Subscribe to RSS
DOI: 10.1055/s-0037-1618984
Heparine – DOAKs – VKA
Pro und Contra unter besonderer Berücksichtigung von TumorpatientenHeparins – DOACS – VKAPros and Cons in consideration of tumour patientsPublication History
Publication Date:
10 January 2018 (online)
Zusammenfassung
Bei Tumorpatienten bestehen ein erhöhtes Thromboembolierisiko und nicht selten gleichzeitig ein erhöhtes Blutungsrisiko. Dies macht die Antikoagulation nicht ganz einfach. Es muss stets eine individuelle Nutzen-Risiko-Abwägung erfolgen. Stationäre Tumorpatienten erhalten in der Regel eine medikamentöse VTE-Prophylaxe meist mit einem niedermolekularen Heparin (NMH) in der Hochrisikoprophylaxedosierung. Bei ambulanten Tumorpatienten ist das VTE-Risiko deutlich geringer, sie erhalten nur dann eine medikamentöse Prophylaxe, wenn zusätzliche prothrombogene Risikofaktoren vorliegen. Tumorpatienten mit akuter VTE werden mindesten 3–6 Monate mit NMH in therapeutischer (gewichtsadaptierter) Dosis behandelt, erst danach kann man ggf. auf Vitamin-K-Antagonisten umsetzen. Neben den etablierten Antikoagulanzien wie Heparinen, Vitamin-K-Antagonisten, Fondaparinux sind in den letzten Jahren die direkten oralen Antikoagulantien (DOAKs) hinzugekommen. Die Zulassung der DOAKs erstreckt sich aktuell auf die Thromboembolieprophylaxe nach elektiver Hüft- und Knietotalendoprothese, der Schlaganfallprophylaxe bei nicht-valvulärem Vorhofflimmern und der Initial- und Folgetherapie nach tiefer Beinvenenthrombose und Lungenembolie. In den Phase-III-Studien waren ca. 4–10 % Tumorpatienten integriert. Die DOAKs haben hierbei gezeigt, dass sie mindestens gleichwertig sind im Vergleich zur Standardtherapie bezüglich Rezidiv-VTE bei vergleichbarer Blutungsrate. Dies ist ermutigend. Die Datenlage reicht aktuell jedoch noch nicht aus, um sie bei Tumorpatienten einzusetzen. Entsprechende Studien speziell für Tumorpatienten stehen noch aus.
Summary
Patients with cancer are at increased risk of venous thromboembolism (VTE). At the same time they have often an underlying bleeding risk. That can often make decisions surrounding the administration of anticoagulants complicate. Individual risk-benefit calculation is necessary. During hospital stage the patients get, if there are no contraindications, a medical VTE prophylaxis with low molecular weight heparin (LMWH). Whereas outpatients don`t get a prophylaxis because they are at low risk of thromboembolism. If additional risk factor for VTE exists a decision for medical VTE prophylaxis should be taken into account. In patients with cancer and acute VTE, LMWH is recommended as treatment of choice for initial and long-term management in a body weight adapted dosage. After a period of 3–6 months and if a prolonged treatment is necessary, guidelines allow to switch from LMWH to VKA for further anticoagulant therapy. Beside the established anticoagulants like heparin, vitamin K antagonists, fondaparinux new oral direct anticoagulants (DOACs) were established in the last years. These substances are evaluated in in clinical trials. They are approved for treatment of acute VTE, for secondary prophylaxis and for prevention of ischemic stroke in patients with arterial fibrillation. In the VTE trials, 4–10 % of the enrolled patients had a history of cancer. The data shows that DOACs can prevent recurrent VTE as good as standard therapy with enoxaparin/warfarin without more bleeding complications. The results are encouraging. Because of the limited data the direct oral anticoagulants are not recommended for treatment of VTE at this time. Further studies are necessary.
English version available at www.phlebologieonline.de
-
Literatur
- 1 Schinzel H. Antithrombotika und Fibrinolyse - therapie. In: Wolff H-P, Weihrauch TR. Internistische Therapie: 2014/2015. Berlin: Elsevier, 20. Aufl. 2014: 301-341.
- 2 Eikelboom JW, Weitz JI. Update on Antithrombotic Therapy. New Anticoagulants. Circulation 2010; 121: 1523-1532.
- 3 Eriksson BI, Quinlan DJ, Eikelboom JW. Novel oral factor Xa and thrombin inhibitors in the management of thromboembolism. Annu Rev Med 2011; 62: 41-57.
- 4 Pollack CV, Reilly PA, Eikelboom J. et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015; 373: 511-520.
- 5 Alikhan R. The new oral anticoagulants and management of bleeding. Br J Cardiol 2014; 21: 69-71.
- 6 Ebright J, Mousa SA. Oral anticoagulants and status of antidotes for the reversal of bleeding risk. Clin Appl Thromb Hemost 2015; 21 (02) 105-114.
- 7 Levitan N, Dowlati A, Remick SC. et al. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine (Baltimore) 1999; 78: 285-29.
- 8 Heit JA, Silverstein MD, Mohr DN. et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; Mar 27; 160 (06) 809-815.
- 9 Sallah S, Wan JY, Nguyen NP. Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost 2002; 87: 575-579.
- 10 Blom JW, Doggen CJ, Osanto S. et al. Prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293: 715-722.
- 11 Khorana AA, Francis CW, Culakova E, Lyman GH. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 2005; 104: 2822-2829.
- 12 Blom JW, Vanderschoot JP. Oostindiër 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; 04: 529-535.
- 13 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.
- 14 Khorana AA, Connolly GC. Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol 2009; 27: 4839-4847.
- 15 Falanga A. The incidence and risk of venous thromboembolism associated with cancer and nonsurgical cancer treatment. Cancer Invest 2009; 27: 105-115.
- 16 Pabinger I, Ay C. Risk of venous thromboembolism and primary prophylaxis in cancer. Hämostaseologie 2011; 04: 1-6.
- 17 Prandoni P, Lensing AW, 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.
- 18 Kahn SR, Lim W, Dunn AS. et al. Prevention of VTE in nonsurgical patients: antithrombotic ther- apy and prevention of thrombosis, 9th ed: Am College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141: e195S-e226S.
- 19 Gould MK, Garcia DA, Wren SM. et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141: e195S-e226S.
- 20 Agnelli G, Verso M. Management of venous thromboembolism in patients with cancer. J Thromb Haemost 2011; 09 (Suppl. 01) 316-324.
- 21 Khorana AA, Kuderer NM, Culakova E. et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111: 4902-4907.
- 22 Encke A. et al. S3-Leitlinien zur venösen Thrombeoembolie (VTE). 2. komplett überarbeitete Auflage. Stand 15.10.2015. htttp://.awmf.org/leitlinien
- 23 Geerts WH, Bergqvist D. Pineo et al. Prevention of venous thromboembolism: antithrombotic therapy and prevention of thrombosis, 8th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2008: e381S-e453S.
- 24 Lee A, Levine MN, Ross I. 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.
- 25 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.
- 26 Lee A, Bauersachs R, Janas MS. et al. CATCH: a randomised clinical trial comparing long-term tinzaparin versus warfarin for treatment of acute venous thromboembolism in cancer patients. BMC Cancer 2013; 13: 284-297.
- 27 Gerotziafas GT, Mahe I, Elalamy I. New orally active anticoagulant agents for the prevention and treatment of venous thromboembolism in cancer patients. Ther Clin Risk Manag 2014; 10: 423-436.
- 28 Kearon C, Akl EA, Comerota AJ. et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis. Am College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141 (Suppl. 02) e419S-e494S.
- 29 Lyman GH. Venous thromboembolism in the patient with cancer. Cancer 2011; 117 (07) 1334-1349.