title: Iron-enhanced coagulation is attenuated by chelation: thrombelastographic and ultrastructural analysis.
abstract: Increased circulating ferritin and free iron have been found in a variety of disease states associated with thrombophilia. When blood or plasma is exposed to iron addition, characteristic changes in thrombus formation are observed by scanning electron microscopy, which include fusion of fibrin polymers, matting, and even sheeting of fibrin. A primary mechanism posited to explain iron-mediated hypercoagulability is hydroxyl radical formation and modification of fibrinogen; however, iron has also been demonstrated to bind to fibrinogen. We have recently demonstrated that iron enhances coagulation, manifested as a decrease in the time of onset of coagulation. Using clinically encountered concentrations of iron created by addition of FeCl3 to human plasma, we demonstrated that iron-mediated changes in reaction time determined by thrombelastography or changes in thrombus ultrastructure were significantly, but not completely, reversed by iron chelation with deferoxamine. Thus, reversible iron binding to fibrinogen mechanistically explains a significant portion of coagulation kinetic and ultrastructural hypercoagulability. Further investigation is needed to determine whether residual iron binding or other iron-mediated effects is responsible for hypercoagulability observed after chelation.
authors.affiliation: aDepartment of Anesthesiology, The University of Arizona College of Medicine, Tucson, Arizona, USA bDepartment of Physiology, Faculty of Health Sciences, University of Pretoria, Arcadia, South Africa.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
authors.forename: Etheresia
authors.initials: E
authors.lastname: Pretorius
mesh_terms: D001777:Blood Coagulation; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000737:chemistry*; D003676:Deferoxamine / Q000737:chemistry*; D005290:Ferric Compounds / Q000037:antagonists & inhibitors / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D007502:Iron Chelating Agents / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D053657:Platelet-Rich Plasma / Q000737:chemistry*; D013916:Thrombelastography; D010959:Tissue Plasminogen Activator / Q000737:chemistry
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator; D003676:Deferoxamine; C024555:ferric chloride