Diagnostik und Therapie Tumorassoziierter venöser Thromboembolien – was sagen die Leitlinien?

Zusammenfassung

Tumorwachstum und Gerinnungsaktivierung sind pathophysiologisch eng miteinander verknüpft. Deshalb sind Tumor-assoziierte venöse Thromboembolien (VTE) häufig. Während stationär aufgenommene Tumorpatienten eine Thromboseprophylaxe erhalten wird dies für ambulante Patienten in der Regel nicht empfohlen. Wenn Tumorpatienten doch eine VTE entwickeln, dann sollten sie mit einem NMH in therapeutischer Dosis für 3–6 Monate behandelt werden. Vitamin-KAntagonisten haben ein höheres Blutungsrisiko und für NOAKs gibt es noch keine ausreichenden Daten. Nicht nur Hämato-Onkologen, sondern alle Ärzte, die Tumorpatienten betreuen, sollten mit den aktuellen Leitlinienempfehlungen vertraut sein. Auch die Patienten sollten über die Symptome einer VTE informiert sein.

Summary

Oncogenic transformation is closely linked to coagulation activation and cancer-associated venous thromboembolism (VTE) is a common problem. Guidelines recommend thromboprophylaxis with a low molecular weight heparin for hospitalized cancer patients. However, thromboprophylaxis is not customarily advised for ambulatory cancer patients. Cancer patients with VTE are usually treated with a low molecular weight heparin for 3–6 months. Vitamin K antagonists have a higher bleeding risk and there are not sufficient data to recommend any of the new oral anticoagulants. All physicians taking care of cancer patients should be aware of the current guideline recommendations. Oncology professionals should educate patients about the signs of VTE.

English version available at: http://www.phlebologieonline.de

Schlüsselwörter

Krebs - venöse Thromboembolie - Leitlinien - Tumor - Prophylaxe

Keywords

Cancer - venous thromboembolism - guidelines - tumour - prophylaxis

• Literatur

• 1 Farge D, Debourdeau P, Beckers M. et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost 2013; 11: 56-70.
• 2 NCCN Clinical Practice Guidelines in Oncology. Cancer-associated venous thromboembolic disease. Version 1/2014, www.nccn.org (abgefragt 9/2015)
• 3 Lyman GH, Khorana AA, Kuderer NM. et al. American Society of Clinical Oncology Clinical Practice Guideline. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013; 31: 2189-2204.
• 4 Lyman GH, Bohlke K, Khorana AA. et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update 2014. J Clin Oncol 2015; 33: 654-656.
• 5 Robert Koch-Institut. (Hrsg.) Verbreitung von Krebserkrankungen in Deutschland. Entwicklung der Prävalenzen zwischen 1990 und 2010. Beiträge zur Gesundheitsberichterstattung des Bundes. RKI; Berlin: 2010
• 6 Falanga A, Zacharski L. Deep vein thrombosis in cancer: the scale of the problem and approaches to management. Ann Oncol 2005; 16: 696-701.
• 7 Khorana AA, Kuderer NM, Culakova E. et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111: 4902-4907.
• 8 Carrier M, Khorana AA, Moretto P. et al. Lack of evidence to support thromboprophylaxis in hospitalized medical patients with cancer. Am J Med 2014; 127: 82-86.
• 9 Langer F, Bokemeyer C. Crosstalk between cancer and haemostasis. Implications for cancer biology and cancer-associated thrombosis with focus on tissue factor. Hämostaseologie 2012; 32: 95-104.
• 10 Langer F. Hämostaseologische Aspekte in der Onkologie. Hämostaseologie 2015; 35: 152-164.
• 11 Gil-Bernabé A, Lucotti S, Muschel RJ. Coagulation and metastasis: what does the experimental literature tell us?. Br J Haematol 2013; 162: 433-441.
• 12 Hisada Y, Geddings JE, Ay C, Mackman N. Venous thrombosis and cancer: from mouse models to clinical trials. J Thromb Haemost 2015; 13: 1372-1382.
• 13 Lechner D, Weltermann A. Pathophysiologie der Chemotherapie-assoziierten Thrombose. Hämostaseologie 2008; 28: 112-120.
• 14 Haddad TC, Greeno EW. Chemotherapy-induced thrombosis. Thromb Res 2006; 118: 555-568.
• 15 Di Nisio M, Lee AYY, Carrier M. Subcommittee on Haemostasis and Malignancy. for the et al. Diagnosis and treatment of incidental venous thromboembolism in cancer patients: guidance from the SSC of the ISTH. J Thromb Haemost 2015; 13: 880-883.
• 16 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.
• 17 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. J Thromb Haemost 2006; 04: 2384-2390.
• 18 Agnelli G, Gussoni G, Bianchini C. PROTECHT Investigators. 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.
• 19 Agnelli G, George DJ, Kakkar AK. SAVEONCO Investigators. et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012; 366: 601-609.
• 20 Cesarone MR, Ledda A, Nicolaides A. et al. Threemonth, outpatient, oral anticoagulant treatment in comparison with low-molecular-weight heparin in cancer patients. Supplement to Circulation 2003; 108 abstr. 2875.
• 21 Lee AY, Levine MN, Baker RI. CLOT Investigators. et al. 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.
• 22 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.
• 23 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: 389-96.
• 24 Hull RD, Pineo GF, Brant RF. LITE Trial Investigators. et al. Long-term Low-Molecular-Weight Heparin versus Usual Care in Proximal-Vein Thrombosis Patients with Cancer. Am J Med 2006; 119: 1062-1072.
• 25 Lee AY, Kamphuisen PW, Meyer G. CATCH Investigators. et al. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. JAMA 2015; 314: 677-686.
• 26 Ridker PM, Goldhaber SZ, Danielson E. et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348: 1425-1434.
• 27 Kearon C, Ginsberg JS, Kovacs MJ. et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349: 631-639.
• 28 Francis CW, Kessler CM, Goldhaber SZ. et al. Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN Study. J Thromb Haemost 2015; 13: 1028-1035.
• 29 Carrier M, Le Gal G, Cho R. et al. Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients. J Thromb Haemost 2009; 07: 760-765.
• 30 Ihaddadene R, Le Gal G, Delluc A, Carrier M. Dose escalation of low molecular weight heparin in patients with recurrent cancer-associated thrombosis. Thromb Res 2014; 134: 93-95.
• 31 Schiff D, Lee EQ, Nayak L, Norden AD. et al. Medical management of brain tumors and the sequelae of treatment. Neuro Oncol 2015; 17: 488-504.
• 32 Donato J, Campigotto F, Uhlmann EJ. et al. Intracranial hemorrhage in patients with brain metastases treated with therapeutic enoxaparin: a matched cohort study. Blood 2015; 126: 494-499.
• 33 Launay-Vacher V, Oudard S, Janus N. et al. Renal Insufficiency and Cancer Medications (IRMA) Study Group. Prevalence of Renal Insufficiency in cancer patients and implications for anticancer drug management: the renal insufficiency and anticancer medications (IRMA) study. Cancer 2007; 110: 1376-1384.
• 34 Harder S. Anticoagulant dosing in renal impairment. Phlebologie 2015; 44: 316-319.
• 35 Short NJ, Connors JM. New oral anticoagulants and the cancer patient. Oncologist 2014; 19: 82-93.