title: The simultaneous occurrence of both hypercoagulability and hypofibrinolysis in blood and serum during systemic inflammation, and the roles of iron and fibrin(ogen).
abstract: Although the two phenomena are usually studied separately, we summarise a considerable body of literature to the effect that a great many diseases involve (or are accompanied by) both an increased tendency for blood to clot (hypercoagulability) and the resistance of the clots so formed (hypofibrinolysis) to the typical, 'healthy' or physiological lysis. We concentrate here on the terminal stages of fibrin formation from fibrinogen, as catalysed by thrombin. Hypercoagulability goes hand in hand with inflammation, and is strongly influenced by the fibrinogen concentration (and vice versa); this can be mediated via interleukin-6. Poorly liganded iron is a significant feature of inflammatory diseases, and hypofibrinolysis may change as a result of changes in the structure and morphology of the clot, which may be mimicked in vitro, and may be caused in vivo, by the presence of unliganded iron interacting with fibrin(ogen) during clot formation. Many of these phenomena are probably caused by electrostatic changes in the iron-fibrinogen system, though hydroxyl radical (OH˙) formation can also contribute under both acute and (more especially) chronic conditions. Many substances are known to affect the nature of fibrin polymerised from fibrinogen, such that this might be seen as a kind of bellwether for human or plasma health. Overall, our analysis demonstrates the commonalities underpinning a variety of pathologies as seen in both hypercoagulability and hypofibrinolysis, and offers opportunities for both diagnostics and therapies.
authors.affiliation: School of Chemistry and The Manchester Institute of Biotechnology, The University of Manchester, 131, Princess St, Manchester M1 7DN, Lancs, UK. dbk@manchester.ac.uk.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kell
authors.forename: Etheresia
authors.initials: E
authors.lastname: Pretorius
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000276:immunology*; D003198:Computer Simulation; D005337:Fibrin / Q000276:immunology*; D005340:Fibrinogen / Q000276:immunology*; D005342:Fibrinolysis / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D007501:Iron / Q000097:blood / Q000276:immunology*; D018448:Models, Immunological; D019851:Thrombophilia / Q000276:immunology*
chemical_list: D005337:Fibrin; D005340:Fibrinogen; D007501:Iron