Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Oct 12;20(1):63.
doi: 10.1186/s12959-022-00421-y.

Clinical significance of neutrophil extracellular traps biomarkers in thrombosis

Xiangbo Xu #  1   2   3 , Yuting Wu #  2   3 , Shixue Xu #  1 , Yue Yin  1 , Walter Ageno  4 , Valerio De Stefano  5 , Qingchun Zhao  6   7 , Xingshun Qi  8   9
Affiliations
Review

Clinical significance of neutrophil extracellular traps biomarkers in thrombosis

Xiangbo Xu et al. Thromb J. .

Abstract

Neutrophil extracellular traps (NETs) may be associated with the development of thrombosis. Experimental studies have confirmed the presence of NETs in thrombi specimens and potential role of NETs in the mechanisms of thrombosis. Clinical studies also have demonstrated significant changes in the levels of serum or plasma NETs biomarkers, such as citrullinated histones, myeloperoxidase, neutrophil elastase, nucleosomes, DNA, and their complexes in patients with thrombosis. This paper aims to comprehensively review the currently available evidence regarding the change in the levels of NETs biomarkers in patients with thrombosis, summarize the role of NETs and its biomarkers in the development and prognostic assessment of venous thromboembolism, coronary artery diseases, ischemic stroke, cancer-associated thromboembolism, and coronavirus disease 2019-associated thromboembolism, explore the potential therapeutic implications of NETs, and further discuss the shortcomings of existing NETs biomarkers in serum and plasma and their detection methods.

Keywords: Citrullinated histones; Myeloperoxidase; Neutrophil; Neutrophil extracellular traps; Thrombosis.

PubMed Disclaimer

Conflict of interest statement

No competing interests.

Figures

Fig. 1
Fig. 1
NETs formation and thrombosis Abbreviations: H3Cit, Citrullinated histone H3; MPO, Myeloperoxidase; NADPH, Nicotinamide adenine dinucleotide phosphate; NE, Neutrophil elastase; NETs, Neutrophil extracellular traps; PAD4, Peptidyl arginine deiminase 4; ROS, Reactive oxygen species
Fig. 2
Fig. 2
A schematic diagram of NETs biomarkers detected in human VTE, CAD, MI, IS, cancer-associated thromboembolism, and COVID-2019-associated thromboembolism Notes: 1 NETs biomarkers that have been explored in human thrombi specimens. 2 NETs biomarkers that have been explored in human plasma/serum. √ NETs biomarkers that have been explored for diagnosis, prognostication, and/or treatment. × NETs biomarkers that have not been explored for diagnosis, prognostication, or treatment. Abbreviations: CAD, Coronary artery diseases; COVID, Coronavirus disease 2019; DVT, Deep vein thrombosis; H3Cit, Citrullinated histone H3; H4Cit, Citrullinated histone H4; IS, Ischemic stroke; MI, Myocardial infarction; MPO, Myeloperoxidase; NE, Neutrophil elastase; NETs, Neutrophil extracellular traps; PAD4, Peptidyl arginine deiminase 4; PE, Pulmonary embolism; PVT, Portal vein thrombosis
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Furie B, Furie BC. Mechanisms of thrombus formation [J] N Engl J Med. 2008;359(9):938–949. doi: 10.1056/NEJMra0801082. - DOI - PubMed
    1. Beckman MG, Hooper WC, Critchley SE, Ortel TL. Venous thromboembolism: a public health concern [J] Am J Prev Med. 2010;38(4 Suppl):S495–501. doi: 10.1016/j.amepre.2009.12.017. - DOI - PubMed
    1. Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, et al. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015 [J] J Am Coll Cardiol. 2017;70(1):1–25. doi: 10.1016/j.jacc.2017.04.052. - DOI - PMC - PubMed
    1. Lehman HK, Segal BH. The role of neutrophils in host defense and disease [J] J Allergy Clin Immunol. 2020;145(6):1535–1544. doi: 10.1016/j.jaci.2020.02.038. - DOI - PMC - PubMed
    1. Thålin C, Hisada Y, Lundström S, Mackman N, Wallén H. Neutrophil Extracellular Traps: Villains and Targets in Arterial, Venous, and Cancer-Associated Thrombosis [J] Arterioscler Thromb Vasc Biol. 2019;39(9):1724–1738. doi: 10.1161/atvbaha.119.312463. - DOI - PMC - PubMed