Артериальная тромбоэмболия (ишемический инсульт, острая окклюзия периферических артерий) у больных со злокачественными заболеваниями: диагностика, профилактика, лечение. Обзор литературы. Часть 2

Злокачественные новообразования (ЗНО) и противоопухолевая терапия увеличивают риск развития артериальной тромбоэмболии (АТЭ) (ишемического инсульта, острой артериальной окклюзии периферических артерий). В статье представлены частота развития АТЭ у данных пациентов, факторы риска развития АТЭ в зависимости от видов ЗНО, а также особенности профилактики и лечения АТЭ-осложнений у больных с ЗНО.

1. Costamagna G., Hottinger A., Milionis H., Lambrou D., Salerno A., Strambo D., Livio F., Navi B.B., Michel P. Clinical and demographic characteristics, mechanisms, and outcomes in patients with acute ischemic stroke and newly diagnosed or known activecancer. Neurology, 2023; 100 (24): e2477‒e2489. doi: 10.1212/WNL.0000000000207341

2. Navi B.B., Reiner A.S., Kamel H., Iadecola C., Okin P.M., Elkind M.S.V., Panageas K.S., DeAngelis L.M. Risk of arterial thromboembolism in patients with cancer. J. Am. Coll. Cardiol., 2017; 70 (8): 926‒938. doi: 10.1016/j.jacc.2017.06.047

3. Mulder F.I., Horváth-Puhó E., van Es N., Pedersen L., Büller H.R., Bøtker H.E., Sørensen H.T. Arterial thromboembolism in cancer patients: a danish population-based cohort study. JACC CardioOncol., 2021; 3 (2): 205‒218. doi: 10.1016/j.jaccao.2021.02.007

4. Navi B.B., Reiner A.S., Kamel H., Iadecola C., Elkind M.S, Panageas K.S., DeAngelis L.M. Association between incident cancer and subsequent stroke. Ann. Neurol., 2015; 77 (2): 291‒300. doi: 10.1002/ana.24325

5. Chen P.C., Muo C.H., Lee Y.T., Yu Y.H., Sung F.C. Lung cancer and incidence of stroke: a population-based cohort study. Stroke, 2011; 42 (11): 3034‒309. doi: 10.1161/STROKEAHA.111.615534

6. Kuan A.S., Teng C.J., Wu H.H., Su V.Y., Chen Y.T., Chien S.H.., Yeh CM., Hu L.Y., Chen T.J., Tzeng C.H., Liu C.J. Risk of ischemic stroke in patients with ovarian cancer: a nationwide population-based study. BMC Med., 2014; 12: 53. doi: 10.1186/1741-7015-12-53

7. Navi B.B., Singer S., Merkler A.E., Cheng N.T., Stone J.B., Kamel H., Iadecola C., Elkind M.S., DeAngelis L.M. Recurrent thromboembolic events after ischemic stroke in patients with cancer. Neurology, 2014; 83 (1): 26‒33. doi: 10.1212/WNL.0000000000000539

8. Sonbol Y.T., Elgenidy A., Awad A.K., Elmehrath A.O., Kobeissi H., Afifi A.M., Ghozy S. Stroke as a cause of death in patients with cancer: a SEER-based study. J. Stroke Cerebrovasc. Dis., 2023; 32 (8): 107154. doi: 10.1016/j.jstrokecerebrovasdis.2023.107154

9. Dittrich T.D., Aujesky M., Rudin S., Zietz A., Wagner B., Polymeris A., Altersberger V.L., Sinnecker T., Gensicke H., Engelter S.T., Lyrer P., Hess V., Sutter R., Nickel C.H., Bonati L.H., Fischer U., Psychogios M., Katan M., De Marchis G.M. Apical pulmonary lesions suspected of malignancy visible on neck CT angiography performed for acute stroke: Prevalence, treatment, and clinical implications ‒ the PLEURA study. Eur. Stroke J., 2023; 8 (2): 549‒556. doi: 10.1177/23969873231151488

10. Ha J., Lee M.J.., Kim S.J., Park B.Y., Park H., Cho S., Chung J.W., Seo W.K., Kim G.M., Bang O.Y., Chung C.S. Prevalence and impact of venous and arterial thromboembolism in patients with embolic stroke of undetermined source with or without active cancer. J. Am. Heart. Assoc., 2019; 8 (21): e013215. doi: 10.1161/JAHA.119.013215

11. Brenner B., Bikdeli B., Tzoran I., Madridano O., Lуpez-Reyes R., Suriñach J.M., Blanco-Molina Á., Tufano A., Núñez J.J.L., Trujillo-Santos J., Monreal M. RIETE Investigators. Arterial ischemic events are a major complication in cancer patients with venous thromboembolism. Am. J. Med., 2018; 131 (9): 1095‒1103. doi: 10.1016/j.amjmed.2018.04.037

12. Sun M.Y., Bhaskar S.M.M. bridging the gap in cancer-related stroke management: update on therapeutic and preventive approaches. Int. J. Mol. Sci., 2023; 24 (9): 7981. doi: 10.3390/ijms24097981

13. Fitzpatrick T., Carrier M., Le Gal G. Cancer, atrial fibrillation, and stroke. Thromb. Res., 2017; 155: 101‒105. doi: 10.1016/j.thromres.2017.05.006

14. Lun R., Roy D.C., Hao Y., Deka R., Huang W.K., Navi B.B., Siegal D.M., Ramsay T., Fergusson D., Shorr R., Dowlatshahi D. Incidence of stroke in the first year after diagnosis of cancer-A systematic review and meta-analysis. Front. Neurol., 2022; 13: 966190. doi: 10.3389/fneur.2022.966190

15. Navi B.B., Kasner S.E., Elkind M.S.V., Cushman M., Bang O.Y., DeAngelis L.M. Cancer and embolic stroke of undetermined source. Stroke, 2021; 52 (3): 1121‒1130. doi: 10.1161/STROKEAHA.120.032002

16. Bamias A., Tzannis K., Zakopoulou R., Sakellakis M., Dimitriadis J., Papatheodoridi A., Rallidis L., Halvatsiotis P., Tsiara A., Kaparelou M., Kostouros E., Barbarousi D., Koutsoukos K., Fragiadis E., Dellis A.E., Anastasiou I., Stravodimos K., Pinitas A., Papatsoris A., Adamakis I., Varkarakis I., Fragoulis C., Pagoni S., Matsouka C., Skolarikos A., Mitropoulos D., Doumas K., Deliveliotis C., Constantinides C., Dimopoulos M.A. Risk for arterial thromboembolic events (ATEs) in patients with advanced urinary tract cancer (aUTC) treated with firstline chemotherapy: single-center, observational study. Curr. Oncol., 2022; 29 (9): 6077‒6090. doi: 10.3390/curroncol29090478

17. Виценя М.В., Агеев Ф.Т., Гиляров М.Ю., Овчинников А.Г., Орлова Р.В., Полтавская М.Г., Сычева Е.А. Практические рекомендации по коррекции кардиоваскулярной токсичности противоопухолевой лекарственной терапии. Злокачественные опухоли, 2019: 9 (3S2): 609–627. doi: 10.18027/22245057-2019-9-3s2-609-627 [Vitsenya M.V., Ageev F.T., Gilyarov M.Yu., Ovchinnikov A.G., Orlova R.V., Poltavskaya M.G., Sycheva E.A. Practical recommendations for the correction of cardiovascular toxicity of antitumor drug therapy. Malignant tumors, 2019: 9 (3S2): 609–627. (In Russ.)]. doi: 10.18027/22245057-2019-9-3s2-609-627

18. Yhim H.Y., Lee J., Kim K.H., Kim S.A., Lee J.Y., Hwang H.G., Hong J., Lee J.O., Bang S.M. Increased risk of venous and arterial thromboembolism in patients with colorectal cancer receiving cetuximabbased combination chemotherapy: A population-based study in Korea. Thromb. Res., 2023; 231: 50‒57. doi: 10.1016/j.thromres.2023.10.005

19. Kelly A., Toale C., Moloney M.A., Kavanagh E.G. Outcomes of acute limb ischaemia in patients with underlying malignancy: a systematic review. EJVES Vasc. Forum, 2021; 54: 13‒20. doi: 10.1016/j.ejvsvf.2021.10.019

20. Sundbøll J., Veres K., Horváth-Puhó E., Adelborg K., Sørensen H.T. Risk and prognosis of cancer after lower limb arterial thrombosis. Circulation, 2018; 138 (7): 669‒677. doi: 10.1161/CIRCULATIONAHA.117.032617

21. Valent P., Hadzijusufovic E., Schernthaner G.H., Wolf D., Rea D., le Coutre P. Vascular safety issues in CML patients treated with BCR/ABL1 kinase inhibitors. Blood, 2015; 125 (6): 901‒906. doi: 10.1182/blood-2014-09-594432

22. El Sakka K., Gambhir R.P.S., Halawa M., Chong P., Rashid H. Association of malignant disease with critical leg ischaemia. Br. J .Surg., 2005; 92: 1498–1501. doi:10.1002/bjs.5125

23. Tsang J.S., Naughton P.A., O’Donnell J., Wang T.T., Moneley D.S., Kelly C.J., Leahy A.L. Acute limb ischemia in cancer patients: should we surgically intervene? Ann. Vasc. Surg., 2011; 25 (7): 954‒960. doi: 10.1016/j.avsg.2011.06.002

24. Larsen T.L., Brekke J., Garresori H., Frøen H., Jacobsen E.M., Torfoss D., Wik H.S., Enden T.R., Porojnicu A.C., Quist-Paulsen P., Velle E., Sandset P.M., Ree A.H., Dahm A.E.A. Arterial thromboembolism in cancer patients treated with apixaban. Blood, 2022; 140 (Supp. 1): 11366–11367. doi: 10.1182/ blood-2022-160363

25. Lesterhuis W.J., van Spronsen D.J., Schultze-Kool L.J., de Mulder P.H. Acute arterial occlusion after chemotherapy for testicular cancer. Lancet Oncol., 2005; 6 (11): 910. doi: 10.1016/S1470-2045(05)70428-9

26. Grilz E., Königsbrügge O., Posch F., Schmidinger M., Pirker R., Lang I.M., Pabinger I., Ay C. Frequency, risk factors, and impact on mortality of arterial thromboembolism in patients with cancer. Haematologica, 2018; 103 (9): 1549‒1556. doi: 10.3324/haematol.2018.192419

27. Lapébie F.X., Aboyans V., Lacroix P., Constans J., Boulon C., Messas E., Ferrières J., Bongard V., Bura-Rivière A. Editor’s choice ‒ External applicability of the COMPASS and VOYAGER-PAD trials on patients with symptomatic lower extremity artery disease in France: The COPART registry. Eur. J. Vasc. Endovasc. Surg., 2021; 62 (3): 439‒449. doi: 10.1016/j.ejvs.2021.05.028

28. Nicolajsen C.W., Dickenson M.H., Budtz-Lilly J., Eldrup N. Frequency of cancer in patients operated on for acute peripheral arterial thrombosis and the impact on prognosis. J. Vasc. Surg., 2015; 62 (6): 1598‒1606. doi: 10.1016/j.jvs.2015.06.223

29. Govsyeyev N., Malgor R.D., Hoffman C., Harroun N., Sturman E., Al-Musawi M., Malgor E.A., Jacobs D.L., Nehler M. A systematic review and meta-analysis of outcomes after acute limb ischemia in patients with cancer. J. Vasc. Surg., 2021; 74 (3): 1033‒1040.e1. doi: 10.1016/j.jvs.2021.03.058

30. Javid M., Magee T.R., Galland R.B. Arterial thrombosis associated with malignant disease. Eur. J. Vasc. Endovasc. Surg., 2008; 35 (1): 84‒87. doi: 10.1016/j.ejvs.2007.08.014

31. Morris-Stiff G., Lewis M.H. Surgical treatment of acute limb ischaemia in the presence of malignancy. Int. J. Surg., 2010; 8 (3): 233‒235. doi: 10.1016/j.ijsu.2010.01.007

32. Pernod G., Cohen A., Mismetti P., Sanchez O., Mahé I. INNOVTE CAT Working Group. Cancerrelated arterial thromboembolic events. Arch. Cardiovasc. Dis., 2024; 117 (1): 101‒113. doi: 10.1016/j.acvd.2023.11.007

33. Liu Y., Wang J., Guo L., Ping L. Risk factors of embolism for the cardiac myxoma patients: a systematic review and metanalysis. BMC Cardiovasc. Disord., 2020; 20 (1): 348. doi: 10.1186/s12872-02001631-w

34. Chandler C. Malignant arterial tumor embolization. J. Surg. Oncol., 1993; 52 (3): 197‒202. doi: 10.1002/jso.2930520317

35. Hussain S.M.A. Tumor embolism and acute arterial occlusion: A systematic review. Surgery Open Science, 2022; 10: 216–222. doi.org/10.1016/j. sopen.2022.10.006

36. Qin Y., Zhang L., Liang X., Sun X., Wang N., Yuan M., Wang Q., Wu D. Venous and arterial thromboembolism in patients with metastatic lung cancer. Clin. Appl. Thromb. Hemost., 2023; 29: 10760296231159121. doi: 10.1177/10760296231159121

37. Mitrovic M., Pantic N., Sabljic N., Bukumiric Z., Virijevic M., Pravdic Z., Cvetkovic M., Rajic J., Bodrozic J., Milosevic V., Todorovic-Balint M., Vidovic A., Suvajdzic-Vukovic N., Antic D. Arterial thrombosis in patients with acute myeloid leukemia: incidence and risk factors. Cancers (Basel), 2023; 15 (11): 3060. doi: 10.3390/cancers15113060

38. Akabane K., Watanabe T., Tajima Y., Toyama S., Tamate Y., Uchida T. Case Report: Acute arterial occlusion of the right lower extremity due to left atrial invasion from pulmonary metastases of thyroid cancer. Front. Cardiovasc. Med., 2023; 10: 1221180. doi: 10.3389/fcvm.2023.1221180

39. Abraham K.P., Reddy V., Gattuso P. Neoplasms metastatic to the heart: review of 3314 consecutive autopsies. Am. J. Cardiovasc. Pathol., 1990; 3 (3): 195‒198.

40. Klatt E.C., Heitz D.R. Cardiac metastases. Cancer, 1990; 65 (6): 1456‒1459. doi: 10.1002/1097-0142(19900315)65:6<1456::aidcncr2820650634>3.0.co;2-5

41. Kaschwich M., Peters F., Hischke S., Rieß H.C., Gansel M., Marschall U., L’Hoest H., Heidemann F., Debus E.S., Acar L., Kreutzburg T., Behrendt C.A. Long-term incidence of cancer after index treatment for symptomatic peripheral arterial disease ‒ a health insurance claims data analysis. Vasa, 2020; 49 (6): 493‒499. doi: 10.1024/0301-1526/a000901

42. Navi B.B., Reiner A.S., Kamel H., Iadecola C., Elkind M.S., Panageas K.S., DeAngelis L.M. OC-02 ‒ Risk of arterial thromboembolism in patients with breast cancer. Thromb. Res., 2016; 140 Suppl 1: S169. doi: 10.1016/S0049-3848(16)30119-0

43. González Rodríguez P., Gisbert S.M.M., Chiriboga Granja J.I., Medina M.C., Palonés F.J.G. Anaplastic thyroid tumor as an embolic source of metastasis. J. Vasc. Surg. Cases Innov. Tech., 2022; 8 (3): 386‒389. doi: 10.1016/j.jvscit.2022.05.006

44. Lioudaki S., Kontopodis N., Palioudakis S., Koutsopoulos A.V., Drositis I., Ioannou C.V. Acute aortic occlusion due to tumor embolism in a patient with lung malignancy. SAGE Open Med. Case Rep., 2017; 5: 2050313X17720627. doi: 10.1177/2050313X17720627

45. Almatari A.L., Sathe A., Wideman L., Dewan C.A., Vaughan J.P., Bennie I.C., Buscarini M. Renal cell carcinoma with tumor thrombus: A review of relevant anatomy and surgical techniques for the general urologist. Urol. Oncol., 2023; 41 (4): 153‒165. doi: 10.1016/j.urolonc.2022.11.021

46. Sadat U., Noor N., See T.C., Varty K. Peripheral arterial ischemia by a primary lung tumour invading left atrium. Lung Cancer, 2007; 57 (2): 237‒239. doi: 10.1016/j.lungcan.2007.02.001

47. Navi B.B., Reiner A.S., Kamel H., Iadecola C., Okin P.M., Tagawa S.T., Panageas K.S., DeAngelis L.M. Arterial thromboembolic events preceding the diagnosis of cancer in older persons. Blood, 2019; 133 (8): 781‒789. doi: 10.1182/blood-2018-06-860874

48. Yu J., Li A., Laureano M., Crowther M. Frequency of arterial thromboembolism in populations with malignancies: A systematic review. Thromb. Res., 2019; 184: 16‒23. doi: 10.1016/j.thromres.2019.10.004

49. Vavlukis M., Kotlar I., Chaparoska E., Antova E., Kedev S. Diffuse arterial thrombosis as a first manifestation of occult malignancy. Case Rep. Med., 2016; 2016: 1658392. doi: 10.1155/2016/1658392

50. Palumbo A., Cavo M., Bringhen S., Zamagni E., Romano A., Patriarca F., Rossi D., Gentilini F., Crippa C., Galli M., Nozzoli C., Ria R., Marasca R., Montefusco V., Baldini L., Elice F., Callea V., Pulini S., Carella A.M., Zambello R., Benevolo G., Magarotto V., Tacchetti P., Pescosta N., Cellini C., Polloni C., Evangelista A., Caravita T., Morabito F., Offidani M., Tosi P., Boccadoro M. 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 (8): 986‒993. doi: 10.1200/JCO.2010.31.6844

51. Landolfi R., Marchioli R., Kutti J., Gisslinger H., Tognoni G., Patrono C., Barbui T. European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N. Engl. J. Med., 2004; 350 (2): 114‒124. doi: 10.1056/NEJMoa035572

52. Xu Y., Mallity C., Collins E., Siegal D.M., Wang T.F., Carrier M. Anticoagulation for the prevention of arterial thromboembolism in cancer patients by primary tumor site: a systematic review and meta-analysis of randomized trials. Eur. Heart J. Cardiovasc. Pharmacother., 2025; 10 (8): 665‒675. doi: 10.1093/ehjcvp/pvae068

53. Xu Y., Cole K., Collins E., Moledina A., Mallity C., Carrier M. Anticoagulation for the prevention of arterial thrombosis in ambulatory cancer patients: systematic review and meta-analysis. JACC CardioOncol., 2023; 5 (4): 520‒532. doi: 10.1016/j.jaccao.2023.04.003

54. Lyon A.R., López-Fernández T., Couch L.S., Asteggiano R., Aznar M.C., Bergler-Klein J., Boriani G., Cardinale D., Cordoba R., Cosyns B., Cutter D.J., de Azambuja E., de Boer R.A., Dent S.F., Farmakis D., Gevaert S.A., Gorog D.A., Herrmann J., Lenihan D., Moslehi J., Moura B., Salinger S.S., Stephens R., Suter T.M., Szmit S., Tamargo J., Thavendiranathan P., Tocchetti C.G., van der Meer P., van der Pal H.J.H. ESC Scientific Document Group. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur. Heart. J., 2022; 43 (41): 4229‒4361. doi: 10.1093/eurheartj/ehac244

55. Gevaert S.A., Halvorsen S., Sinnaeve P.R., Sambola A., Gulati G., Lancellotti P., van der Meer P., Lyon A.R., Farmakis D., Lee G., Boriani G., Wechalekar A., Okines A., Asteggiano R. Evaluation and management of cancer patients presenting with acute cardiovascular disease: a Consensus Document of the Acute CardioVascular Care (ACVC) association and the ESC council of Cardio-Oncology-Part 1: acute coronary syndromes and acute pericardial diseases. Eur. Heart J. Acute Cardiovasc. Care, 2021; 10 (8): 947‒959. doi: 10.1093/ehjacc/zuab056

56. Harnarayan P., Islam S., Naraynsingh V. Arterial embolism in malignancy: the role of surgery. Ther. Clin. Risk Manag., 2021; 17: 635‒640. doi: 10.2147/TCRM.S308026

57. Hussain S.M.A. Lung cancer embolization causing acute limb ischemia: a case report. J. Med. Case Rep., 2023; 17 (1): 56. doi: 10.1186/s13256-023-03769-5

58. Sato A., Matsumoto A., Naruse S., Isono Y., Maeda Y., Yamada M., Ikeda T., Sasajima Y., Jinno H. Acute arterial occlusive disease due to tumor thrombus from lung metastasis of breast cancer with cartilaginous and osseous metaplasia: a case report. Surg. Case Rep., 2023; 9 (1): 13. doi: 10.1186/s40792023-01598-8

59. Tsubouchi K., Ibusuki R., Makisumi K., Okamoto H., Iwasaki T., Okamatsu Y., Inoue K., Harada T. Tumor embolism as a cause of renal artery occlusion and acute Kidney injury diagnosed and treated with endovascular intervention in a patient with mediastinal undifferentiated sarcoma. Intern. Med., 2021; 60 (12): 1907‒1910. doi: 10.2169/internalmedicine.6249-20

60. Aboyans V., Ricco J.B., Bartelink M.E.L., Björck M., Brodmann M., Cohnert T., Collet J.P., Czerny M., de Carlo M., Debus S., Espinola-Klein C., Kahan T., Kownator S., Mazzolai L., Naylor A.R., Roffi M., Röther J., Sprynger M., Tendera M., Tepe G., Venermo M., Vlachopoulos C., Desormais I. ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. Endorsed by: the European Stroke Organization (ESO). The task force for the diagnosis and treatment of peripheral arterial diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur. Heart J., 2018; 39 (9): 763‒816. doi: 10.1093/eurheartj/ehx095