Year: 2021
Type: article
Abstract: The blood coagulation cascade is essential for hemostasis but excessive activation can cause thrombosis. Importantly, recent studies have identified factors that contribute to thrombosis but not hemostasis. These include factor XII (FXII), tissue factor-positive microparticles (MPs) and neutrophil extracellular traps (NETs). Recent studies have shown that FXII plays a role in thrombosis but not hemostasis. FXII is activated in vivo by a variety of negatively-charged polyphosphates, which include extracellular RNA, DNA and inorganic polyphosphate (PolyP) that are released during cell damage and infection. These findings have triggered the development of nucleic acid-binding polymers as a new class of anticoagulant drug. Other studies have analyzed the role of MPs in experimental thrombosis. MPs are small membrane vesicles released from activated or apoptotic cells. We and others have found that tissue factor-positive MPs enhance thrombosis in mouse models and are elevated in the plasma of pancreatic cancer patients. Finally, NETs have been shown to contribute to experimental venous thrombosis in mouse models and are present in human thrombi. NETs are composed of chromatin fibers that are released from neutrophils undergoing cell death. NETs can capture platelets and increase fibrin deposition. The recent advances in our understanding of the factors contributing to thrombosis in animal models provide new opportunities for the development of safer anticoagulant drugs.
DOI: 10.17615/av72-sc06
Authors: Mackman, Nigel, Geddings, Julia E.
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4300155319