Inhibitors of Polyphosphate and Neutrophil Extracellular Traps

Sreeparna Vappala; Stephanie A. Smith; Jayachandran N. Kizhakkedathu; James H. Morrissey

doi:10.1055/s-0043-1768936

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2024; 50(07): 970-977
DOI: 10.1055/s-0043-1768936

Review Article

Inhibitors of Polyphosphate and Neutrophil Extracellular Traps

Sreeparna Vappala

¹Department of Pathology and Laboratory Medicine, Centre for Blood Research, Life Science Institute, University of British Columbia, Vancouver, British Columbia, Canada

,

Stephanie A. Smith

²Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan

,

Jayachandran N. Kizhakkedathu

¹Department of Pathology and Laboratory Medicine, Centre for Blood Research, Life Science Institute, University of British Columbia, Vancouver, British Columbia, Canada

³Department of Chemistry, School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada

,

James H. Morrissey

²Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan

› Author Affiliations

Abstract

The contact pathway of blood clotting has received intense interest in recent years as studies have linked it to thrombosis, inflammation, and innate immunity. Because the contact pathway plays little to no role in normal hemostasis, it has emerged as a potential target for safer thromboprotection, relative to currently approved antithrombotic drugs which all target the final common pathway of blood clotting. Research since the mid-2000s has identified polyphosphate, DNA, and RNA as important triggers of the contact pathway with roles in thrombosis, although these molecules also modulate blood clotting and inflammation via mechanisms other than the contact pathway of the clotting cascade. The most significant source of extracellular DNA in many disease settings is in the form of neutrophil extracellular traps (NETs), which have been shown to contribute to incidence and severity of thrombosis. This review summarizes known roles of extracellular polyphosphate and nucleic acids in thrombosis, with an emphasis on novel agents under current development that target the prothrombotic activities of polyphosphate and NETs.

Keywords

DNA - RNA - neutrophil extracellular traps - polyphosphate - thrombosis

Full Text

References

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