Der Internist

, Volume 55, Issue 4, pp 448–454 | Cite as

Prophylaxe und Therapie venöser Thromboembolien bei Tumorerkrankungen

Stellenwert niedermolekularer Heparine
Arzneimitteltherapie
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Zusammenfassung

Tumorpatienten haben ein erhöhtes Risiko für venöse Thromboembolien (VTE). Niedermolekulare Heparine (NMH) werden aufgrund ihrer raschen und zuverlässigen Wirksamkeit zur Prophylaxe und Therapie von VTE bei Tumorpatienten bevorzugt eingesetzt. Während die Prophylaxe perioperativ sowie bei stationären Tumorpatienten unter Berücksichtigung bestehender Kontraindikationen etabliert ist, wird sie bei ambulanten Tumorpatienten nicht generell empfohlen. In der Initialtherapie und Sekundärprävention von akuten VTE sind NMH effektiver als unfraktionierte Heparine und Vitamin-K-Antagonisten. Die Sekundärprophylaxe mit NMH sollte zunächst für 3–6 Monate durchgeführt und bei fortbestehendem Tumorleiden und niedrigem Blutungsrisiko weitergeführt werden. Der Einsatz der neuen direkten oralen Antikoagulanzien (DOAC) kann bei Tumorpatienten aufgrund fehlender Studiendaten gegenwärtig nicht empfohlen werden.

Schlüsselwörter

Vitamin-K-Antagonisten Unfraktioniertes Heparin Antikoagulanzien Perioperative Prophylaxe Sekundärprävention 

Prophylaxis and treatment of venous thromboembolism in cancer patients

Clinical value of low-molecular-weight heparins

Abstract

Venous thromboembolism (VTE) is a common complication in patients with cancer. Because of their improved subcutaneous bioavailability and reliable antithrombotic efficiency low-molecular-weight heparins (LMWH) are preferably used for prevention and treatment of cancer-related VTE. Thromboprophylaxis with LMWH is well established in patients undergoing cancer surgery and hospitalized cancer patients, while outpatient prophylaxis remains contentious. LMWH are recommended over unfractionated heparins and vitamin K antagonists for initial treatment and secondary prophylaxis (3–6 months) after cancer-related VTE. Long-term secondary prophylaxis should be considered for patients with ongoing active malignancy and low bleeding risk. Due to absence of clinical studies in cancer patients, the use of novel oral anticoagulants is currently not recommended.

Keywords

Vitamin K antagonists Unfractionated heparin Anticoagulants Perioperative prophylaxis Secondary prevention 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt. S. Kreher gibt an, dass kein Interessenkonflikt besteht. H. Riess ist in den vergangenen 5 Jahren beratend für Pharmaunternehmen tätig gewesen, die antithrombotische oder gerinnungshemmende Substanzen entwickeln oder vertreiben. Dies betrifft: Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, LEO Pharma, Novartis, Pfizer und Sanofi. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften. S3-Leitlinie: Prophylaxe der venösen Thromboembolie (VTE). Stand: 1. Mai 2010Google Scholar
  2. 2.
    Agnelli G, Bergqvist D, Cohen AT 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 92:1212–1220PubMedCrossRefGoogle Scholar
  3. 3.
    Agnelli G, George DJ, Kakkar AK et al (2012) Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 366:601–609Google Scholar
  4. 4.
    Agnelli G, Gussoni G, Bianchini C et al (2009) 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 10:943–949PubMedCrossRefGoogle Scholar
  5. 5.
    Akl EA, Labedi N, Barba M et al (2011) Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev:CD006650Google Scholar
  6. 6.
    Akl EA, Labedi N, Terrenato I et al (2011) Low molecular weight heparin versus unfractionated heparin for perioperative thromboprophylaxis in patients with cancer. Cochrane Database Syst Rev:CD009447Google Scholar
  7. 7.
    Akl EA, Vasireddi SR, Gunukula S et al (2011) Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev:CD006649Google Scholar
  8. 8.
    Barsam SJ, Patel R, Arya R (2013) Anticoagulation for prevention and treatment of cancer-related venous thromboembolism. Br J Haematol 161:764–777PubMedCrossRefGoogle Scholar
  9. 9.
    Bergqvist D, Agnelli G, Cohen AT et al (2002) Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med 346:975–980Google Scholar
  10. 10.
    Blom JW, Vanderschoot JP, Oostindier MJ et al (2006) Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J Thromb Haemost 4:529–535Google Scholar
  11. 11.
    Cohen AT, Spiro TE, Buller HR et al (2013) Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 368:513–523Google Scholar
  12. 12.
    Deitcher SR, Kessler CM, Merli G 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 Appl Thromb Hemost 12:389–396PubMedCrossRefGoogle Scholar
  13. 13.
    Di Nisio M, Porreca E, Ferrante N et al (2012) Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev:CD008500Google Scholar
  14. 14.
    Goldhaber SZ, Leizorovicz A, Kakkar AK et al (2011) Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 365:2167–2177Google Scholar
  15. 15.
    Guyatt GH, Akl EA, Crowther M et al (2012) Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 Suppl):7S–47SPubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Horsted F, West J, Grainge MJ (2012) Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 9:e1001275PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Hull RD, Pineo GF, Brant RF et al (2006) Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med 119:1062–1072PubMedCrossRefGoogle Scholar
  18. 18.
    Kakkar AK (2009) Prevention of venous thromboembolism in the cancer surgical patient. J Clin Oncol 27:4881–4884Google Scholar
  19. 19.
    Kakkar AK, Williamson RC (1999) Prevention of venous thromboembolism in cancer patients. Semin Thromb Hemost 25:239–243PubMedCrossRefGoogle Scholar
  20. 20.
    Kanaan AO, Silva MA, Donovan JL et al (2007) Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients. Clin Ther 29:2395–2405PubMedCrossRefGoogle Scholar
  21. 21.
    Khorana AA, Kuderer NM, Culakova E et al (2008) Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 111:4902–4907PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Laporte S, Bertoletti L, Romera A et al (2012) Long-term treatment of venous thromboembolism with tinzaparin compared to vitamin K antagonists: a meta-analysis of 5 randomized trials in non-cancer and cancer patients. Thromb Res 130:853–858PubMedCrossRefGoogle Scholar
  23. 23.
    Lee AY, Levine MN, Baker RI 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 349:146–153Google Scholar
  24. 24.
    Lee AY, Rickles FR, Julian JA et al (2005) Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol 23:2123–2129Google Scholar
  25. 25.
    Meyer G, Marjanovic Z, Valcke J 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 Intern Med 162:1729–1735PubMedCrossRefGoogle Scholar
  26. 26.
    Mismetti P, Laporte S, Darmon JY et al (2001) Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg 88:913–930PubMedCrossRefGoogle Scholar
  27. 27.
    Palareti G, Legnani C, Lee A et al (2000) A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy. Thromb Haemost 84:805–810PubMedGoogle Scholar
  28. 28.
    Prandoni P, Lensing AW, Piccioli A et al (2002) Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 100:3484–3488PubMedCrossRefGoogle Scholar
  29. 29.
    Rasmussen MS, Jorgensen LN, Wille-Jorgensen P et al (2006) Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study. J Thromb Haemost 4:2384–2390Google Scholar
  30. 30.
    Riess H, Haas S, Tebbe U et al (2010) A randomized, double-blind study of certoparin vs. unfractionated heparin to prevent venous thromboembolic events in acutely ill, non-surgical patients: CERTIFY Study. J Thromb Haemost 8:1209–1215Google Scholar
  31. 31.
    Riess H, Pelzer U, Opitz B et al (2010) A prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy: final results of the CONKO-004 trial. ASCO Annual Meeting Abstract #4033Google Scholar
  32. 32.
    Simonneau G, Laporte S, Mismetti P 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 4:1693–1700Google Scholar
  33. 33.
    Thaler J, Ay C, Pabinger I (2012) Venous thromboembolism in cancer patients – risk scores and recent randomised controlled trials. Thromb Haemost 108:1042–1048PubMedCrossRefGoogle Scholar
  34. 34.
    Timp JF, Braekkan SK, Versteeg HH et al (2013) Epidemiology of cancer-associated venous thrombosis. Blood 122:1712–1723PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und TumorimmunologieCharité – Universitätsmedizin Berlin, Campus Benjamin FranklinBerlinDeutschland

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