Русский
Prognostic role of thrombus formation biomarkers in thromboembolic complications diagnostics in patients with malignant neoplasms
DOI: https://dx.doi.org/10.18565/therapy.2022.8.54-61
Tarasova L.V., Dimitrieva O.V.
1) I.N. Ulyanov Chuvash State University, Cheboksary; 2) Surgut State University; 3) Institute for Advanced Medical Education of the Ministry of Healthcare of Chuvash Republic, Cheboksary; 4) Republican Clinical Hospital of the Ministry of Healthcare of the Chuvash Republic, Cheboksary; 5) Republican Cardiological Dispensary of the Ministry of Healthcare of the Chuvash Republic, Cheboksary
The aim of the study is to examine high-risk factors of VTEC development among malignant neoplasms patients using modern biomarkers.
Material and methods. A comparative analysis of the level of the cell adhesion marker P-selectin was carried out in 122 patients with pulmonary embolism (PE) having also malignant neoplasms who were hospitalized at Republican Cardiological Dispensary of the Ministry of Healthcare of the Chuvash Republic, and 89 outpatients with malignant neoplasms without PE at the basis of Republican Clinical Oncological Dispensary of the Ministry of Healthcare of Chuvash Republic.
Results. The leading risk factors for VTEC in patients with malignant neoplasms were: age over 57 years, a history of thromboembolic events, concomitant cardiac arrhythmias, localization of the oncological process (colorectal cancer, pancreatic cancer, combined cancers), size of the tumor process, the presence of regional and distant metastases, early onset of the disease (the first 3 months from the diagnosis of malignant neoplasm), fibrinogen levels >2,6 g/l, CRP >16,9 mg/l, hemoglobin <110 g/l, D-dimer >2,0 µg/ml, P-selectin >375,0 ng/ml.
Conclusion. Early detection of established risk factors for VTEC in malignant neoplasms patients will allow initiating primary VTEC prevention at the outpatient stage (prescription of oral anticoagulants). In patients with an intermediate risk of VTEC, when deciding on the appointment of anticoagulant therapy, as a clarifying laboratory method for detecting thrombotic readiness, in addition to determining the concentration of D-dimer in the blood serum, it is advisable to evaluate a new biomarker of cell adhesion – P-selectin.
Literature
1. Khorana A., Connolly G. Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol. 2009; 27(29): 4839–47. https://dx.doi.org/10.1200/JCO.2009.22.3271. 2. Abdol Razak N.B., Jones G., Bhandari M. et al. Cancer-associated thrombosis: An overview of mechanisms, risk factors, and treatment. Cancers (Basel). 2018; 10(10): 380. https://dx.doi.org/10.3390/cancers10100380. 3. Hindre R., Hamdan A., Pastre J. et al. [Treatment of cancer-associated thrombosis. Bull Cancer. 2022; 109(5): 528–36 (In French)]. https://dx.doi.org/10.1016/j.bulcan.2021.11.015. 4. Плохова Е.В., Дундуа Д.П. Проблема тромбоза у пациентов со злокачественными заболеваниями. Кардиология. 2018; 58(S9): 19–28. [Plokhova E.V., Dundua D.P. Thrombosis in patients with malignancy. Kardiologiya = Cardiology. 2018; 58(S9): 19–28 (In Russ.)]. https://dx.doi.org/10.18087/cardio.2523. EDN: YATIRF. 5. Пищулов К.А., Мельничникова О.С., Золотова Е.А. с соавт. Факторы риска венозных тромбоэмболических осложнений у пациентов с глиальными опухолями головного мозга. Российский журнал персонализированной медицины. 2021; 1(1): 192–206. [Pishchulov K.A., Melnichnikova O.S., Zolotova E.A. et al. Risk factors for venous thromboembolic in glioma patients. Russian Rossiyskiy zhurnal personalizirovannoy meditsiny = Journal for Personalized Medicine. 2021; 1(1): 192–206 (In Russ.)]. EDN: AOBXVS. 6. Lee A.Y.Y. Overview of VTE treatment in cancer according to clinical guidelines. Thromb Res. 2018; 164 Suppl 1: S162–S167.https://dx.doi.org/10.1016/j.thromres.2018.01.002. 7. Kim A.S., Khorana A.A., McCrae K.R. Mechanisms and biomarkers of cancer-associated thrombosis. Transl Res. 2020; 225: 33–53. https://dx.doi.org/10.1016/j.trsl.2020.06.012. 8. 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 thrombosis. Тerapiya = Therapy. 2021; 7(7): 132–137 (In Russ.)].https://dx.doi.org/10.18565/therapy.2021.7.132-137. EDN: GPFEZZ. 9. Chew H.K., 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. https://dx.doi.org/10.1001/archinte.166.4.458. 10. Blom J.W., Vanderschoot J.P.M., Oostindier M.J. 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; 4(3): 529–35. https://dx.doi.org/10.1111/j.1538-7836.2006.01804.x. 11. Chavakis T., Orlova V.V., Economopoulou M. et al. Junctional adhesion molecule-C regulates vascular endothelial permeability by modulating VE-cadherin-mediated cell-cell contacts. J Exp Med. 2006; 203(12): 2703–14. https://dx.doi.org/10.1084/jem.20051730. 12. van Gils J.M., Stutterheim J., van Duijn T.J. et al. HPA-1a alloantibodies reduce endothelial cell spreading and monolayer integrity. Mol Immunol. 2009; 46(3): 406–15. https://dx.doi.org/10.1016/j.molimm.2008.10.015. 13. Golias C., Batistatou A., Bablekos G. et al. Physiology and pathophysiology of selectins, integrins, and IgSF cell adhesion molecules focusing on inflammation. A paradigm model on infectious endocarditis. Cell Commun Adhes. 2011; 18(3): 19–32.https://dx.doi.org/10.3109/15419061.2011.606381. 14. Чуянова А.А., Понасенко А.В. Ассоциация полиморфизмов генов селектинов и эндотелина-1 с развитием тромбоэмболии легочной артерии. Сибирское медицинское обозрение. 2018; 4: 5–12. [Chuyanova A.A., Ponasenko A.V. Association of selectin genes polymorphisms and endotelin-1 with the development of pulmonary embolism. Sibirskoye meditsinskoye obozreniye = Siberian Medical Review. 2018; 4: 5–12 (In Russ.)]. https://dx.doi.org/10.20333/2500136-2018-4-5-12. EDN: XWPTNB. 15. Riva N., Vella K., Hickey K. et al. Biomarkers for the diagnosis of venous thromboembolism: D-dimer, thrombin generation, procoagulant phospholipid and soluble P-selectin. J Clin Pathol. 2018; 71(11): 1015–22. https://dx.doi.org/10.1136/jclinpath-2018-205293. 16. Ramacciotti E., Blackburn S., Hawley A.E. et al. Evaluation of soluble P-selectin as a marker for the diagnosis of deep venous thrombosis. Clin Appl Thromb Hemost. 2011; 17(4): 425–31. https://dx.doi.org/10.1177/1076029611405032. 17. Konstantinides S.V., Meyer G., Becattini C. et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020; 41(4): 543–603.https://dx.doi.org/10.1093/eurheartj/ehz405. 18. Khanna A.K., Vaidya M., Khanna S. Novel biomarkers in deep vein thrombosis. In: Khanna A., Jindal R. (eds). Venous disorders. Springer, Singapore. 2018; pp. 129–35. https://doi.org/10.1007/978-981-13-1108-6_12. Print ISBN: 978-981-13-1107-9. Online ISBN: 978-981-13-1108-6. 19. Jafari M., Sriram V., Xu Z. et al. Fucoidan-doxorubicin nanoparticles targeting P-selectin for effective breast cancer therapy. Carbohydr Polym. 2020; 249: 116837. https://dx.doi.org/10.1016/j.carbpol.2020.116837. 20. Myers D., Wrobleski S., Londy F. et al. New and effective treatment of experimentally induced venous thrombosis with anti-inflammatory rPSGL-Ig. Thrombosis and Haemostasis. 2002; 87(3): 374–82. 21. Myers D.D., Hawley A.E., Farris D.M. et al. P-selectin and leukocyte microparticles are associated with venous thrombogenesis. J Vasc Surg. 2003; 38(5): 1075–89. https://dx.doi.org/10.1016/S0741 5214(03)01033-4. 22. Bielinski S.J., Berardi C., Decker P.A. et al. P-selectin and subclinical and clinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2015; 240(1): 3–9. https://dx.doi.org/10.1016/j.atherosclerosis.2015.02.036. 23. Ridker P.M., Buring J.E., Rifai N. Soluble P-selectin and the risk of future cardiovascular events. Circulation. 2001; 103(4): 491–95. https://dx.doi.org/10.1161/01.cir.103.4.491. 24. Филатова А.Ю., Ромасов И.В., Потехина А.В. с соавт. Сроки возникновения и возможные предикторы коронарного рестеноза. Кардиология. 2020; 60(2): 10–16. [Filatova A.Yu., Romasov I.V., Potekhina A.V. et al. The incidence and possible predictors of coronary restenosis. Kardiologiya = Cardiology. 2020; 60(2): 10–16 (In Russ.)]. https://dx.doi.org/10.18087/cardio.2020.2.n621. EDN: RSWBAD. 25. Riva N., Bellesini M., Di Minno M.N. et al. Poor predictive value of contemporary bleeding risk scores during long-term treatment of venous thromboembolism. A multicentre retrospective cohort study. Thromb Haemost. 2014; 112(3): 511–21.https://dx.doi.org/10.1160/TH14-01-0081. 26. Ay C., Jungbauer L.V., Sailer T. et al. High concentrations of soluble P-selectin are associated with risk of venous thromboembolism and the P-selectin Thr715 variant. Clin Chem. 2007; 53(7): 1235–43. https://dx.doi.org/10.1373/clinchem.2006.085068. 27. Grilz E., Marosi C., Konigsbrugge O. et al. Association of complete blood count parameters, d-dimer, and soluble P-selectin with risk of arterial thromboembolism in patients with cancer. J Thromb Haemost. 2019; 17(8): 1335–44. https://dx.doi.org/10.1111/jth.14484. 28. Natoni A., Macauley M.S., O’Dwyer M.E. Targeting selectins and their ligands in cancer. Front Oncol. 2016; 6: 93.https://dx.doi.org/10.3389/fonc.2016.00093. 29. van Es N., Louzada M., Carrier M. et al. Predicting the risk of recurrent venous thromboembolism in patients with cancer:A prospective cohort study. Thromb Res. 2018; 163: 41–46. https://dx.doi.org/10.1016/j.thromres.2018.01.009.
About the Autors
Larisa V. Tarasova, Dr. med. habil., head of the Department of faculty and hospital therapy, I.N. Ulyanov Chuvash State University, professor of the Department of internal diseases of the Medical institute, Surgut State University, professor of the Department of public health and healthcare, Institute for Advanced Medical Education of the Ministry of Healthcare of Chuvash Republic. Address: 428015, Cheboksary, 45 Moskovsky Avenue. E-mail: tlarisagast18@mail.ru. ORCID: https://orcid.org/0000-0003-1496-0689
Olga V. Dimitrieva, assistant at the Department of faculty and hospital therapy, I.N. Ulyanov Chuvash State University, head of the Department of quality control and safety 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
Similar Articles
