Haemostasis and metastasis: anticoagulants therapeutic potential in ovarian cancer
https://doi.org/10.17749/2313-7347/ob.gyn.rep.2025.644
Abstract
Aim: to perform a comparative analysis of epithelial ovarian cancer (ОС) recurrence rate in patients with/without long-term anticoagulant therapy (АСТ) as a part of secondary prevention of thrombotic complications.
Materials and Methods. A prospective interventional non-randomized comparative study was conducted with 126 stage III–IV epithelial ОС patients. Main group patients (n = 66) received long-term АСТ (60–72 months) for secondary prevention of venous thromboembolic complications, while comparison group patients (n = 60) received no АСТ. Both groups were comparable in patient age, disease stage and amount of anticoagulant treatment. There were used direct oral anticoagulants: dabigatran, rivaroxaban and apixaban. ОС recurrence and thrombotic complications rate were assessed.
Results. OC recurrence rate was found to be 31.8 % (n = 21) in main group and 65 % (n = 39) in comparison group (p < 0.05). The incidence of thrombotic complications was comparable between groups: 18.2 % versus 16.7 % respectively. The data show a significant decline in OC recurrence risk upon long-term АСТ.
Conclusion. Long-term АСТ in patients with epithelial OC to prevent recurrent thrombosis may exert additional antitumour effect. The observed decline in OC recurrence rate supports the hypothesis that the haemostatic system is involved in the mechanisms of tumour invasion and metastasis. Further randomized trials are needed to evaluate efficacy of anticoagulants as potential modifiers of malignant neoplasm progression.
Keywords
About the Authors
A. V. VorobevRussian Federation
Alexander V. Vorobev - MD, PhD. Scopus Author ID: 57191966265. Wos ResearcherID: F-8804-2017.
8 bldg. 2, Trubetskaya Str., Moscow 119048
V. O. Bitsadze
Russian Federation
Victoria O. Bitsadze - MD, Dr Sci Med, Prof., Professor RAS. Scopus Author ID: 6506003478. WoS ResearcherID: F-8409-2017.
8 bldg. 2, Trubetskaya Str., Moscow 119048
J. Kh. Khizroeva
Russian Federation
Хизроева Джамиля Хизриевна - д.м.н., проф. Scopus Author ID: 57194547147. WoS ResearcherID: F-8384-2017.
8 bldg. 2, Trubetskaya Str., Moscow 119048
A. G. Solopova
Russian Federation
Antonina G. Solopova - MD, Dr Sci Med, Prof. Scopus Author ID: 6505479504. WoS ResearcherID: Q-1385-2015.
8 bldg. 2, Trubetskaya Str., Moscow 119048
D. M. Mamchich
Russian Federation
Daria M. Mamchich
8 bldg. 2, Trubetskaya Str., Moscow 119048
E. D. Mun
Russian Federation
Emma D. Mun
1 Ostrovityanovа Str., Moscow, 117513
D. V. Blinov
Russian Federation
Dmitry V. Blinov - MD, PhD, MBA. Scopus Author ID: 6701744871. WoS ResearcherID: E-8906-2017.
11–13/1 Lyalin Pereulok, Moscow 101000; 5 bldg. 1–1a, 2-ya Brestskaya Str., Moscow 123056; 6 bldg. 1, Rodnikovaya Str., Village Goluboe, Moscow region 141551
Jean-Christophe Gris
France
Jean-Christophe Gris - MD, Dr Sci Med, Prof. Scopus Author ID: 7005114260. WoS ResearcherID: AAA-2923-2019.
8 bldg. 2, Trubetskaya Str., Moscow 119048; 163 Rue Auguste Broussonnet, Montpellier 34090
I. Elalamy
France
Ismail Elalamy - MD, Dr Sci Med, Prof. Scopus Author ID: 7003652413. WoS ResearcherID: AAC-9695-2019
8 bldg. 2, Trubetskaya Str., Moscow 119048; 12 Rue de l’École de Médecine, Paris 75006; 4 Rue de la Chine, Paris 75020
G. Gerotziafas
France
Grigoriоs Gerotziafas - MD, Dr Sci Med, Prof.
8 bldg. 2, Trubetskaya Str., Moscow 119048; 12 Rue de l’École de Médecine, Paris 75006; 4 Rue de la Chine, Paris 75020
P. Van Dreden
France
Patrick Van Dreden - MD, Dr Sci Med, Prof. Scopus Author ID: 55915955300.
8 bldg. 2, Trubetskaya Str., Moscow 119048; 12 Rue de l’École de Médecine, Paris 75006
A. D. Makatsariya
Russian Federation
Alexander D. Makatsariya - MD, Dr Sci Med, Prof., Academician of RAS. Scopus Author ID: 57222220144. WoS ResearcherID: M-5660-2016.
8 bldg. 2, Trubetskaya Str., Moscow 119048
References
1. Sung H., Ferlay J., Siegel R.L. at al. Global Cancer Statistics 2020: GLOBOCAN Estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660.
2. Bredikhin R.A., Akhmetzyanov R.V., Khayrullin R.N. Expanding the possibilities of treatment and prevention of venous thromboembolic complications in cancer patients. The role of oral anticoagulants. [Rasshirenie vozmozhnostej lecheniya i profilaktiki venoznyh tromboembolicheskih oslozhnenij u pacientov s onkologicheskimi zabolevaniyami. Rol' peroral'nyh antikoagulyantov]. Klinitsist. 2022;16(2):17–26. (In Russ.). https://doi.org/10.17650/1818-8338-2022-16-2-К667.
3. Mulder F.I., Horváth-Puhó E., van Es N. et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood. 2021;137(14):1959–69. https://doi.org/10.1182/blood.2020007338.
4. Streiff M.B. Thrombosis in the setting of cancer. Hematology Am Soc Hematol Educ Program. 2016;2016(1):196–205. https://doi.org/10.1182/asheducation-2016.1.196.
5. Guo J., Gao Y., Gong Z. et al. Plasma D-dimer level correlates with age, metastasis, recurrence, tumor-node-metastasis classification (TNM), and treatment of non-small-cell lung cancer (NSCLC) patients. Biomed Res Int. 2021;2021:9623571. https://doi.org/10.1155/2021/9623571.
6. Hisada Y., Mackman N. Tissue factor and cancer: regulation, tumor growth and metastasis. Semin Thromb Hemost. 2019;45(4):385–95. https://doi.org/10.1055/s-0039-1687894.
7. Zhao B., Wu M., Hu Z. et al. A novel oncotherapy strategy: direct thrombin inhibitors suppress progression, dissemination and spontaneous metastasis in non-small cell lung cancer. Br J Pharmacol. 2022;179(22):5056–73. https://doi.org/10.1111/bph.15384.
8. Hisada Y., Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood. 2017;130(13):1499–506. https://doi.org/10.1182/blood-2017-03-743211.
9. Slukhanchuk E.V., Bitsadze V.O., Khizroeva J.Kh. et al. Platelets, thrombo-inflammation and cancer. [Trombocity, trombovospalenie i onkologicheskij process]. Obstetrics, Gynecology and Reproduction. 2021;15(6):755–76. (In Russ.). https://doi.org/10.17749/2313-7347/ob.gyn.rep.2021.274.
10. Stone R.L., Nick A.M., McNeish I.A. et al. Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med. 2012;366(7):610–8. https://doi.org/10.1056/NEJMoa1110352.
11. Zhou L., Zhang Z., Tian Y. et al. The critical role of platelet in cancer progression and metastasis. Eur J Med Res. 2023;28(1):385. https://doi.org/10.1186/s40001-023-01342-w.
12. Miyazaki M., Nakabo A., Nagano Y. et al. Tissue factor-induced fibrinogenesis mediates cancer cell clustering and multiclonal peritoneal metastasis. Cancer Lett. 2023;553:215983. https://doi.org/10.1016/j.canlet.2022.215983.
13. Cohen A.T., Hamilton M., Mitchell S.A. et al. Comparison of the novel oral anticoagulants apixaban, dabigatran, edoxaban, and rivaroxaban in the initial and long-term treatment and prevention of venous thromboembolism: systematic review and network meta-analysis. PLoS One. 2015;10(12):e0144856. https://doi.org/10.1371/journal.pone.0144856.
14. Farge D., Frere C., Connors J.M. et al.; International Initiative on Thrombosis and Cancer (ITAC) advisory panel. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncol. 2022;23(7):e334–e347. https://doi.org/10.1016/S1470-2045(22)00160-7.
15. Key N.S., Khorana A.A., Kuderer N.M. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO Guideline Update. J Clin Oncol. 2023;41(16):3063–71. https://doi.org/10.1200/JCO.23.00294.
16. Kurube I., Ambari E., Iskandar T. et al. Factors associated with recurrence of epithelial ovarian cancer In RSUP Dr. Kariadi Semarang. DIMJ. 2022;3(2):74–80. https://doi.org/10.14710/dimj.v3i2.15448.
17. Joy J., Kumar J., Kumar S., Arshad M. Clinical profiles and survival outcomes of patients with relapsed ovarian cancer: a single-center study. Cureus. 2024;16(11):e74724. https://doi.org/10.7759/cureus.74724.
18. Al-Azzawi H.M.A., Hamza S.A., Paolini R. et al. Towards an emerging role for anticoagulants in cancer therapy: a systematic review and meta-analysis. Front Oral Health. 2024;5:1495942. https://doi.org/10.3389/froh.2024.1495942.
19. Najidh S., Versteeg H.H., Buijs J.T. A systematic review on the effects of direct oral anticoagulants on cancer growth and metastasis in animal models. Thromb Res. 2020;187:18–27. https://doi.org/10.1016/j.thromres.2019.12.022.
Review
For citations:
Vorobev A.V., Bitsadze V.O., Khizroeva J.Kh., Solopova A.G., Mamchich D.M., Mun E.D., Blinov D.V., Gris J., Elalamy I., Gerotziafas G., Van Dreden P., Makatsariya A.D. Haemostasis and metastasis: anticoagulants therapeutic potential in ovarian cancer. Obstetrics, Gynecology and Reproduction. 2025;19(3):351-359. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2025.644

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.