title: Measurement of microparticle tissue factor activity in clinical samples: A summary of two tissue factor-dependent FXa generation assays.
abstract: Thrombosis is a leading cause of morbidity and mortality. Detection of a prothrombotic state using biomarkers would be of great benefit to identify patients at risk of thrombosis that would benefit from thromboprophylaxis. Tissue factor (TF) is a highly procoagulant protein that under normal conditions is not present in the blood. However, increased levels of TF in the blood in the form of microparticles (MPs) (also called extracellular vesicles) are observed under various pathological conditions. In this review, we will discuss studies that have measured MP-TF activity in a variety of diseases using two similar FXa generation assay. One of the most robust signals for MP-TF activity (16-26 fold higher than healthy controls) is observed in pancreatic cancer patients with venous thromboembolism. In this case, the TF+ MPs appear to be derived from the cancer cells. Surprisingly, cirrhosis and acute liver injury are associated with 17-fold and 38-fold increases in MP-TF activity, respectively. Based on mouse models, we speculate that the TF+ MPs are derived from hepatocytes. More modest increases are observed in patients with urinary tract infections (6-fold) and in a human endotoxemia model (9-fold) where monocytes are the likely source of the TF+ MPs. Finally, there is no increase in MP-TF activity in the majority of cardiovascular disease patients. These studies indicate that MP-TF activity may be a useful biomarker to identify patients with particular diseases that have an increased risk of thrombosis.
authors.affiliation: McAllister Heart Institute, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Hisada
authors.affiliation: McAllister Heart Institute, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Wyeth
authors.initials: W
authors.lastname: Alexander
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Raj
authors.initials: R
authors.lastname: Kasthuri
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Voorhees
authors.affiliation: Karolinska Institute, Department of Medicine Solna, Unit of Rheumatology, Stockholm, Sweden.
authors.forename: Fariborz
authors.initials: F
authors.lastname: Mobarrez
authors.affiliation: Cardiovascular Research Center, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Taylor
authors.affiliation: Cardiovascular Research Center, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Coleen
authors.initials: C
authors.lastname: McNamara
authors.affiliation: Karolinska Institute, Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
authors.forename: Hakan
authors.initials: H
authors.lastname: Wallen
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Witkowski
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Key
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauch
authors.affiliation: McAllister Heart Institute, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: nigel_mackman@med.unc.edu.
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000378:metabolism; D001780:Blood Coagulation Tests / Q000379:methods; D055252:Cell-Derived Microparticles / Q000378:metabolism / Q000473:pathology*; D015951:Factor Xa / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000473:pathology; D013925:Thromboplastin / Q000032:analysis / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D013925:Thromboplastin; D015951:Factor Xa
keywords: Cancer; Microparticles; Thrombosis, tissue factor