TY - JOUR
T1 - Iron-enhanced coagulation is attenuated by chelation
T2 - A thrombelastographic and ultrastructural analysis
AU - Nielsen, Vance G.
AU - Pretorius, Etheresia
N1 - Publisher Copyright:
© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Coagulation
KW - Electron microscopy
KW - Iron
KW - Thrombelastography
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U2 - 10.1097/MBC.0000000000000160
DO - 10.1097/MBC.0000000000000160
M3 - Article
C2 - 24991945
AN - SCOPUS:84919735043
SN - 0957-5235
VL - 25
SP - 845
EP - 850
JO - Blood Coagulation and Fibrinolysis
JF - Blood Coagulation and Fibrinolysis
IS - 8
ER -