title: Interaction of fibrin with red blood cells: the role of iron.
abstract: Activation of coagulation pathways results in the formation of hemostatic fibrin plugs. Under normal physiologic conditions fibrin clots are gradually, albeit completely, degraded by a fibrinolytic enzyme system to ensure proper wound healing and/or blood vessel patency. Yet in pathological situations, thrombi are not effectively removed, leading to chronic thrombosis. The susceptibility of blood clots to enzymatic degradation depends on the structure and properties of fibrin fibers. Many factors have been suspected as culprits, including red blood cells (RBCs) that become transiently trapped within fibrin mesh. Here, the authors show that there is indeed a specific interaction between RBCs and fibrin-like fibers identified here as dense matted deposits (DMDs) by means of scanning electron microscopy (SEM). It is emphasized that such interactions can be observed in ischemic stroke patients, but not from healthy subjects. However, DMD/RBC aggregates can be induced in normal blood by the additions of trivalent iron ions. The plausible mechanism of the enhanced fibrin-red blood cell interaction is based on the previously described iron-induced generation of hydroxyl radicals. These radicals cause, in turn, non-enzymatic formation of fibrinogen aggregates remarkably resistant to fibrinolysis that are also similar to DMDs described in this paper. In conclusion, this relatively simple SEM analysis may become a convenient tool for diagnosing prothrombotic conditions associated with iron overload. It is suggested that future research on prevention and treatment of ischemic stroke and other thrombosis associated diseases should include testing of iron-chelating and hydroxyl radical-scavenging agents.
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Lipinski
authors.forename: Etheresia
authors.initials: E
authors.lastname: Pretorius
authors.forename: Hester M
authors.initials: HM
authors.lastname: Oberholzer
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: van der Spuy
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D005290:Ferric Compounds / Q000494:pharmacology; D005337:Fibrin / Q000378:metabolism / Q000648:ultrastructure*; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D005337:Fibrin; D005340:Fibrinogen; D007501:Iron; C024555:ferric chloride