title: New players in haemostasis and thrombosis.
abstract: The blood coagulation cascade is essential for haemostasis, but excessive activation can cause thrombosis. Importantly, recent studies have identified factors that contribute to thrombosis but not haemostasis. These include factor XII (FXII), tissue factor-positive microparticles (MPs) and neutrophil extracellular traps (NETs). Studies have shown that FXII plays a role in thrombosis but not haemostasis. 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 led to the development of nucleic acid-binding polymers as a new class of anticoagulant drug. Other studies have analysed 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.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Geddings
authors.affiliation: Nigel Mackman, PhD, Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA, Tel.: +1 919 843 3961, Fax: +1 919 966 7639, E-mail: nmackman@med.unc.edu.
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D017209:Apoptosis; D001777:Blood Coagulation; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D055808:Drug Discovery; D005174:Factor XII / Q000378:metabolism; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D051379:Mice; D023421:Models, Animal; D009504:Neutrophils / Q000502:physiology*; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood* / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D005174:Factor XII; D013925:Thromboplastin
keywords: Coagulation factors; arterial thrombosis; deep-vein thrombosis; microparticles; thrombosis