Рак-ассоциированный тромбоз при проведении химиотерапии: лечение и профилактика

Королева И.А., Копп М.В. Рак-ассоциированный тромбоз при проведении химиотерапии: лечение и профилактика. Consilium Medicum. 2022;24(6):422–428. DOI: 10.26442/20751753.2022.6.201724

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Koroleva IA, Kopp MV. Cancer-associated thrombosis during chemotherapy: treatment and prevention: A review. Consilium Medicum. 2022;24(6):422–428. DOI: 10.26442/20751753.2022.6.201724

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Аннотация

Рак-ассоциированный тромбоз является сегодня значимой проблемой как для онкологов, так и сосудистых хирургов. У пациентов со злокачественными новообразованиями частота возникновения симптомных венозных тромбоэмболических осложнений (ВТЭО) в 4–7 раз выше, чем в общей популяции. Наличие отдаленных метастазов при солидных опухолях повышает риск венозных тромбозов. Наиболее часто ВТЭО развиваются при раке поджелудочной железы и раке желудка. Химиотерапия увеличивает риск развития ВТЭО. Для лечения ВТЭО у больных при проведении химиотерапии используют низкомолекулярные гепарины и прямые оральные антикоагулянты. Результаты исследования СARAVAGGIO продемонстрировали, что апиксабан не уступает дальтепарину в лечении ВТЭО у больных активным раком и не увеличивает риск кровотечений. Перед началом химиотерапии необходимо оценить риск развития ВТЭО, используя шкалу Khorana. Амбулаторным пациентам с раком высокого риска (оценка по шкале Khorana >2 до начала нового режима системной химиотерапии) может быть назначена тромбопрофилактика низкомолекулярным гепарином. Представляется перспективной идея использования прямых оральных антикоагулянтов, но пока это за рамками одобренных показаний.

Ключевые слова: рак-ассоциированный тромбоз, венозные тромбоэмболические осложнения, прямые оральные антикоагулянты, апиксабан

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Cancer-associated thrombosis is a significant problem today for both oncologists and vascular surgeons. In patients with malignant neoplasms the incidence of symptomatic venous thromboembolism (VTE) is 4–7 times higher than in the general population. The presence of distant metastases in solid tumors increases the risk of VTE. Most often, VTE develop in pancreatic cancer and stomach cancer. Chemotherapy increases the risk of developing VTE. Low-molecular-weight heparin and direct oral anticoagulants are used for the treatment of VTE in patients with chemotherapy. The results of the СARAVAGGIO study demonstrated that apixaban is not inferior to dalteparin in the treatment of VTE in patients with active cancer and does not increase the risk of bleeding. Before starting chemotherapy, it is necessary to assess the risk of developing VTE using the Khorana risk score. Outpatient patients with high-risk cancer (Khorana score >2 before the start of a new systemic chemotherapy regimen) may be prescribed thromboprophylaxis with low molecular weight heparin. The idea of using direct oral anticoagulants seems promising, but so far it is beyond the scope of approved indications.

Keywords: cancer-associated thrombosis, venous thromboembolism, direct oral anticoagulants, apixaban

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Список литературы

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1. Khorana AA, Dalal M, Lin J, Connolly G.C. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer. 2013;119:648-55. DOI:10.1002/cncr.27772
2. Nobel S, Pasi J. Epidemiology and pathophysiology of cancer-associated thrombosis. Br J Cancer. 2010;102(Suppl. 1):S2-9. DOI:10.1038/sj.bjc.6605599
3. Kessler CM. The link between cancer and venous thromboembolism: a review. Am J Clin Oncol. 2009;32(4 Suppl.):S3-7. DOI:10.1097/COC.0b013e3181b01b17
4. Trousseau A. Phlegmasia alba dolens. Clinique medicale de 1’Hotel-Dieu de Paris. 2nd ed. Paris: Ballière, 1865.
5. Blann AD, Dunmore S. Arterial and Venous Thrombosis in Cancer Patients. Cardiol Res Pract. 2011;2011:394740. DOI:10.4061/2011/394740
6. Lip GY, Chin BS, Blann AD. Cancer and the prothrombotic state. Lancet Oncol. 2002;3(1):27-34. DOI:10.1016/s1470-2045(01)00619-2
7. Staszewski H. Hematological paraneoplastic syndromes. Semin Oncol. 1997;24(3):329-33.
8. Blom JW, Doggen CJM, Osanto S, Rosendaal FR. Malignancies, Prothrombotic Mutations, and the Risk of Venous Thrombosis. JAMA. 2005;293(6):715-22. DOI:10.1001/jama.293.6.715
9. Walker AJ, Card TR, West J, et al. Incidence of venous thromboembolism in patients with cancer – a cohort study using linked United Kingdom databases. Eur J Cancer. 2013;49(6):1404-13. DOI:10.1016/j.ejca.2012.10.021
10. Barsam SJ, Patel R, Arya R. Anticoagulation for prevention and treatment of cancer-related venous thromboembolism. Br J of Haematol. 2013;161(6):764-77. DOI:10.1111/bjh.12314
11. Lecumberri R, Marqués M, Panizo E, et al. High incidence of venous thromboembolism despite electronic alerts for thromboprophylaxis in hospitalised cancer patients. Thromb Haemost. 2013;110(1):184-90. DOI:10.1160/TH13‑02‑0131
12. Königsbrügge O, Pabinger I, Ay C. Risk factors for venous thromboembolism in cancer: novel findings from the Vienna Cancer and Thrombosis Study (CATS). Thromb Res. 2014;133:S39-43. DOI:10.1016/S0049–3848(14)50007–2
13. Chew HK, Wun T, Harvey D, et al. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med. 2006;166(4):458-64. DOI:10.1001/archinte.166.4.458
14. Falanga A, Marchetti M, Russo L. Venous thromboembolism in the hematologic malignancies. Curr Opin Oncol. 2012;24(6):702-10. DOI:10.1097/CCO.0b013e3283592331
15. Farge D, Bosquet L, Kassab-Chahmi D, et al. SOR. 2008 French national guidelines for the treatment of venous thromboembolism in patients with cancer: report from the working group. Crit Rev Oncol Hematol. 2010;73(1):31-46. DOI:10.1016/j.critrevonc.2008.12.004
16. Singh RT, Sousou T, Mohile S, Khorana AA. High rates of symptomatic and incidental thromboembolic events in gastrointestinal cancer patients. J Thromb Haemost. 2010;8(8):1879-81. DOI:10.1111/j.1538-7836.2010.03929.x
17. Blom JW, Vanderschoot JP, Oostindier MJ, et al. Incidence of venous thrombosis in a large cohort of 66329 cancer patients: record of a linkage study. J Thromb Haemost. 2006;4(3):529-35. DOI:10.1111/j.1538-7836.2006.01804.x
18. Khorana AA, Francis CW, Culakova E, et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5(3):632-4. DOI:10.1111/j.1538-7836.2007.02374.x
19. Donnellan E, Kevane B, Bird BR, Ainle FN. Cancer and venous thromboembolic disease: from molecular mechanisms to clinical management. Curr Oncol. 2014;21(3):134-43. DOI:10.3747/co.21.1864
20. Khorana AA, Francis CW, Culakova E, et al. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer. 2007;110:2339-46. DOI:10.1002/cncr.23062
21. Mandalà M, Falanga A, Roila F. Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2011;22(Suppl. 6):vi85-92. DOI:10.1093/annonc/mdr392
22. Stein PD, Kayali F, Silbergleit A, et al. Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med. 2006;119(1):60-8. DOI:10.1016/j.amjmed.2005.06.058
23. Stein PD, Beemath A, Meyers FA, et al. Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med. 2006;119(1):60-8. DOI:10.1016/j.amjmed.2005.06.058
24. Khorana AA, Francis CW, Culakova E, et al. Thromboembolism in hospitalized neutropenic cancer patients. J Clin Oncol. 2006;24(3):484-90. DOI:10.1200/JCO.2005.03.8877
25. Lyman GH, Eckert L, Wang Y, et al. Venous thromboembolism risk in patients with cancer receiving chemotherapy: a real-world analysis. Oncologist. 2013;18(12):1321-9. DOI:10.1634/theoncologist.2013-0226
26. 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):2277-85. DOI:10.1001/jama.2008.656
27. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 2005;97:1652-62. DOI:10.1016/S1470-2045(14)71171-4
28. Vogel VG, Costantino JP, Wickerham DL, et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 trial: preventing breast cancer. Cancer Prev Res (Phila). 2010;3:696-706. DOI:10.1158/1940-6207.CAPR-10-0076
29. 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):914-24. DOI:10.1001/jama.299.8.914
30. Khorana AA, Francis CW, Culakova E, et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost. 2007;5(3):632-4. DOI:10.1111/j.1538-7836.2007.02374.x
31. Horsted F, West J, Grainge M. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLOS Med. 2012;9(7):e1001275. DOI:10.1371/journal.pmed.1001275
32. Streiff MB, Bockenstedt PL, Cataland SR, et al. Venous thromboembolic disease. J Natl Compr Canc Netw. 2011;9(7):714-77. DOI:10.6004/jnccn.2011.0062
33. Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet. 1960;1:1309-12.
34. Hirsh J, Bates SM. Clinical trials that have influenced the treatment of venous thromboembolism: a historical perspective. Ann Intern Med. 2001;134(5):409-17.
DOI:10.7326/0003-4819-134-5-200103060-00013
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36. Monreal M, Falgá C, Valdés M, et al; Riete Investigators. Fatal pulmonary embolism and fatal bleeding in cancer patients with venous thromboembolism: findings from the RIETE registry. J Thromb Haemost. 2006;4(9):1950-6. DOI:10.1111/j.1538-7836.2006.02082.x
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Авторы

И.А. Королева*, М.В. Копп

ЧУ ООВО «Медицинский университет “Реавиз”», Самара, Россия
*кorolevaia_sаmara@mail.ru

________________________________________________

Irina A. Koroleva*, Mikhail V. Kopp

Medical University “Reaviz”, Samara, Russia
*кorolevaia_sаmara@mail.ru

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