hospitalized patients. N Engl J Med 352: 969–971

    Article  CAS  PubMed  Google Scholar 

  57. Francis CW (2007) Prophylaxis for thromboembolism in hospitalized medical patients. N Engl Med 356: 1438–1444

    Article  CAS  Google Scholar 

  58. Van Dongen CJ et al.: Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD001100. 10.1002/14651858.CD001100.pub2

  59. Lee AYY (2003) Management of thrombosis in cancer: primary prevention and secondary prophylaxis. Br J Haematol 128: 291–302

    Article  Google Scholar 

  60. Ageno W et al. (2002) Selecting patients for home treatment of deep vein thrombosis: the problem of cancer. Haematologica 87: 286–291

    PubMed  Google Scholar 

  61. Martel N et al. (2005) Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood 106: 2710–2715

    Article  CAS  PubMed  Google Scholar 

  62. Lee AYY et al. (2003) Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349: 146–153

    Article  CAS  PubMed  Google Scholar 

  63. Hull RD et al. (2006) Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med 119: 1062–1072

    Article  CAS  PubMed  Google Scholar 

  64. Meyer G et al. (2002) Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Int Med 162: 1729–1735

    Article  CAS  Google Scholar 

  65. Deitcher SR et al. (2006) Secondary prevention of venous thromboembolic events in patients with active cancer: enoxaparin alone versus initial enoxaparin followed by warfarin for a 180-day period. Clin Applied Thromb Hemost 12: 389–396

    Article  CAS  Google Scholar 

  66. The van Gogh Investigators (2007) Idraparinux versus standard therapy for venous thromboembolic disease. N Engl J Med 357: 1094–1104

  67. The PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study (2005) Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism. Circulation 112: 416–422

  68. Buller HR et al. (2204) Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126 (3 Suppl): 401S–428S

    Google Scholar 

  69. Goerner A (1931) The influence of anticlotting agents on transplantation growth of tumor tissue. J Lab Clin Med 16: 369–372

    Google Scholar 

  70. Lebeau B et al. (1994) Subcutaneous heparin treatment increases survival in small cell lung cancer. “Petites Cellules” Group. Cancer 74: 38–45

    Article  CAS  PubMed  Google Scholar 

  71. Elias EG et al. (1975) Heparin and chemotherapy in the management of inoperable lung carcinoma. Cancer 36: 129–136

    Article  CAS  PubMed  Google Scholar 

  72. Zacharski LR et al. (1981) Effect of warfarin on survival in small cell carcinoma of the lung. Veterans Administration Study No. 75. JAMA 245: 831–835

    Article  CAS  PubMed  Google Scholar 

  73. Chahinian AP et al. (1989) A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B. J Clin Oncol 7: 993–1002

    Article  CAS  PubMed  Google Scholar 

  74. Altinbas M et al. (2004) A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer. J Thromb Haemost 2: 1266–1271

    Article  CAS  PubMed  Google Scholar 

  75. Klerk CPW et al. (2005) The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol 23: 2130–2135

    Article  CAS  PubMed  Google Scholar 

  76. Kakkar AK et al. (2004) Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). J Clin Oncol 22: 1944–1948

    Article  CAS  PubMed  Google Scholar 

  77. Sideras K et al. (2006) Low-molecular-weight-heparin in patients with advanced cancer: a phase 3 clinical trial. Mayo Clin Proc 81: 758–767

    Article  CAS  PubMed  Google Scholar 

  78. Zacharski LR et al. (1984) Effect of warfarin anticoagulation on survival in carcinoma of the lung colon, head and neck, and prostate. Final report of VA Cooperative Study 75. Cancer 53: 2046–2052

    Article  CAS  PubMed  Google Scholar 

  79. Maurer LH et al. (1997) 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. J Clin Oncol 15: 3378–3387

    Article  CAS  PubMed  Google Scholar 

  80. Lazo-Langner A et al. (2007) The effect of low-molecular-weight heparin on cancer survival. A systematic review and meta-analysis of randomized trials. J Thromb Haemost 5: 729–737

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. M Carrier is Assistant Professor at the Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.,

    Marc Carrier

  2. and Associate Professor at the Department of Medicine, AYY Lee is Director of Thrombosis, McMaster University, Hamilton, Ontario, Canada.,

    Agnes YY Lee

Authors
  1. Marc Carrier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Agnes YY Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Agnes YY Lee.

Ethics declarations

Competing interests

Agnes YY Lee declared that she receives research funding from Pfizer. Marc Carrier declared no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carrier, M., Lee, A. Prophylactic and therapeutic anticoagulation for thrombosis—major issues in oncology. Nat Rev Clin Oncol 6, 74–84 (2009). https://doi.org/10.1038/ncponc1244

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncponc1244

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing