Prophylaxis and treatment of thromboembolism in oncology

Czech version

Authors: P. Kessler
Authors‘ workplace: Oddělení hematologie a transfuziologie Nemocnice Pelhřimov, p. o., přednosta prim. MUDr. Petr Kessler
Published in: Vnitř Lék 2009; 55(3): 219-222
Category: 15th Parizek's Days

Overview

In this article, following guidelines for clinical practice are formulated. 1. For patients undergoing cancer surgery, pharmacological thromboprophylaxis is recommended. Low molecular weight heparins (LMWH), unfractionated heparin (UFH) 5 000 U three times daily, or fondaparinux are recommended; in the Czech Republic, LMWH are most frequently used. For patients undergoing major cancer surgery extended prophylaxis for 4 weeks is recommended. For patients with a high risk of bleeding, intermittent pneumatic compression presents a reasonable alternative. 2. For cancer patients, who are bedridden, or hospitalized with an acute illness, thromboprophylaxis with LMWH is recommended. Patients with multiple myeloma, undergoing induction therapy, including at least 2 thrombogenic drugs (thalidomide, lenalidomide, dexamethasone, prednison, and anthracyclines) should be treated with LMWH. In other cancer patients, pharmacological thromboprophylaxis is not generally recommended, however, its application should be considered namely in patients with a history of venous thromboembolism (VTE), or in the presence of multiple risk factors. The cancer patients with VTE should be treated with LMWH for the first 6 months; the initial dose being 200 IU/kg daily, this can be reduced to 2/3–3/4 after one month. The therapy should be reevaluated after 6 month and subsequent therapy using LMWH or warfarin is recommended indefinitely, unless the cancer is resolved or any major contraindications arise.

Key words:
cancer – venous thromboembolism – LMWH – thromboprophylaxis – therapy

Sources

1. Blom JW, Doggen CJ, Osanto S et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293: 715–722.

2. Minnema MC, Fijnheer R, De Groot PG et al. Extremely high levels of von Willebrand factor antigen and of procoagulant factor VIII found in multiple myeloma patients are associated with activity status but not with thalidomide treatment. J Thromb Haemost 2003; 1: 445–449.

3. Ottinger H, Belka C, Kozole G et al. Deep venous thrombosis and pulmonary artery embolism in high‑grade non Hodgkin’s lymphoma: incidence, causes and prognostic relevance. Eur J Haematol 1995; 54: 186–194.

4. Auwerda JJ, Sonneveld P, de Maat MP et al. Prothrombotic coagulation abnormalities in patients with newly diagnosed multiple myeloma. Haematologica 2007; 92: 279–280.

5. Pritchard KI, Paterson AH, Paul NA 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. J Clin Oncol 1996; 14: 2731–2737.

6. Wun T, Law L, Harvey D et al. Increased incidence of symptomatic venous thrombosis in patients with cervical carcinoma treated with concurrent chemotherapy, radiation, and erythropoietin. Cancer 2003; 98: 1514–1520.

7. Duggan C, Marriott K, Edwards R et al. Inherited and acquired risk factors for venous thromboembolic disease among women taking tamoxifen to prevent breast cancer. J Clin Oncol 2003; 21: 3588–3593.

8. Blom JW, Vanderschoot JP, Oostindier MJ et al. Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: Results of a record linkage study. J Thromb Haemost 2006; 4: 529–535.

9. Rickles FR, Levine MN. Epidemiology of thrombosis in cancer. Acta Haematol 2001; 106: 6–12.

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

11. Mismetti P, Laporte S, Darmon JY et al. Meta‑analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg 2001; 88: 913–930.

12. Akl EA, Terrenato I, Barba M et al. Low-molecular-weight heparin vs unfractionated heparin for perioperative thromboprophylaxis in patients with cancer: a systematic review and meta‑analysis. Arch Intern Med 2008; 168: 1261–1269.

13. Simonneau G, Laporte S, Mismetti P et al. 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 2006; 4: 1693–1700.

14. von Tempelhoff GF, Harenberg J, Niemann F et al. 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 2000; 16: 815–824.

15. Maxwell GL, Synan I, Dodge R et al. Pneumatic compression versus low molecular weight heparin in gynecologic oncology surgery: a randomized trial. Obstet Gynecol 2001; 98: 989–995.

16. Agnelli G, Bergqvist D, Cohen AT et al. (PEGASUS investigators): Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high‑risk abdominal surgery. Br J Surg 2005; 92: 1212–1220.

17. Bergqvist D, Agnelli G, Cohen AT et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med 2002; 346: 975–980.

18. Geerts WH, Bergqvist D, Pineo GF et al. Prevention of Venous Thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th ed). Chest 2008; 133: 381–453.

19. Alikhan R, Cohen AT, Combe S et al. Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study. Blood Coagul Fibrinolysis 2003; 14: 341–346.

20. Elreda L, Vora RK, Cohen AJ. Standardized Thromboprophylaxis Increases Compliance and Reduces Venous Thrombotic Events (VTE) in Hospitalized Cancer Patients, abstract #3020, 50th ASH annual meeting, San Francisco, 6. 12.–9. 12. 2008.

21. Amin A, Hussein M, Battleman D et al. Appropriate VTE Prophylaxis Is Associated with Lower Direct Medical Costs among Medical and Surgical Patients in the United States. Abstract#1287, 50th ASH annual meeting, San Francisco, 6. 12.–9. 12. 2008.

22. Clahsen PC, van de Velde CJ, Julien JP et al. Thromboembolic complications after perioperative chemotherapy in women with early breast cancer: a European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group study. J Clin Oncol 1994; 12: 1266–1271.

23. Cuzick J, Forbes JF, Sestak I et al. Long‑term results of tamoxifen prophylaxis for breast cancer – 96-month follow‑up of the randomized IBIS-I trial. J Natl Cancer Inst 2007; 99: 272–282.

24. Khorana AA, Francis CW, Culakova E et al. Risk factors for chemotherapy‑associated venous thromboembolism in a prospective observational study. Cancer 2005; 104: 2822–2829.

25. Kessler P, Pour L, Gregora E et al. (Czech myeloma group): Low molecular weight heparins are effective and safe in thromboprophylaxis in newly diagnosed myeloma patients during the induction therapy (Abstract P-M-519). J Thromb Haemost 2007; 5 (Suppl 2): P-M-519.

26. Palumbo A, Bringhen S, Caravita T et al. Italian Multiple Myeloma Network, GIMEMA: Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 2006; 367: 825–831.

27. Kearon C, Kahn SR, Agnelli G et al. Antithrombotic Therapy for Venous Thromboembolic Disease. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th ed). Chest 2008; 133: 454–545.

28. Gould MK, Dembitzer AD, Doyle RL et al. Low-Molecular-Weight Heparins Compared with Unfractionated Heparin for Treatment of Acute Deep Venous Thrombosis. A Meta‑Analysis of Randomized, Controlled Trials. Ann Intern Med 1999; 130: 800–809.

29. Akl EA, Rohilla S, Barba M et al. Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev 2008; 1: CD006649.

30. Palareti G, Legnani C, Lee AYY 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. Thromb Haemost 2000; 84: 805–810.

31. Monreal M, Roncales FJ, Ruiz J et al. Secondary prevention of venous thromboembolism: A role for low-molecular-weight heparin. Haemostasis 1998; 28: 236–243.

32. Meyer G, Marjanovic Z, Valcke J 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. Arch Intern Med 2002; 162: 1729–1735.

33. Lee AYY, Levine MN, Baker RI et al.Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators: Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146–153.

34. Lee AYY, Rickles FR, Julian JA et al. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol 2005; 23: 2123–2129.

35. Hull RD, Pineo GF, Brant RF et al. LITE Trial Investigators: Long‑term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med 2006; 119: 1062–1072.

36. Akl EA, Barba M, Rohilla S et al. Anticoagulation for the long term treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev 2008; 2: CD006650.