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