Risk Factors in Cancer Patients


Cite item

Full Text

Abstract

Numerous studies in recent years have proven that the oncological process is an independent risk factor for thrombosis. For a long period of time and at the moment, research is continuing on the pathogenesis of a prothrombotic state in cancer patients. It was shown that the degree of risk is influenced by such indicators as the histological type of tumor, the stage of development of the disease, surgery, duration and type of anesthesia, chemotherapy, hormonal therapy, age, the presence of central venous catheters, immobilization, thrombophilia, history of thrombosis, infections. Thrombosis in cancer patients is triggered by thrombogenic factors associated with the tumor, patient-associated factors and environmental factors. The tumor cell affects the balance of hemostasis by releasing procoagulant substances, profibrinolytic, proproteolytic and proaggregant activity, expression of adhesion molecules, secretion of proinflammatory and proangiogenic cytokines; new participants in the process have also been identified. Studies have confirmed the fact that inflammation and thrombosis are inextricably linked with each other and play an important role in the progression of the disease and metastasis. All this opens up new horizons for the development of modern innovative strategies for treating cancer patients and increasing survival.

About the authors

Ekaterina V. Slukhanchuk

Petrovsky National Research Centre of Surgery

Email: beloborodova@rambler.ru
ORCID iD: 0000-0001-7441-2778
SPIN-code: 7423-8944

MD, PhD

Russian Federation, 2, Abrikosovsky pereulok, 119991, Moscow

Victoria O. Bitsadze

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: vikabits@mail.ru
ORCID iD: 0000-0001-8404-1042
SPIN-code: 5930-0859

MD, PhD, Professor

Russian Federation, 2, Abrikosovsky pereulok, 119991, Moscow

Anatoly G. Tyan

Petrovsky National Research Centre of Surgery

Email: tag-75@mail.ru
ORCID iD: 0000-0003-1659-4256
SPIN-code: 6960-9405

MD, PhD

Russian Federation, 2 Abrikosovsky pereulok, Moscow

Jamilya Kh. Khizroeva

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: jamatotu@gmail.com
ORCID iD: 0000-0002-0725-9686
SPIN-code: 8225-4976

MD, PhD, Professor

Russian Federation, 2, Abrikosovsky pereulok, 119991, Moscow

Maria V. Tretyakova

“Medical Center” LLC

Email: tretyakova777@yandex.ru
ORCID iD: 0000-0002-3628-0804
SPIN-code: 1463-0065

MD, PhD

Russian Federation, 2, Abrikosovsky pereulok, 119991, Moscow

Antonina G. Solopova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: antoninasolopova@yandex.ru
ORCID iD: 0000-0002-7456-2386
SPIN-code: 5278-0465
Scopus Author ID: 6505479504
ResearcherId: Q-1385-2015

MD, PhD, Professor

Russian Federation, 2, Abrikosovsky pereulok, 119991, Moscow

Meng Muyang

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: mmy88888@163.com
ORCID iD: 0000-0002-8326-556X

PhD Student

Russian Federation, 2, Abrikosovsky pereulok, 119991, Moscow

Ismail Elalamy

I.M. Sechenov First Moscow State Medical University (Sechenov University); Medicine Sorbonne University, Thrombosis Center, Tenon University Hospital

Email: ismail.elalamy@aphp.fr
ORCID iD: 0000-0002-9576-1368

MD, PhD, Professor

Russian Federation, 2, Abrikosovsky pereulok, 119991, Moscow; Paris (France)

Jean-Christophe Gris

I.M. Sechenov First Moscow State Medical University (Sechenov University); University Montpellier

Email: jean.christophe.gris@chu-nimes.fr
ORCID iD: 0000-0002-9899-9910
Scopus Author ID: 7005114260

MD, PhD, Professor

Russian Federation, 2, Abrikosovsky pereulok, 119991, Moscow; Montpellier (France)

Cihan Ay

I.M. Sechenov First Moscow State Medical University (Sechenov University); Medical University of Vienna

Author for correspondence.
Email: cihan.ay@hotmail.com
ORCID iD: 0000-0003-2607-9717

Department of Medicine, Clinical Division of Hematology and Hemostaseology, MD, Professor

Austria, 2, Abrikosovsky pereulok, 119991, Moscow; Vienna (Austria)

Aleksander D. Makatsaria

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: gemostasis@mail.ru
ORCID iD: 0000-0001-7415-4633
SPIN-code: 7538-2966
https://internist.ru/lectors/detail/makatsariya-/

MD, PhD, Professor, Academician of the RAS

Russian Federation, 2, Abrikosovsky pereulok, 119991, Moscow

References

  1. Wun T, White RH. Venous thromboembolism (VTE) in patients with cancer: epidemiology and risk factors. Cancer Invest. 2009;27 (Suppl 1):63–74. doi: https://doi.org/10.1080/07357900802656681
  2. O’Connell C, Razavi P, Ghalichi M, et al. Unsuspected pulmonary emboli adversely impact survival in patients with cancer undergoing routine staging multi‐row detector computed tomography scanning. J Thromb Haemost. 2011;9(2):305–311. doi: https://doi.org/10.1111/j.1538-7836.2010.04114.x
  3. Falanga A, Marchetti M. Venous thromboembolism in the hematologic malignancies. J Clin Oncol. 2009;27:4848–4857 doi: https://doi.org/10.1097/CCO.0b013e3283592331
  4. Noble S, Pasi J. Epidemiology and pathophysiology of cancer-associated thrombosis. Br J Cancer. 2010;102:S2–S9. doi: https://doi.org/10.1038/sj.bjc.6605599
  5. Chen N, Ren M, Li R, et al. Bevacizumab promotes venous thromboembolism through the induction of PAI-1 in a mouse xenograft model of human lung carcinoma. Mol Cancer. 2015;14:140. doi: https://doi.org/10.1186/s12943-015-0418-x
  6. Granger JM, Kontoyiannis DP. Etiology and outcome of extreme leukocytosis in 758 nonhematologic cancer patients: a retrospective, single‐institution study. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2009;115:3919–3923. doi: https://doi.org/10.1002/cncr.24480
  7. Blix K, Jensvoll H, Brækkan SK, Hansen J-B. White blood cell count measured prior to cancer development is associated with future risk of venous thromboembolism–the Tromsø study. PloS One. 2013;8:e73447. doi: https://doi.org/10.1371/journal.pone.0073447
  8. Kim J-E, Lee N, Gu J-Y, et al. Circulating levels of DNA-histone complex and dsDNA are independent prognostic factors of disseminated intravascular coagulation. Thromb Res. 2015;135:1064–1069. doi: https://doi.org/10.1016/j.thromres.2015.03.014
  9. Geddings JE, Hisada Y, Boulaftali Y, et al. Tissue factor–positive tumor microvesicles activate platelets and enhance thrombosis in mice. J Thromb Haemost. 2016;14:153–166. doi: https://doi.org/10.1111/jth.13181
  10. Gardiner C, Harrison P, Belting M, et al. Extracellular vesicles, tissue factor, cancer and thrombosis–discussion themes of the ISEV 2014 Educational Day. J Extracell Vesicles. 2015;4:26901. doi: https://doi.org/10.3402/jev.v4.26901
  11. Stark K, Schubert I, Joshi U, et al. Distinct pathogenesis of pancreatic cancer microvesicle-associated venous thrombosis identifies new antithrombotic targets in vivo. Arterioscler Thromb Vasc Biol. 2018;38:772–786. doi: https://doi.org/10.1161/ATVBAHA.117.310262
  12. Geddings JE, Mackman N. Tumor-derived tissue factor–positive microparticles and venous thrombosis in cancer patients. Blood. 2013;122:1873–1880. doi: https://doi.org/10.1182/blood-2013-04-460139
  13. Shindo K, Aishima S, Ohuchida K, et al. Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas. Mol Cancer. 2013;12:168. doi: https://doi.org/10.1186/1476-4598-12-168
  14. Gagliano N, Celesti G, Tacchini L, et al. Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma: Characterization in a 3D-cell culture model. World J Gastroenterol. 2016;22(18):4466–4483. doi: https://doi.org/10.3748/wjg.v22.i18.4466
  15. Payne H, Ponomaryov T, Watson SP, et al. Mice with a deficiency in CLEC-2 are protected against deep vein thrombosis. Blood. 2017;129:2013–2020. doi: https://doi.org/10.1182/blood-2016-09-742999
  16. Abdol Razak NB, Jones G, Bhandari M, et al. Cancer-associated thrombosis: An overview of mechanisms, risk factors, and treatment. Cancers. 2018;10:380. doi: https://doi.org/10.3390/cancers10100380
  17. Chrysanthopoulou A, Kambas K, Stakos D, et al. Interferon lambda1/IL‐29 and inorganic polyphosphate are novel regulators of neutrophil‐driven thromboinflammation. The Journal of Pathology. 2017;243:111–122. doi: https://doi.org/10.1002/path.4935
  18. Abdol Razak N, Elaskalani O, Metharom P. Pancreatic cancer-induced neutrophil extracellular traps: A potential contributor to cancer-associated thrombosis. Int J Mol Sci. 2017;18(3):487 doi: https://doi.org/10.3390/ijms18030487
  19. Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303:1532–1535. doi: https://doi.org/10.1126/science.1092385
  20. Von Brühl M-L, Stark K, Steinhart A, et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med. 2012;209(4):819–835. doi: https://doi.org/10.1084/jem.20112322
  21. Brill A, Fuchs T, Savchenko A, et al. Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost. 2012;10:136–144. doi: https://doi.org/10.1111/j.1538-7836.2011.04544.x
  22. Leal AC, Mizurini DM, Gomes T, et al. Tumor-derived exosomes induce the formation of neutrophil extracellular traps: Implications for the establishment of cancer-associated thrombosis. Sci Rep. 2017;7:1–12. doi: https://doi.org/10.1038/s41598-017-06893-7
  23. Brinkmann V. Neutrophil extracellular traps in the second decade. J Innate Immun. 2018;10:414–421. doi: https://doi.org/10.1159/000489829
  24. Lam FW, Cruz MA, Parikh K, et al. Histones stimulate von Willebrand factor release in vitro and in vivo. Haematologica. 2016;101:e277. doi: https://doi.org/10.3324/haematol.2015.140632
  25. McDonald B, Davis RP, Kim S-J, et al. Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood. 2017;129:1357–1367. doi: https://doi.org/10.1182/blood-2016-09-741298
  26. Fuchs TA, Brill A, Wagner DD. Neutrophil extracellular trap (NET) impact on deep vein thrombosis. Arterioscler Thromb Vasc Biol. 2012;32:1777–1783. doi: https://doi.org/10.1161/ATVBAHA.111.242859
  27. Mauracher LM, Posch F, Martinod K, et al. Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation, predicts the risk of venous thromboembolism in cancer patients. J Thromb Haemost. 2018;16:508–518. doi: https://doi.org/10.1111/jth.13951
  28. Wolach O, Sellar RS, Martinod K, et al. Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. Sci Transl Med. 2018;10(436):eaan8292. doi: https://doi.org/10.1126/scitranslmed.aan8292
  29. Schedel F, Mayer‐Hain S, Pappelbaum KI, et al. Evidence and impact of neutrophil extracellular traps in malignant melanoma. Pigment Cell Melanoma Res. 2020;33:63–73. doi: https://doi.org/10.1111/pcmr.12818
  30. Teijeira Á, Garasa S, Gato M, et al. Cxcr1 and cxcr2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity. Immunity. 2020. doi: https://doi.org/10.1016/j.immuni.2020.03.001
  31. Khizroeva J, Makatsariya A, Bitsadze V, et al. Laboratory monitoring of COVID-19 patients and importance of coagulopathy markers. Obstetrics, Gynecology and Reproduction. 2020;14:132–147. doi: https://doi.org/10.17749/2313-7347.141
  32. Yang L-Y, Luo Q, Lu L, et al. Increased neutrophil extracellular traps promote metastasis potential of hepatocellular carcinoma via provoking tumorous inflammatory response. Journal of Hematology & Oncology. 2020;13:1–15. doi: https://doi.org/10.1186/s13045-019-0836-0
  33. Makatsariya A, Slukhanchuk E, Bitsadze V, et al. COVID-19, neutrophil extracellular traps and vascular complications in obstetric practice. J Perinat Med. 2020;48(9):985-994. doi: https://doi.org/10.1515/jpm-2020-0280
  34. White C, Noble SI, Watson M, et al. Prevalence, symptom burden, and natural history of deep vein thrombosis in people with advanced cancer in specialist palliative care units (HIDDen): A prospective longitudinal observational study. Lancet Haematol. 2019;6:e79–e88. doi: https://doi.org/10.1016/S2352-3026(18)30215-1
  35. Grilz E, Mauracher LM, Posch F, et al. Citrullinated histone H3, a biomarker for neutrophil extracellular trap formation, predicts the risk of mortality in patients with cancer. Br J Haematol. 2019;186:311–320. doi: https://doi.org/10.1111/bjh.15906
  36. Meier TR, Myers Jr DD, Wrobleski SK, et al. Prophylactic P-selectin inhibition with PSI-421 promotes resolution of venous thrombosis without anticoagulation. Thromb Haemostas. 2008;99:343–351. doi: https://doi.org/10.1160/TH07-10-0608
  37. Ay C, Simanek R, Vormittag R, et al. High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: Results from the Vienna Cancer and Thrombosis Study (CATS). Blood. 2008;112:2703–2708. doi: https://doi.org/10.1182/blood-2008-02-142422
  38. Kaur S, Kumar S, Momi N, et al. Mucins in pancreatic cancer and its microenvironment. Nat Rev Gastroenterol Hepatol. 2013;10:607–620. doi: https://doi.org/10.1038/nrgastro.2013.120
  39. Shao B, Wahrenbrock MG, Yao L, et al. Carcinoma mucins trigger reciprocal activation of platelets and neutrophils in a murine model of Trousseau syndrome. Blood. 2011;118:4015–4023. doi: https://doi.org/10.1182/blood-2011-07-368514
  40. Muz B, de la Puente P, Azab F, et al. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia. 2015;3:83. doi: https://doi.org/10.2147/HP.S93413
  41. Di Virgilio F, Adinolfi E. Extracellular purines, purinergic receptors and tumor growth. Oncogene. 2017;36:293–303. doi: https://doi.org/10.1038/onc.2016.206
  42. Hernandez C, Huebener P, Schwabe RF. Damage-associated molecular patterns in cancer: a double-edged sword. Oncogene. 2016;35:5931–5941. doi: https://doi.org/10.1038/onc.2016.104
  43. Yang X, Wang H, Zhang M, et al. HMGB1: a novel protein that induced platelets active and aggregation via Toll-like receptor-4, NF-κB and cGMP dependent mechanisms. Diagn Pathol. 2015;10:134. doi: https://doi.org/10.1186/s13000-018-0747-3
  44. Tadie J-M, Bae H-B, Jiang S, et al. HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4. Am J Physiol Lung Cell Mol Physiol. 2013;304(5):L342–L349. doi: https://doi.org/10.1152/ajplung.00151.2012
  45. Khorana AA. The NCCN Clinical Practice Guidelines on Venous Thromboembolic Disease: Strategies for improving VTE prophylaxis in hospitalized cancer patients. Oncologist. 2007;12(11):1361–1370. doi: https://doi.org/10.1634/theoncologist.12-11-1361
  46. Lechner D, Kollars M, Gleiss A, et al. Chemotherapy‐induced thrombin generation via procoagulant endothelial microparticles is independent of tissue factor activity. J Thromb Haemost. 2007;5:2445–2452. doi: https://doi.org/10.1111/j.1538-7836.2007.02788.x
  47. Keefe D, Bowen J, Gibson R, et al. Noncardiac vascular toxicities of vascular endothelial growth factor inhibitors in advanced cancer: A review. Oncologist. 2011;16:432. doi: https://doi.org/10.1634/theoncologist.2010-0271
  48. Rugo HS, Herbst RS, Liu G, et al. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: Pharmacokinetic and clinical results. J Clin Oncol. 2005;23:5474–5483. doi: https://doi.org/10.1200/JCO.2005.04.192
  49. Choueiri TK, Schutz F, Je Y, et al. Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. J Clin Oncol. 2010;28(13):2280–2285. doi: https://doi.org/10.1200/JCO.2009.27.2757
  50. Bohlius J, Langensiepen S, Schwarzer G, et al. Recombinant human erythropoietin and overall survival in cancer patients: Results of a comprehensive meta-analysis. J Natl Cancer Inst. 2005;97(7):489–498. doi: https://doi.org/10.1093/jnci/dji087
  51. Shivakumar SP, Anderson DR, Couban S. Catheter-associated thrombosis in patients with malignancy. J Clin Oncol. 2009;27:4858–4864. doi: https://doi.org/10.1200/JCO.2009.22.6126
  52. Verso M, Agnelli G, Kamphuisen PW, et al. Risk factors for upper limb deep vein thrombosis associated with the use of central vein catheter in cancer patients. Intern Emerg Med. 2008;3(2):117–122. doi: https://doi.org/10.1007/s11739-008-0125-3
  53. Khorana AA, Dalal M, Lin J, et al. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high‐risk cancer patients undergoing chemotherapy in the United States. Cancer. 2013;119:648–655. doi: https://doi.org/10.1002/cncr.27772
  54. Khorana AA. Cancer and coagulation. Am J Hematol. 2012;87 (Suppl 1):S82–S87. doi: https://doi.org/10.1002/ajh.23143
  55. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902–4907. doi: https://doi.org/10.1182/blood.V104.11.2586.2586
  56. Khorana AA. Risk assessment and prophylaxis for VTE in cancer patients. J Natl Compr Canc Netw. 2011;9(7):789–797. doi: https://doi.org/10.1182/blood.V104.11.2586.2586
  57. Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010;116:5377–5382. doi: https://doi.org/10.1182/blood-2010-02-270116
  58. Khorana AA, Francis CW. Risk prediction of cancer-associated thrombosis: appraising the first decade and developing the future. Thromb Res. 2018;164:S70–S76. doi: https://doi.org/10.1016/j.thromres.2018.01.036
  59. Verso M, Agnelli G, Barni S, et al. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: The Protecht score. Intern Emerg Med. 2012;7:291. doi: https://doi.org/10.1007/s11739-012-0784-y
  60. Sohne M, Kruip M, Nijkeuter M, et al. Accuracy of clinical decision rule, D‐dimer and spiral computed tomography in patients with malignancy, previous venous thromboembolism, COPD or heart failure and in older patients with suspected pulmonary embolism. J Thromb Haemost. 2006;4:1042–1046. doi: https://doi.org/10.1007/s11739-012-0784-y
  61. Posch F, Riedl J, Reitter E-M, et al. Dynamic assessment of venous thromboembolism risk in patients with cancer by longitudinal D-Dimer analysis: A prospective study. J Thromb Haemost. 2020;18(6):1348–1356. doi: https://doi.org/10.1111/jth.14774

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig 1. Risk factors for thrombosis in cancer patients

Download (263KB)
Indexing metadata
3. Fig 2. Molecular mechanisms of tumor cell thrombogenesis: ATIII - antithrombin III; PrS - protein C; PrS - protein S; PAI-1 - plasminogen activator inhibitor 1; TF - tissue factor; PV - vilebrand factor; PLA2 - phospholipase A2; TAK - platelet-activating factor; CP - cysteine protease; ADP - adenosine diphosphate; NE, neutrophil elastase; citH3 - histone H3; cit H4 - histone H4; G - cathepsin G; PAD4 - peptidyl arginine deiminase 4; DAMPs - Molecular Fragments Associated with Damage

Download (404KB)
Indexing metadata

Copyright (c) 2021 "Paediatrician" Publishers LLC

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».