Laboratory markers for the risk of pulmonary embolism development in patients with malignant neoplasms


DOI: https://dx.doi.org/10.18565/therapy.2023.7.102-109

Dimitrieva O.V., Tarasova L.V., Babokin V.E., Trofimov N.A.

1) I.N. Ulyanov Chuvash State University, Cheboksary; 2) Republican Cardiological Dispensary of the Ministry of Healthcare of the Chuvash Republic, Cheboksary; 3) Institute for Advanced Medical Education of the Ministry of Healthcare of the Chuvash Republic, Cheboksary; 4) Republican Clinical Hospital of the Ministry of Healthcare of the Chuvash Republic, Cheboksary; 5) Federal Center for Traumatology, Orthopedics and Endoprosthetics of the Ministry of Healthcare of Russia, Cheboksary; 6) Privolzhsky Research Medical University of the Ministry of Healthcare of Russia, Nizhny Novgorod
Abstract. Cancer-associated thrombosis affects the course, progression, and mortality of oncologic patients. Prognostication of thromboembolism probability in patients with malignant neoplasms (MN) remains to be a quite complicated task. Previously, we published the first results of a study that identified the most significant predictors of the risk of venous thromboembolic complications (VTEC) in malignant neoplasms patients that fit the criteria of the Khorana scale, and proved the role of D-dimer and sP-selectin in the development of cancer-associated thrombosis. In continuation of the work, we performed a search for risk factors of pulmonary embolism (PE) development in MN patients from the moderate-risk VTEC group to find further management tactics for this category of patients.
The aim: to study laboratory markers of the risk of developing PE in patients with malignant neoplasms from the group of moderate risk of developing VTEC in order to improve VTEC prognostication.
Material and methods. A cohort study with a prospective cohort was performed. In the course of this study, the data of laboratory assessments were evaluated: D-dimer, sP-selectin and their combined use in outpatients with malignant neoplasms from the group of moderate risk of VTEC developing. Results. The study revealed threshold levels of D-dimer and sP-selectin as predictors of the development of PE in patients with malignant neoplasms. With a combined excess of the threshold value of D-dimer (>1,73 μg/ml) and sP-selectin (>309,4 ng/ml), the incidence of PE in MN patients from the moderate risk group according to Khorana scale increases to 95,1% (px2 <0,001; RR 2,72; CI: 2,14–3,46).
Conclusion. Obtained results allow us to improve patient stratification by including biomarkers in multivariate predictive models for personalized VTEC risk assessment, which will contribute to the decision to start anticoagulant therapy of MN patients from the moderate risk group according to the Khorana scale.
Keywords: sP-selectin, cancer-associated thrombosis, pulmonary embolism, D-dimer, thromboembolic complications
Read entire article

Literature

1. Сушинская Т.В., Стуклов Н.И., Доброхотова Ю.Э. Гемостаз и рак-ассоциированный тромбоз: современная профилактика и лечение. Онкология. Журнал им. П.А. Герцена. 2018; 7(4): 64–72. [Sushinskaya T.V., Stuklov N.I., Dobrokhotova Yu.E. Hemostasis and cancer-associated thrombosis: modern prevention and treatment. Onkologiya. Zhurnal imeni P.A. Gertsena = P.A. Herzen Journal of Oncology. 2018; 7(4): 64–72 (In Russ.)]. https://dx.doi.org/10.17116/onkolog20187464.


2. Donnellan E., Khorana AA. Cancer and venous thromboembolic disease: A review. Oncologist. 2017; 22(2): 199–207. https://dx.doi.org/10.1634/theoncologist.2016-0214.


3. Agnelli G., Verso M. Thromboprophylaxis during chemotherapy in patients with advanced cancer. Thromb Res. 2010; 125 Suppl 2: 17–20. https://dx.doi.org/10.1016/S 0049-3848(10)70007-4.


4. Figueredo V.M., Pressman G.S., Romero-Corral A. et al. Improvement in left ventricular systolic and diastolic performance during ranolazine treatment in patients with stable angina. J Cardiovasc Pharmacol Ther. J Cardiovasc Pharmacol Ther. 2011; 16(2): 168–72. https://dx.doi.org/10.1177/1074248410382105.


5. Robin P., Carrier M. Revisiting occult cancer screening in patients with unprovoked venous thromboembolism. Thromb Res. 2018; 164(1): 7–11. https://dx.doi.org/10.1016/j.thromres.2017.12.024.


6. Lubetsky A. Pulmonary embolism in cancer patients: A review. Isr Med Assoc J. 2022; 24(3): 179–82.


7. Heit J.A., Silverstein M.D., Mohr D.N. et al. Risk factors for deep vein thrombosis and pulmonary embolism: A population-based case- control study. Arch Intern Med. 2000; 160(6): 809–15. https://dx.doi.org/10.1001/archinte.160.6.809.


8. Ройтман Е.В. Основы профилактики венозных тромбоэмболических осложнений в онкологии. Учебное пособие. М.: Издательство РАМН. 2016; 83 с. [Roitman E.V. Fundamentals of prevention of venous thromboembolic complications in oncology. Tutorial. Moscow: RAMS Publishing House. 2016; 83 pp. (In Russ.)]. ISBN: 978-5-600-01676-7.


9. Ashrani A.A., Marks R.S., Petterson T.M. et al. Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: A population-based cohort study. Blood. 2014; 123(25): 3972–78. https://dx.doi.org/10.1182/blood-2014-01-549733.


10. Walker A.J., Card T.R., 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. https://dx.doi.org/10.1016/j.ejca.2012.10.021.


11. Konigsbrugge 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 Suppl 2: S39–43. https://dx.doi.org/10.1016/S0049-3848(14)50007-2.


12. Lan Y., Guan J., Zhu J. et al. Venous thromboembolic events in T-cell lymphoma patients: Incidence, risk factors and clinical features. Leuk Res. 2021; 103: 106537. https://dx.doi.org/10.1016/j.leukres.2021.106537.


13. Кательницкая О.В., Кит О.И., Кательницкий И.И. Особенности антикоагулянтной терапии венозных тромбоэмболических осложнений у пациентов со злокачественными новообразованиями. Флебология. 2020; 14(2): 135–141. [Katelnitskaya O.V., Kit O.I., Katelnitsky I.I. et al. Features of anticoagulant therapy of venous thromboembolism in patients with cancer. Flebologiya = Phlebology. 2020; 14(2): 135–141 (In Russ.)]. https://dx.doi.org/10.17116/flebo202014021135. EDN: UIYUVX.


14. Mulder F.I., Candeloro M., Kamphuisen P.W. et al.; CAT-prediction collaborators. The Khorana Score for prediction of venous thromboembolism in cancer patients: A systematic review and meta-analysis. Haematologica. 2019; 104(6): 1277–87. https://dx.doi.org/10.3324/haematol.2018.209114.


15. Timp J.F., Braekkan S.K., Versteeg H.H., Cannegieter S.C. Epidemiology of cancer-associated venous thrombosis. Blood. 2013; 122(10): 1712–23. https://dx.doi.org/10.1182/blood-2013-04-460121.


16. Lyman G.H., Carrier M., Ay C. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv. 2021; 5(4): 927–74. https://dx.doi.org/10.1182/bloodadvances.2020003442.


17. Konstantinides S.V. Chronic thromboembolic disease following pulmonary embolism: More work ahead. Eur Respir J. 2020; 55(4): 2000229. https://dx.doi.org/10.1183/13993003.00229-2020.


18. Falanga A., Brenner B., Khorana A.A., Francis C.W. Thrombotic complications in patients with cancer: Advances in pathogenesis, prevention, and treatment – A report from ICTHIC 2021. Res Pract Thromb Haemost. 2022; 6(5): e12744. https://dx.doi.org/10.1002/rth2.12744.


19. Khorana A.A., Kuderer N.M., Culakova E. et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008; 111(10): 4902–7. https://dx.doi.org/10.1182/blood-2007-10-116327.


20. Тарасова Л.В., Димитриева О.В., Долгов И.Ю., Эльмурзаева А.А. Модели определения рисков канцер-ассоциированных тромбозов. Терапия. 2021; 7(7): 132–137. [Tarasova L.V., Dimitrieva O.V., Dolgov I.Yu., Elmurzayeva A.A. Models of risk determination of cancer-associated thromboses. Terapiya = Therapy. 2021; 7(7): 132–137 (In Russ.)]. https://dx.doi.org/10.18565/therapy.2021.7.132-137. EDN GPFEZZ.


21. Тарасова Л.В., Димитриева О.В. Прогностическая роль биомаркеров тромбообразования в диагностике тромбоэмболических осложнений у пациентов со злокачественными новообразованиями. Терапия. 2022; 8(8): 54–61. [Tarasova L.V., Dimitrieva O.V. Prognostic role of thrombus formation biomarkers in thromboembolic complications diagnostics in patients with malignant neoplasms. Terapiya = Therapy. 2022; 8(8): 54–61 (In Russ.)]. https://dx.doi.org/10.18565/therapy.2022.8.54-61. EDN: UXZAEY.


22. Бокерия Л.А., Затевахин И.И., Кириенко А.И. с соавт. Российские клинические рекомендации по диагностике, лечению и профилактике венозных тромбоэмболических осложнений (ВТЭО). Флебология. 2015; 9(4–2): 1–52. [Bokeria L.A., Zatevakhin I.I., Kirienko A.I. et al. Russian clinical guidelines for the diagnosis, treatment and prevention of venous thromboembolic complications. Flebologiya = Phlebology. 2015; 9(4–2): 1–52 (In Russ.)]. EDN: XIOPYZ.


23. Konstantinides S.V., Meyer G., Becattini C. et al. The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Respir J. 2019; 54(3): 1901647. https://dx.doi.org/10.1183/13993003.01647-2019.


24. Вереина Н.К., Агасян Д.Г., Чулков В.С. Риск венозных тромбоэмболических осложнений у пациентов с хронической сердечной недостаточностью. Российский кардиологический журнал. 2020; 25(1): 9–13. [Vereina N.K., Agasyan D.G., Chulkov V.S. The risk of venous thromboembolism in patients with heart failure. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2020; 25(1): 9–13 (In Russ.)]. https://dx.doi.org/10.15829/1560-4071-2020-1-3678. EDN: MIQSET.


25. Tirandi A., Preda A., Carbone F. et al. Pulmonary embolism in patients with cancer: An updated and operative guide for diagnosis and management. Int J Cardiol. 2022; 358: 95–102. https://dx.doi.org/10.1016/j.ijcard.2022.04.068.


26. Вавилова Т.В., Соловьева Л.В., Бекоева А.Б. с соавт. Лучшие практики Российской Федерации в организации антикоагулянтной терапии у больных высокого риска тромбоэмболических осложнений. Российский кардиологический журнал. 2020; 25(6): 10–14. [Vavilova T.V., Solovyova L.V., Bekoeva A.B. et al. The best practices of the russian federation in the organization of anticoagulant therapy in patients with high risk of thromboembolic events. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2020; 25(6): 10–14 (In Russ.)]. https://dx.doi.org/10.15829/1560-4071-2020-3945. EDN: FHXNYJ.


27. Tieken C., Versteeg H.H. Anticoagulants versus cancer. Thromb Res. 2016; 140 Suppl 1: S148–53. https://dx.doi.org/10.1016/S0049-3848(16)30114-1.


28. Fei X., Wang H., Yuan W. et al. Tissue factor pathway inhibitor-1 is a valuable marker for the prediction of deep venous thrombosis and tumor metastasis in patients with lung cancer. Biomed Res Int. 2017; 2017: 8983763. https://dx.doi.org/10.1155/2017/8983763.


29. Li W., Tang Y., Song Y. et al. Prognostic role of pretreatment plasma D-dimer in patients with solid tumors: A systematic review and meta-analysis. Cell Physiol Biochem. 2018; 45(4): 1663–76. https://dx.doi.org/10.1159/000487734.


30. Yeini E., Ofek P., Pozzi S. et al. P-selectin axis plays a key role in microglia immunophenotype and glioblastoma progression. Nat Commun. 2021; 12(1): 1912. https://dx.doi.org/10.1038/s41467-021-22186-0.


31. Antonopoulos C.N., Sfyroeras G.S., Kakisis J.D. et al. The role of soluble P selectin in the diagnosis of venous thromboembolism. Thromb. Res. 2014; 133(1): 17–24. https://dx.doi.org/10.1016/j.thromres.2013.08.014.


32. Setiawan B., Budianto W., Sukarnowati T.W. et al. Correlation of inflammation and coagulation markers with the incidence of deep vein thrombosis in cancer patients with high risk of thrombosis. Int J Gen Med. 2022; 15: 6215–26. https://dx.doi.org/10.2147/IJGM.S372038.


About the Autors

Olga V. Dimitrieva, assistant at the Department of hospital therapy, I.N. Ulyanov Chuvash State University, head of the Department of quality and safety control of medical activities, Republican Cardiological Dispensary of the Ministry of Healthcare of the Chuvash Republic. Address: 428000, Cheboksary, 29A Fedora Gladkova Str.
E-mail: salgarii@mail.ru ORCID: https://orcid.org/0000-0002-7771-6141
Larisa V. Tarasova, MD, head of the Department of hospital therapy, I.N. Ulyanov Chuvash State University, professor of the Department of public health and healthcare, Institute for Advanced Medical Education of the Ministry of Healthcare of the Chuvash Republic. Address: 428015, Cheboksary, 45 Moskovsky Avenue.
E-mail: tlarisagast18@mail.ru ORCID: https://orcid.org/0000-0003-1496-0689
Vadim E. Babokin, MD, head of the Department of surgical diseases, I.N. Ulyanov Chuvash State University, professor of the Department of surgery, Institute for Advanced Medical Education of the Ministry of Healthcare of the Chuvash Republic, chief physician of Republican Cardiological Dispensary of the Ministry of Healthcare of the Chuvash Republic. Address: 428020, Cheboksary, 29A F. Gladkova Str.
E-mail: babokin@bk.ru ORCID: https://orcid.org/0000-0002-2788-8762
Nikolay A. Trofimov, MD., associate professor of the Department of surgical diseases and general surgery,
I.N. Ulyanov Chuvash State University, professor of the Department of surgery, Institute for Advanced Medical Education of the Ministry of Healthcare of the Chuvash Republic, deputy chief doctor for surgery of Republican Cardiological Dispensary of the Ministry of Healthcare of the Chuvash Republic. Address: 428020, Cheboksary, 29A F. Gladkova Str.
E-mail: nikolai.trofimov@mail.ru ORCID: https://orcid.org/0000-0002-1975-5521


Similar Articles

Back to Content

Бионика Медиа