Vol 12, No 4 (2016)
Review paper
Published online: 2016-12-22
Page views 846
Article views/downloads 2384
Get Citation

Connect on Social Media

Connect on Social Media

Nadroparin in the prophylaxis and treatment of thromboembolic complications in cancer patients

Marek Z. Wojtukiewicz, Piotr Skalij, Piotr Tokajuk
DOI: 10.5603/OCP.2016.0001
Oncol Clin Pract 2016;12(4):119-127.

Abstract

Thromboembolic events are the most frequent complications and second leading cause of death among cancer patients. The most common forms include deep venous thrombosis of lower extremities and pulmonary embolism. The risk of thrombosis is correlated with underlying, patient’s clinical characteristic, functions of coagulation system as well as anticancer treatment. There is a well-established evidence for using of antithrombotic prophylaxis in cancer patients undergoing surgery and hospitalised due to different causes. There are some scores, based on laboratory and clinical factors, that facilitate qualification to the prophylaxis (e.g. Caprini score, Padua Prediction Score). The role of low-molecular-weight heparins (LMWH) in prophylaxis of thrombosis in cancer patients was established based on the results of many randomised clinical trials. Currently, the use this group of drugs — both in the treatment and in prophylaxis of venous thromboembolism (VTE) — is a part of standard of care. Nadroparin is one of the LMWHs with well-documented efficacy and safety in cancer patients.

Article available in PDF format

Purchase Subscription

References

  1. Lee AYY. Thrombosis in cancer: an update on prevention, treatment, and survival benefits of anticoagulants. Hematology Am Soc Hematol Educ Program. 2010; 2010: 144–149.
  2. Wojtukiewicz MZ, Sierko E. Zakrzepy a nowotwory. In: Windyga J, Pasierski T, Torbicki A. ed. Zakrzepy i zatory. Ed. 3. Wydawnictwo Lekarskie PZWL, Warszawa 2014: 85–106.
  3. Levitan N, Dowlati A, Remick S, et al. Rates of Initial and Recurrent Thromboembolic Disease Among Patients with Malignancy Versus Those without Malignancy: Risk Analysis Using Medicare Claims Data. Medicine. 1999; 78(5): 285–91.
  4. Prandoni P. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002; 100(10): 3484–3488.
  5. Khorana AA. Cancer and thrombosis: implications of published guidelines for clinical practice. Ann Oncol. 2009; 20(10): 1619–1630.
  6. Wojtukiewicz MZ, Sierko E. Zaburzenia hemostazy u chorych na nowotwory. In: Krzakowski M. ed. Onkologia kliniczna. Ed. 2, ext. Wydawnictwo Medyczne BORGIS, Warszawa 2006: 444–476.
  7. Franco AT, Corken A, Ware J. Platelets at the interface of thrombosis, inflammation, and cancer. Blood. 2015; 126(5): 582–588.
  8. Lima LG, Monteiro RQ. Activation of blood coagulation in cancer: implications for tumour progression. Biosci Rep. 2013; 33(5).
  9. Wojtukiewicz MZ, Sierko E. Zaburzenia hemostazy u chorych na nowotwory. In: Jeziorski A, Szawłowski AW, Towpik E. ed. Chirurgia onkologiczna. Ed. 1. Wydawnictwo Lekarskie PZWL, Warszawa 2009: 185–204.
  10. Blom JW, Doggen CJM, Osanto S, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005; 293(6): 715–722.
  11. Danilenko-Dixon DR, Heit JA, Silverstein MD, et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med. 2000; 160(6): 809–815.
  12. Nalluri SR, Chu D, Keresztes R, et al. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA. 2008; 300(19): 2277–2285.
  13. Bennett CL, Silver SM, Djulbegovic B, et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA. 2008; 299(8): 914–924.
  14. Haddad TC, Greeno EW. Chemotherapy-induced thrombosis. Thromb Res. 2006; 118(5): 555–568.
  15. Lee AYY, Kamphuisen PW. Epidemiology and prevention of catheter-related thrombosis in patients with cancer. J Thromb Haemost. 2012; 10(8): 1491–1499.
  16. Khorana AA. Cancer-associated thrombosis: updates and controversies. Hematology Am Soc Hematol Educ Program. 2012; 2012: 626–630.
  17. Windyga J. Powikłania zakrzepowo-zatorowe w chorobie nowotworowej — zasady postępowania w Instytucie Hematologii i Transfuzjologii. Hematologia. 2013; 1: 56–64.
  18. Bergqvist D, Agnelli G, Cohen AT, et al. ENOXACAN II Investigators. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med. 2002; 346(13): 975–980.
  19. Rasmussen MS, Jorgensen LN, Wille-Jørgensen PW. Prolonged thromboprophylaxis with low molecular weight heparin (dalteparin) after major abdominal surgery: the FAME study. J Thromb Haemost. 2003; 1(suppl 1): abstract OC399.
  20. Encke A, Breddin K. Comparison of a low molecular weight heparin and unfractionated heparin for the prevention of deep vein thrombosis in patients undergoing abdominal surgery. British Journal of Surgery. 1988; 75(11): 1058–1063.
  21. Pezzuoli G, Neri Serneri GG, Settembrini PG, et al. Prophylaxis of fatal pulmonary embolism in general surgery using low-molecular weight heparin Cy 216: a multicentre, double-blind, randomized, controlled, clinical trial versus placebo (STEP). STEP-Study Group. Int Surg. 1989; 74(4): 205–210.
  22. Simonneau G, Laporte S, Mismetti P, et al. FX140 Study Investigators. 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(8): 1693–1700.
  23. 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(7): 913–930.
  24. Azorin JF, Regnard JF, Dahan M, et al. [Efficacy and tolerability of fraxiparine in the prevention of thromboembolic complications in oncologic thoracic surgery]. Ann Cardiol Angeiol (Paris). 1997; 46(5-6): 341–347.
  25. Wojtukiewicz MZ, Sierko E, Tomkowski W, et al. Wytyczne dotyczące profilaktyki i leczenia żylnej choroby zakrzepowo-zatorowej u chorych na nowotwory poddawanych leczeniu zachowawczemu. Onkol Prakt Klin Edu. 2016; 2: 73–101.
  26. Farge D, Bounameaux H, Brenner B, et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost. 2013; 11(1): 56–70.
  27. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008; 111(10): 4902–4907.
  28. Lyman GH, Bohlke K, Khorana AA, et al. American Society of Clinical Oncology, American Society of Clinical Oncology Clinical Practice, American Society of Clinical Oncology. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol. 2007; 25(34): 5490–5505.
  29. Klerk CPW, Smorenburg SM, Otten HM, et al. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol. 2005; 23(10): 2130–2135.
  30. Agnelli G, Gussoni G, Bianchini C, et al. PROTECHT Investigators. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol. 2009; 10(10): 943–949.
  31. Verso M, Agnelli G, Barni S, et al. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score. Intern Emerg Med. 2012; 7(3): 291–292.
  32. Zawilska K, Bała M, Błędowski DW, et al. Polskie wytyczne profilaktyki i leczenia żylnej choroby zakrzepowo-zatorowej — aktualizacja 2012. Med Prakt. 2012; 5: 9–19.
  33. Leizorovicz A, Siguret V, Mottier D, et al. Innohep® in Renal Insufficiency Study Steering Committee. Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: the Innohep® in Renal Insufficiency Study (IRIS). Thromb Res. 2011; 128(1): 27–34.
  34. 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(2): 146–153.
  35. 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(15): 1729–1735.
  36. 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(12): 1062–1072.
  37. Prandoni P, Lensing AW, Büller HR, et al. Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet. 1992; 339(8791): 441–445.
  38. Dolovich LR, Ginsberg JS, Douketis JD, 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. Arch Intern Med. 2000; 160(2): 181–188.
  39. Mandalà M, Falanga A, Roila F, et al. ESMO Guidelines Working Group. Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2011; 22 Suppl 6: vi85–vi92.
  40. Deitcher SR, Kessler CM, Merli G, et al. ONCENOX Investigators. 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 Appl Thromb Hemost. 2006; 12(4): 389–396.
  41. López-Beret P, Orgaz A, Fontcuberta J, et al. Low molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous thrombosis. J Vasc Surg. 2001; 33(1): 77–90.
  42. Billon N, Gloaguen F, Funck-Brentano C, et al. Clinical evaluation of pain during subcutaneous injections of low molecular weight heparins in healthy volunteers. Br J Clin Pharmacol. 1994; 37(4): 395–397.
  43. Piovella F, Barone M. Clinical experience of nadroparin in patients with cancer. European Oncology. 2008; 4: 34–40.