title: Differences in morphology of fibrin clots induced with thrombin and ferric ions and its pathophysiological consequences.
abstract: The activation of blood coagulation leads to the formation of thrombin that, in turn, converts soluble plasma fibrinogen into insoluble fibrin clot. In healthy individuals, fibrin is effectively degraded; however, in prothrombotic states, proteolysis of fibrin clots are often delayed or even inhibited, and is associated with altered fibrin structure. We have previously shown that in inflammatory conditions like stroke and diabetes, this fibrin forms dense matted deposits. Although there are several factors that modify fibrin structure and delay fibrinolysis in these conditions, no mechanism is yet known to be responsible for a persistent presence of thrombi in the coronary and/or cerebral circulations. It seems, therefore, desirable to better understand this phenomenon in order to improve the effectiveness of thrombolytic therapies. Here, we show that ferric ions can activate non-enzymatic blood coagulation resulting in the formation of fibrin-like dense matted deposits (DMD) demonstrable by electron scanning microscopy (SEM). These DMDs are similar to those found in stroke and diabetes. On the basis of these findings we can conclude that the spontaneous formation of fibrin-like dense deposits in patients' blood may be a consequence of what is known as iron overload. Therefore, it is possible that inactivation of unbound iron in blood by small molecular weight chelating agents may prevent thrombotic consequences of the excessive accumulation of iron in the circulation.
authors.affiliation: Department of Physiology, Faculty of Health Sciences, University of Pretoria, Arcadia, South Africa. resia.pretorius@up.ac.za
authors.forename: E
authors.initials: E
authors.lastname: Pretorius
authors.forename: B
authors.initials: B
authors.lastname: Lipinski
mesh_terms: D001777:Blood Coagulation; D003920:Diabetes Mellitus / Q000097:blood; D005260:Female; D005290:Ferric Compounds / Q000097:blood / Q000737:chemistry*; D005337:Fibrin / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use; D019190:Iron Overload / Q000097:blood / Q000150:complications / Q000188:drug therapy; D008297:Male; D020521:Stroke / Q000097:blood; D013917:Thrombin / Q000737:chemistry* / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control
chemical_list: D005290:Ferric Compounds; D007502:Iron Chelating Agents; D005337:Fibrin; D013917:Thrombin