Phlebologie 2011; 40(05): 251-256
DOI: 10.1055/s-0037-1621779
Übersichtsarbeit
Schattauer GmbH

Tumor – Chemotherapie – Thrombose

Von der Virchowschen Trias zur Onkologischen Therapie-TriasFrom Virchow's Triad to the Oncology Therapy Triad
A. Matzdorff
1   Klinik f. Hämatologie und Onkologie, Caritasklinik St. Theresia Saarbrücken
› Author Affiliations
Further Information

Publication History

Received:04 July 2011

Accepted:23 August 2011

Publication Date:
30 December 2017 (online)

Zusammenfassung

Thromboembolien sind keine seltene Komplikation bei der Behandlung von Tumoren. Zahlreiche Mechanismen verknüpfen Tumorwachstum und Gerinnungsaktivierung. Dazu kommen die thrombosefördernde Wirkung bestimmter Tumorwirkstoffe, das zunehmende Alter der Patienten und deren längeres Überleben. Allen stationären Tumorpatienten sollte eine Thromboseprophylaxe angeboten werden. Bei ambulanten Patienten, die eine tumorspezifische Therapie erhalten, ist der Nutzen einer Thromboseprophylaxe bisher nicht sicher belegt. Bei ambulanten Myelom-Patienten, die IMiDe (Immune Modulatory Drugs; Thalidomid, Revlimid) erhalten und bei Pankreaskarzinom-Patienten mit Chemotherapie wird jedoch eine Thromboseprophylaxe empfohlen. Wenn eine Thromboembolie eingetreten ist gibt man bei Tumorpatienten ein niedermolekulares Heparin in therapeutischer Dosis (Näheres siehe Fachinformation) und solange die Tumorerkrankung aktiv ist, z.T. bis an das Lebensende des Patienten.

Summary

Venous thromboembolism is not an uncommon complication of cancer therapy. Numerous mechanisms link tumor growth with the activation of clotting factors. Increasing age of patients, longer survival, and prothrombogenic effects of anti-cancer drugs add to this risk. All oncology inpatients should be offered thromboprophylaxis. In outpatients the benefit of thromboprophylaxis is still under discussion. Ambulatory myeloma patients with IMiD-therapy (thalidomide, revlimide) and patients with pancreatic carcinoma should be offered prophylactic heparin. The standard treatment of established venous thromboembolism in cancer patients is therapeutic-dose low molecular weight heparin (see specific product informations) as long as the cancer is active, sometimes until the end of life.

 
  • Literatur

  • 1 Virchow R. Thrombose und Embolie. In: Gesammelte Abhandlungen zur Wissenschaftlichen Medicin. Frankfurt: Meidinger Sohn & Co; 1856
  • 2 Ferlay J, Shin HR, Bray F. et al. GLOBO CAN 2008 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010
  • 3 The ATAC Trialists’ Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002; 359: 2131-2139.
  • 4 Look M, van Putten W, Duffy M. et al. Pooled analysis of prognostic impact of uPA and PAI-1 in breast cancer patients. Thromb Haemost 2003; 91: 538-548.
  • 5 Erpenbeck L, Schön M. Deadly allies: the fatal interplay between platelets and metastasizing cancer cells. Blood 2010; 115: 3427-3436.
  • 6 Kucher N, Spirk D, Baumgartner I. et al. Lack of prophylaxis before the onset of acute venous thromboembolism among hospitalized cancer patients: the SWIss Venous ThromboEmbolism Registry (SWIVTER). Ann Oncol 2010; 21: 931-935.
  • 7 Rickles FR, Edwards RL. Activation of blood coagulation in cancer: Trousseau’s syndrome revisited. Blood 1983; 62: 14-31.
  • 8 Paneesha S, McManus A, Arya R. et al. Frequency, demographics and risk (according to tumour type or site) of cancer-associated thrombosis among patients seen at outpatient DVT clinics. Thromb Haemost 2010; 103: 338-343.
  • 9 Khorana AA, Kuderer NM, Culakova E. et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111: 4902-4907.
  • 10 Labianca R, Gsparini G, Barni S. et al. Prediction of venous thromboembolism in ambulatory patients with cancer receiving chemotherapy: An expanded thromboembolic risk score model. J Clin Oncol 2011; 29 Suppl; Abstr #e19551
  • 11 Ay C, Dunkler D, Marosi C. et al. Prediction of venous thromboembolism in cancer patients. Blood 2010; 116: 5377-5382.
  • 12 Sud R, Khorana AA. Cancer-associated thrombosis: risk factors, candidate biomarkers and a risk model. Thromb Res 2009; 123 Suppl (Suppl. 04) S18-21.
  • 13 Kosmas T, Kallistratos MS. et al. Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study. J Cancer Res Clin Oncol 2008; 134: 75-82.
  • 14 Scappaticci FA, Skillings JR. et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 2007; 99: 1232-1239.
  • 15 Lechner D, Weltermann A. Pathophysiologie der Chemotherapie-assoziierten Thrombose. Hämostaseologie 2008; 28: 112-120.
  • 16 Haddad TC, Greeno EW. Chemotherapy-induced thrombosis. Thromb Res 2006; 118: 555-568.
  • 17 AWMF: S3-Leitlinie Prophylaxe der venösen Thromboembolie (VTE) Version vom 18. März 2009 mit eingearbeitetem Addendum vom 8. Mai. 2010 www.awmf.org
  • 18 Mandala M, Falanga A, Roila F. on behalf of the ESMO Guidelines Working Group. Management of venous thromboembolism in cancer patients: ESMO Clinical Recommendations. Ann Oncol 009 20 Suppl (04) iv182-iv184.
  • 19 Lyman GH, Khorana AA, Falanga A. et al. American Society of Clinical Oncology Guideline: Recommendations for Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer. J Clin Oncol 2007; 25: 5490-5505.
  • 20 Agnelli G, Gussoni G, Bianchini C. et al. 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: 943-949.
  • 21 Agnelli G, George DJ, Fisher W. et al. The ultra-low molecular weight heparin (ULMWH) semuloparin for prevention of venous thromboembolism (VTE) in patients with cancer receiving chemotherapy: SAVE ONCO study. J Clin Oncol 2011; 29 (Suppl., Part II of II) 496s, abstr.#LBA9014
  • 22 Palumbo A, Cavo M, Bringhen S. et al. Aspirin, Warfarin, or Enoxaparin Thromboprophylaxis in Patients With Multiple Myeloma Treated With Thalidomide: A Phase III, Open-Label, Randomized Trial. J Clin Oncol 2011; 29: 986-993.
  • 23 Pelzer U, Deutschinoff G, Opitz B. et al. The impact of low molecular weight heparin in first-line pancreatic cancer treatment – final results of the CONKO 004 trial. Onkologie 2010; 33 Suppl (Suppl. 06) 200 Abstr. #P668
  • 24 Bergqvist D, Agnelli G, Cohen AT. et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer (ENOXACAN II Study). New Engl J Med 2002; 346: 975-980.
  • 25 Rasmussen MS, Jorgensen LN, Wille-Jorgensen P. et al. Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study (FAME Study). J Thromb Haemost 2006; 4: 2384-2390.
  • 26 Jorgensen LN, Lausen I, Rasmussen MS. et al. Prolonged thromboprophylaxis with low molecular weight heparin (tinzaparin) following major general surgery primarily for cancer: An individual patient data metaanalysis. J Thromb Haemost 2003; 1 Suppl (Suppl. 01) P1870
  • 27 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; Apr 16 (02) CD006650
  • 28 Prandoni P, Lensing AWA, Piccioli A. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100: 3484-3488.
  • 29 Van Doormaal FF, Raskob GE, Davidson BL. et al. Treatment of venous thromboembolism in patients with cancer: Subgroup analysis of the Matisse clinical trials. Thromb Haemost 2009; 101: 762-769.
  • 30 Khorana AA, Streiff MB, Farge D. et al. A Consensus Statement of Major Guidelines Panels and Call to Action. J Clin Oncol 2009; 27: 4919-4926.
  • 31 Lee AYY, Levine MN, Baker RI. et al. for the 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.
  • 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. Arch Intern Med 2002; 162: 1729-1735.
  • 33 Deitcher SR, Kessler CM, Merli G. et al. Secondary prevention of venous thromboembolic events in patients with active cancer: enoxaparin alone versus initial enoxaparin followed by warfarin for a 180-day period. Clinical and Applied Thrombosis/ Hemostasis 2006; 12: 389-396.
  • 34 Hull RD, Pineo GF, Brant RF. et al. for the 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.
  • 35 Kakkar AK, Kadziola Z, Williamson RCN. et al. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). J Clin Oncol 2004; 22: 1944-1948.
  • 36 Gasic GJ, Gasic TB, Murophy S. Anti-metastatic effect of aspirin. Lancet 1972; 2 07783 932-933.
  • 37 Van Doormaal FF, Di Nisio M, Otten HM. et al. Randomized Trial of the Effect of the Low Molecular Weight Heparin Nadroparin on Survival in Patients With Cancer. J Clin Oncol 2011; 29: 2071-2076.
  • 38 Mousa SA, Petersen JL. Anti-cancer properties of low-molecular-weight heparin: Preclinical evidence. Thromb Haemost 2009; 102: 258-267.
  • 39 Kakkar AK, Levine M, Pinedo HM. et al. Venous thrombosis in cancer patients: insights from the FRONTLINE survey. Oncologist 2003; 8: 381-388.
  • 40 Kalka C, Spirk D, Siebenroch KA. et al. Lack of extended venous thromboembolism prophylaxis in high-risk patients undergoing major orthopaedic or major cancer surgery. Electronic Assessment of VTE Prophylaxis in High-Risk Surgical Patients at Discharge from Swiss Hospitals (ESSENTIAL). Thromb Haemost 2009; 102: 56-61.
  • 41 Wittkowsky AK. Barriers to the long-term use of low-molecular weight heparins for treatment of cancer-associated thrombosis. J Thromb Haemost 2006; 4: 2090-2091.
  • 42 Khorana AA. Cancer and thrombosis: implications of published guidelines for clinical practice. Ann Oncol 2009; 20: 1619-1630.