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Neutrophil extracellular traps: a role in inflammation and dysregulated hemostasis as well as in patients with COVID-19 and severe obstetric pathology

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Numerous studies have proven a close relationship between inflammatory diseases and the state of hypercoagulability. In fact, thromboembolic complications represent one of the main causes of disability and mortality in acute and chronic inflammatory diseases, cancer and obstetric complications. Despite this, the processes of hemostasis and immune responses have long been considered separately; currently, work is underway to identify the molecular basis for a relationship between such systems. It has been identified that various pro-inflammatory stimuli are capable of triggering a coagulation cascade, which in turn modulates inflammatory responses. Neutrophil extracellular traps (NETs) are the networks of histones of extracellular DNA generated by neutrophils in response to inflammatory stimuli. The hemostasis is activated against infection in order to minimize the spread of infection and, if possible, inactivate the infectious agent. Another molecular network is based on fibrin. Over the last 10 years, there has been accumulated a whole body of evidence that NETs and fibrin are able to form a united network within a thrombus, stabilizing each other. Similarities and molecular cross-reactions are also present in the processes of fibrinolysis and lysis of NETs. Both NETs and von Willebrand factor (vWF) are involved in thrombosis as well as inflammation. During the development of these conditions, a series of events occurs in the microvascular network, including endothelial activation, NETs formation, vWF secretion, adhesion, aggregation, and activation of blood cells. The activity of vWF multimers is regulated by the specific metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Studies have shown that interactions between NETs and vWF can lead to arterial and venous thrombosis and inflammation. In addition, the contents released from activated neutrophils or NETs result in decreased ADAMTS-13 activity, which can occur in both thrombotic microangiopathies and acute ischemic stroke. Recently, NETs have been envisioned as a cause of endothelial damage and immunothrombosis in COVID-19. In addition, vWF and ADAMTS-13 levels predict COVID-19 mortality. In this review, we summarize the biological characteristics and interactions of NETs, vWF, and ADAMTS-13, the effect of NETs on hemostasis regulation and discuss their role in thrombotic conditions, sepsis, COVID-19, and obstetric complications.

About the Authors

A. D. Makatsariya
Sechenov University
Russian Federation

Alexander D. Makatsariya - MD, Dr Sci Med, Academician of RAS, Professor, Head of the Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991.

Scopus Author ID: 57222220144.

Researcher ID: M-5660-2016.

E. V. Slukhanchuk
Sechenov University; Petrovsky National Research Centre of Surgery
Russian Federation

Ekaterina V. Slukhanchuk - MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University, Moscow Russia; Obstetrician-Gynecologist, Department of Abdominal Surgery and Oncology 2, Petrovsky National Research Centre of Surgery.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991; 2 Abrikosovskiy Lane, Moscow 119991.

V. O. Bitsadze
Sechenov University
Russian Federation

Victoria O. Bitsadze - MD, Dr Sci Med, Professor of RAS, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991.

Scopus Author ID: 6506003478.

Researcher ID: F-8409-2017.

J. Kh. Khizroeva
Sechenov University
Russian Federation

Jamilya Kh. Khizroeva - MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991.

Scopus Author ID: 57194547147.

Researcher ID: F-8384-2017.

M. V. Tretyakova
«Medical Center» LLC
Russian Federation

Maria V. Tretyakova - MD, PhD, Obstetrician-Gynecologist, Department of Gynecology, «Medical Center» LLC.

15/1 Timura Frunze Str., Moscow 119021.

N. A. Makatsariya
Sechenov University
Russian Federation

Nataliya A. Makatsariya - MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991.

Researcher ID: F-8406-2017.

S. V. Akinshina
«Medical Centre for Women» LLC
Russian Federation

Svetlana V. Akinshina - MD, PhD, Obstetrician-Gynecologist, Hematologist, «Medical Centre for Women» LLC.

62 Str. Zemlyanoi Val, Moscow 109004.

A. S. Shkoda
Vorokhobov City Clinical Hospital № 67, Moscow Healthcare Department
Russian Federation

Andrey S. Shkoda - MD, Dr Sci Med, Professor, Chief Physician, Vorokhobov City Clinical Hospital № 67.

2/44 Salyama Adilya Str., Moscow 123423.

L. L. Pankratyeva
Vorokhobov City Clinical Hospital № 67, Moscow Healthcare Department; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Health Ministry of Russian Federation
Russian Federation

Liudmila L. Pankratyeva - MD, Dr Sci Med, Head of the Clinical Research Center, Vorokhobov City Clinical Hospital № 67; Neonatologist, Hematologist, Associate Professor, Professor of the Department of Pediatrics and Health Organization, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.

2/44 Salyama Adilya Str., Moscow 123423; 1 Samora Machel Str., Moscow 117997.

Scopus Author ID: 7006391091.

Author ID: 697284.

G. C. Di Renzo
Sechenov University; Center for Prenatal and Reproductive Medicine, University of Perugia
Russian Federation

Gian C. Di Renzo - MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University; Director of the Center for Prenatal and Reproductive Medicine, University of Perugia, Italy; Honorary Secretary General of the International Federation of Gynecology and Obstetrics (FIGO).

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991; Umbria, Perugia, Piazza Italia.

Scopus Author ID: 7103191096.

Researcher ID: P-3819-2017.

G. Rizzo
Sechenov University; University of Rome Tor Vergata
Russian Federation

Giuseppe Rizzo - MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University; Professor, Director, Division of Maternal and Fetal Medicine, Ospedale Cristo Re, University of Rome Tor Vergata.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991; Rome.

Scopus Author ID: 7102724281.

Researcher ID: G-8234-2018.

K. N. Grigorieva
Sechenov University
Russian Federation

Kristina N. Grigoreva - MD, Medical Resident, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991.

V. I. Tsibizova
Almazov National Medical Research Centre, Health Ministry of Russian Federation
Russian Federation

Valentina I. Tsibizova - MD, PhD, Obstetrician-Gynecologist, Research Laboratory of Operative Gynecology, Institute of Perinatology and Pediatrics; Physician, Department of Functional and Ultrasound Diagnostics, Almazov National Medical Research Centre.

2 Akkuratova Str., Saint Petersburg 197341.

J.-C. Gris
Sechenov University; University of Montpellier
Russian Federation

Jean-Christophe Gris - MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University,; University of Montpellier.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991; 163 Rue Auguste Broussonnet, Montpellier 34090.

Researcher ID: AAA-2923-2019.

I. Elalamy
Sechenov University; Medicine Sorbonne University; Hospital Tenon
Russian Federation

Ismail Elalamy - MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health, Sechenov University; Professor, Medicine Sorbonne University, Paris, France; Director of Hematology, Department of Thrombosis Center, Hospital Tenon.

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991; 12 Rue de l’École de Médecine, 75006 Paris; 4 Rue de la Chine, 75020 Paris.

Scopus Author ID: 7003652413.

Researcher ID: AAC-9695-2019.


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For citations:

Makatsariya A.D., Slukhanchuk E.V., Bitsadze V.O., Khizroeva J.K., Tretyakova M.V., Makatsariya N.A., Akinshina S.V., Shkoda A.S., Pankratyeva L.L., Di Renzo G.C., Rizzo G., Grigorieva K.N., Tsibizova V.I., Gris J., Elalamy I. Neutrophil extracellular traps: a role in inflammation and dysregulated hemostasis as well as in patients with COVID-19 and severe obstetric pathology. Obstetrics, Gynecology and Reproduction. 2021;15(4):335-350.

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