Thrombotic microangiopathy in cancer patients

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Thrombotic microangiopathy (TMA) is a rare phenomenon, which is severe pathology based on systemic microvascular thrombosis. TMA is characterized by thrombocytopenia and signs of microangiopathic hemolytic anemia. The review presents a modern data on the pathogenesis of tumor-associated thrombotic microangiopathy, considers the interaction of various effectors related to both tumor growth and metastasis process ― immune system activation, endotheliopathy formation, use of chemotherapeutic agents and targeted therapy in the pathogenesis of various forms of TMA. The interaction between the tumor tissue, hemostasis and immune systems are of the type of cascade of mutual activation, thus leading to the formation of a vicious circle, resulting in damage to endothelium and thrombosis in the microcirculatory channel, that is, the development of TMA. The formation of thromboembolism, which includes tumor tissue in the microvessels of the lungs, contributes to the development of pulmonary tumor thrombotic microangiopathy (PTTM). Сancer patients have higher vWF levels and lower ADAMTS13 levels or/and activity than the general population, often also depending on the stage of cancer: vWF and ADAMTS13 have been shown to be associated with thrombotic complications in cancer patients, and ADAMTS13 shows prognostic potential. Increased expression of complement proteins and/or activation of complement during chemotherapy, infectious and inflammatory complications may also cause TMA development. Pathogenesis of thrombotic microangiopathy also is associated with numerous chemotherapeutic agents, such as mitomycin C, gemcitabine, cisplatin, carboplatin and Bevacizumab, an inhibitor of VEGF. This may be the result of both the direct toxic effect of the drug on endothelium and damage of it by immune complexes caused by expression of the VEGF-antibodies. Usage of number of chemotherapeutic agents, especially anti-VEGF and tyrosine kinase inhibitors, which have a direct toxic effect on endothelium, are associated with the development of TMA. Mechanisms causing the development of TMA are considered as components of the hemostasis system, leading to the development of chronic, long-lasting disorders of the hemostasis system (chronic DIC syndrome) and are associated with high incidence of thrombotic complications.

Alexander D. Makatsariya

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
ORCID iD: 0000-0001-7415-4633
SPIN-code: 7538-2966

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD, PhD, Professor

Ismail Elalamy

I.M. Sechenov First Moscow State Medical University (Sechenov University); Sorbonna University

ORCID iD: 0000-0002-9576-1368

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992; 15-21 Rue de l'École de Médecine, 75006 Paris

Professor of the Department of  Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University; MD, PhD, Professor of Hospitaux Universitares Tenon, Medical University Sorbonne


Alexander V. Vorobev

I.M. Sechenov First Moscow State Medical University (Sechenov University)

ORCID iD: 0000-0002-4509-9281
SPIN-code: 5806-7062

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992


Angelina S. Bakhtina

I.M. Sechenov First Moscow State Medical University (Sechenov University)

ORCID iD: 0000-0002-6985-5635

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

Student of pediatric faculty

Muyang Meng

I.M. Sechenov First Moscow State Medical University (Sechenov University)

ORCID iD: 0000-0002-8326-556X

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

doctoral student of the Department of Obstetrics and Gynecology

Victoria O. Bitsadze

I.M. Sechenov First Moscow State Medical University (Sechenov University)

ORCID iD: 0000-0001-8404-1042
SPIN-code: 5930-0859

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD, PhD, Professor

Jamilya Kh. Khizroeva

I.M. Sechenov First Moscow State Medical University (Sechenov University)

ORCID iD: 0000-0002-0725-9686
SPIN-code: 8225-4976

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD, PhD, Professor

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Supplementary files

Supplementary Files Action
1. Fig. 1. Pathogenetic mechanisms of thrombotic thrombocytopenic purpura View (304KB) Indexing metadata
2. Fig. 2. Pathogenetic mechanisms of activation of the hemostatic system in conditions of tumor growth View (270KB) Indexing metadata


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