Chemotherapy and hemostasis disorders
https://doi.org/10.17749/2313-7347/ob.gyn.rep.2024.579
Abstract
Cancer patients are at risk of developing arterial and venous thrombosis during chemotherapy (CT) and after its cessation. A prothrombotic risk may arise via pathogenetic pathways such as activation of external and internal coagulation pathways, decreased anticoagulant levels, platelet activation, fibrinolysis blockade, etc. Chemotherapeutic agents exert direct cytotoxicity, as well as indirectly suppress cellular processes necessary for tumor cell proliferation. CT-related cytotoxicity act on both tumor and healthy body cells. Available targeted drugs with improved selectivity for tumor cells are also associated with thrombosis risk. Low molecular weight heparins, which effectively reduce the risk of venous thromboembolism, have not yet been officially recommended for routine use during CT. Here, we discuss the prothrombotic effects of various antitumor agents aimed at gaining deeper understanding of the underlying mechanisms that may allow to develop new strategies for prevention and treatment of such formidable complications.
About the Authors
E. V. SlukhanchukRussian Federation
Ekaterina V. Slukhanchuk, MD, PhD
8 bldg. 2, Trubetskaya Str., Moscow 119991
V. O. Bitsadze
Russian Federation
Victoria O. Bitsadze, MD, Dr Sci Med, Prof., Professor of RAS
Scopus Author ID: 6506003478. WoS ResearcherID: F-8409-2017
8 bldg. 2, Trubetskaya Str., Moscow 119991
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 119991
J. Kh. Khizroeva
Russian Federation
Jamilya Kh. Khizroeva, MD, Dr Sci Med, Prof.
Scopus Author ID: 57194547147. WoS ResearcherID: F-8384-2017
8 bldg. 2, Trubetskaya Str., Moscow 119991
K. N. Grigoreva
Russian Federation
Kristina N. Grigoreva, MD.
8 bldg. 2, Trubetskaya Str., Moscow 119991
N. R. Gashimova
Russian Federation
Nilufar R. Gashimova, MD.
8 bldg. 2, Trubetskaya Str., Moscow 119991
N. A. Makatsariya
Russian Federation
Nataliya A. Makatsariya, MD, PhD.
WoS ResearcherID: F-8406-2017
8 bldg. 2, Trubetskaya Str., Moscow 119991
D. V. Blinov
Russian Federation
Dmitry V. Blinov, MD, PhD, MBA
Scopus Author ID: 6701744871. WoS ResearcherID: E-8906-2017
4—10 Sadovaya-Triumfalnaya Str., Moscow 127006
5 bldg. 1-1a, 2-ya Brestskaya Str., Moscow 123056
6 bldg. 1, Rodnikovaya Str., Village Goluboe, Moscow region 141551
V. N. Galkin
Russian Federation
Vsevolod N. Galkin - MD, Dr Sci Med, Prof.
4 Kolomenskiy Proezd, Moscow 115446
A. Yu. Shatilina
Russian Federation
Anastasia Yu. Shatilina
8 bldg. 2, Trubetskaya Str., Moscow 119991
E. M. Lyadnova
Russian Federation
Elizaveta M. Lyadnova
8 bldg. 2, Trubetskaya Str., Moscow 119991
N. A. Shulga
Russian Federation
Natalia A. Shulga
12, Leninskie Gory, Moscow 119234
L. T. Toguzaeva
Russian Federation
Leylya T. Toguzaeva, MD.
4 Academika Oparina Str., Moscow 117997
S. Morkos
United Arab Emirates
Simon Morkos, Dr Sci Med, Prof.
Al Barsha, Khadaek Mohammed Bin Rashid, Dubai
J.-C. Gris
Russian Federation
Jean-Christophe Gris, MD, Dr Sci Med, Prof.
Scopus Author ID: 7005114260. WoS ResearcherID: AAA-2923-2019
8 bldg. 2, Trubetskaya Str., Moscow 119991
163 Rue Auguste Broussonnet, Montpellier 34090, France
I. Elalamy
Russian Federation
Ismail Elalamy, MD, Dr Sci Med, Prof.
Scopus Author ID: 7003652413. WoS ResearcherID: AAC-9695-2019
8 bldg. 2, Trubetskaya Str., Moscow 119991
12 Rue de l’Ecole de Medecine, Paris 75006, France
4 Rue de la Chine, Paris 75020, France
G. Gerotziafas
Russian Federation
Grigories Gerotziafas, MD, Dr Sci Med, Prof.
8 bldg. 2, Trubetskaya Str., Moscow 119991
12 Rue de l’Ecole de Medecine, Paris 75006, France
4 Rue de la Chine, Paris 75020, France
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 119991
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What is already known about this subject?
► Chemotherapy (СТ) increases a risk of deep vein thrombosis (DVT) and recurrent DVT by 6- and 2-fold, respectively. Recent studies have proven the role of antitumor СТ in elevating the thrombotic risk in cancer patients.
► Analysis of thrombosis pathogenesis during СТ is complicated by applying various drug combinations and treatment regimens, as well as the inability to fully assess a baseline patient hemostasis state, including the presence of acquired and congenital thrombophilia, etc.
► Despite whole set of data showing that systemic СТ promotes development of venous and arterial thrombosis in cancer patients, no consensus regarding underlying pathogenetic mechanisms has been achieved.
What are the new findings?
► This article analyzes the mechanisms of prothrombogenic action of major currently used СТ drugs. All variants of pathogenetic pathways for enabling such effects are described in detail thereby allowing to model various strategies that counteract thrombosis.
How might it impact on clinical practice in the foreseeable future?
► The prothrombogenic effect of chemotherapy drugs necessitates to consider the issue of simultaneous planning of antithrombotic prophylaxis. A better understanding of the mechanisms that control СТ-associated thrombosis will enable the development of optimal anticoagulant regimens that minimize thrombotic and bleeding risks.
► It is obviously required to develop and implement a prognostic model for thrombosis risk stratification in patients undergoing СТ followed by assessing a need for conducting prophylactic anticoagulation as well as randomized controlled trials on using prophylactic anticoagulation during СТ.
Review
For citations:
Slukhanchuk E.V., Bitsadze V.O., Solopova A.G., Khizroeva J.Kh., Grigoreva K.N., Gashimova N.R., Makatsariya N.A., Blinov D.V., Galkin V.N., Shatilina A.Yu., Lyadnova E.M., Shulga N.A., Toguzaeva L.T., Morkos S., Gris J., Elalamy I., Gerotziafas G., Makatsariya A.D. Chemotherapy and hemostasis disorders. Obstetrics, Gynecology and Reproduction. 2024;18(6):835-846. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2024.579

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