O.V. Somonova – Dr. Sc. (Med.), Professor, Department of Clinical Biochemistry and Laboratory Diagnostics, A.I. Evdokimova Moscow State Medical and Dental University
S.L. Teodorovich – oncologist, N.N. Blokhin National Medical Research Center of Oncology (Moscow)
A.L. Elizarova – Ph.D. (Biol.), Senior Research Scientist, N.N. Blokhin National Medical Research Center of Oncology (Moscow)
N.E. Kushlinskii – Ph.D. (Med.), Professor, Corresponding member of RAS, Head of the Department of Clinical Biochemistry and Laboratory Diagnostics, A.I. Evdokimov Moscow State Medical and Dental University
Cancer patients are at high risk of thrombotic complications that worsen the outcome of antitumor treatment and occupy one of the leading places among the causes of death. Thrombosis in an oncologic patient increases the risk of death by 30 times, which is associated with the development of fatal thromboembolism and a more aggressive course of the tumor process. The leading role in the pathogenesis of thrombotic complications is played by abnormalities in the hemostasis system, caused both by the tumor itself and by treatment methods. Currently, low molecular weight heparins (LMWH) are the main drugs in the prevention and treatment of thrombotic complications in cancer patients. The effect of sodium dalteparin (fragmin) on the hemostatic system and the frequency of thrombotic complications in 60 patients with metastatic kidney cancer receiving immunotherapy was studied. The use of dalteparin sodium on the background of immunotherapy reduces the intensity of intravascular coagulation and the frequency of venous thrombosis. In the group of patients who did not receive medical prophylaxis, the incidence of complications was 6 (20%) cases, in the group of patients who received low molecular weight heparins – 1 (3%) cases (p<0.05). In N.N.Blokhin NMRC of Oncology conducted the first randomized study of the effectiveness of the combination of LMWH and immunotherapy in comparison with a single immunotherapy in patients with metastatic kidney cancer and hypercoagulation (Tsimafeyeu I.V. et al., 2009). The results of the studies showed that the median of tumor-specific survival in the group of patients who received fragmin against immunotherapy was 16.5 months [95% CI 12-21 months] versus 9 months [95% CI 7-12 months] in the group of patients who received only immunotherapy (p=0.019). Control of the disease (objective response + stabilization) in the group with fragmin was achieved more often than in patients who received only immunotherapy. The effect of therapy (objective response + partial response) was observed in 75% of patients in group I compared with 35% of patients in the control group (p=0.002).
- Agnelli G., Verso M. Management of venous thromboembolism in patients with cancer // J. Tromb. Haemost. 2011. V. 9. Suppl. 1. P. 316–324.
- Barsam S.J., Patel R., Arya R. Anticoagulation for prevention and treatment of cancer-related venous thromboembolism // Br. J. Haematol. 2013. V. 161, Is. 6. P. 764–777.
- Wun T., White R.H. Epidemiology of cancer-related venous thromboembolism // Best Pract. Res. Clin. Haemotol. 2009. V. 22. № 1. P. 9–23.
- Shaib W., Deng Y., Zilterman D., Lundberg B., Saif M.W. Assessing risk and mortality of venous thromboembolism in pancreatic cancer patients // Anticancer Res. 2010. V. 30. № 10. P. 4261–4264.
- Agnelli G., Verso M. Management of venous thromboembolism in patients with cancer // J. Thromb. Haemost. 2014. V. 9. Suppl 1. P. 316–324.
- Ogren M., Bergqvist D., Wahlander K., Eriksson H., Sternby N.H. Trousseaus syndrome – what is the evidence? A population – based autopsy study // Thromb. Haemost. 2006. V. 95. № 3. P. 541–545.
- Robin P., Carrier M. Revisiting occult cancer screening in patients with unprovoked venous thromboembolism // Thromb. Res. 2018. V. 164. Suppl 1. P. 7–11.
- Magnus N., D’Asti E., Meehan B., Garnier D., Rak J. Oncogenes and the coagulation system – forses that modulate dormant and aggressive states in cancer // Thromb. Res. 2014. V. 133. Suppl. 2. P. 1–9.
- Falanga A., Marchetti M. Hemostatic biomarkers in cancer progression // Thromb. Res. 2018. V. 164. Suppl. 1. P. 54–61.
- Cedervall J., Hamidi A., Olsson A.-K. Platelets, NETs and cancer // Thromb. Res. 2018. V. 164. Suppl. 1. P. 148–152.
- Mir Seyed Nazari P., Riedl J., Pabinger I., Ay C. The role of pododlanin in cancer-associated thrombosis // Thromb. Res. 2018. V. 164. Suppl. 1. P. 34–39.
- Cate H., Falanga A. Overview of the postulated mechanisms linking cancer and thrombosis // Pathophysiol. Haemost. Thromb. 2007. V. 36. № 3–4. P. 122–130.
- Agnelii G., Verso M. Thromboprophylaxis during chemotherapy in patients with advanced cancer // Thromb. Res. 2010. V. 125. Suppl. 2. P. 17–20.
- ZHernov A.A., Kachmazov A.A., Perepechin D.V. Profilaktika trombogennyh oslozhnenij v onkourologii // Eksperimental'naya klinicheskaya urologiya. 2010. № 3. S. 154–158.
- Timofeev I.V., Demidov L.V., Madzhuga A.V., Somonova O.V., Elizarova A.L. Nizkomolekulyarnyj geparin v kombinacii s immunoterapiej v lechenii metastaticheskogo pochechno-kletochnogo raka // Rossijskij onkologicheskij zhurnal. 2008. № 5. S. 27–30.
- Levine M.N., Lee A.Y., Kakkar A.K. Thrombosis and cancer. American Society of Clinical Oncology, 41 Annual Meeting. 2005. May 13–17. P. 748–577.
- Lee A.Y. The roles of anticoagulants in patients with cancer // Thromb. Res. 2010. V. 125. Suppl. 2. P. 8–11.
- Watson H.G., Keeling D.M., Laffan M., Tait R.C., Makris M. British Committee for Standards in Haematology. Guideline on aspects of cancer-related venous thrombosis // Brit. J. Haematol. 2015. V. 170. № 5. P. 640–648.
- Khorana A., Carrier M., Garcia D., Lee A.Y. Guidance for the prevention and treatment of cancer-associated venous thromboembolism // J. Thromb. Thrombolysis. 2016. V. 41. № 1. P. 81–91.
- Gran O.V., Braekhan S.K., Hansen J.B. Protrombotic genotypes and risk of venous thromboembolism in cancer // Thromb. Res. 2018. V. 164. Suppl. 1. P. 12–18.
- Timp J.F., Braekhan S.K., Versteeg H.H., Cannegieter S.C. Epidemiology of cancer-associated venous thrombosis // Blood. 2013. V. 122. № 10. P. 1712–1723.
- Franchini M., Bonfanti C., Lippi G. Cancer-associated thrombosis: investigating the role of new oral anticoagulants // Thromb. Res. 2015. V. 135. № 5. P. 777–781.
- Hirsh J., Warkentin T.E., Shaughnessy S.G., Anand S.S., Halperin J.L., Raschke R., Granger C., Ohman E.M., Dalen J.E. Heparin and low molecular weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy and safety // Chest. 2001. V. 119. Suppl. 1. 64S–94S.
- Somonova O.V., Antuh E.A., Elizarova A.L. i Matveeva I.I., Sel'chuk V.YU., CHerkasov V.A. Prakticheskie rekomendacii po profilaktike i lecheniyu tromboembolicheskih oslozhnenij u onkologicheskih bol'nyh // Zlokachestvennye opuholi. Prakticheskie rekomendacii Rossijskogo obshchestva klinicheskoj onkologii. 2018. T. 8. № 3. Cpecvypusk 2. S. 604–609.
- Kakkar A.K., Williamson R.C.N. Prevention of venous thromboembolism in cancer patients // Semin. Thromb. Haemost. 1999. V. 25. № 2. P. 239–243.
- Ornstein D.L., Zacharski L.R. The use of heparin for treating human malignancies // Haemostasis. 1999. V. 29. Suppl 1. P. 48–60.
- Zacharski L.R., Prandoni P., Monreal M. Warfarin versus low-molecular-weight heparin therapy in cancer patients // Oncologist. 2005. V. 10. № 1. P. 72–79.
- Mousa S.A. Low-molecular-weight heparins in thrombosis and cancer: emerging links // Cardiovasc. Drug Rev. 2004a. V. 22. № 2. P. 121–134.
- Mousa S.A. Low-molecular-weight heparins in thrombosis and cancer // Semin. Thromb. Haemostas. 2004b. V. 30. Suppl. 1. P. 25–30.
- Kakkar A.K., Kadziola Z., Williamson R.C.N., Levine M.N., Low V., Lemoine N.R. Low molecular weight heparin (LMWH) therapy and survival in advanced cancer. In: (Proceedings) 44th Annual Meeting of the American-Society-of-Hematology (abstract) // Blood. 2002. V. 100. P. 148A.
- Tsimafeyeu I.V., Demidov L.V., Madzhuga A.V., Somonova O.V., Elizarova A.L. Hypercoagulability as a prognostic factor for survival in patients with metastatic renal cell carcinoma // J. Exp. Clin. Cancer Res. 2009. V. 28. № 30. P. 37–44.