title: Profound morphological changes in the erythrocytes and fibrin networks of patients with hemochromatosis or with hyperferritinemia, and their normalization by iron chelators and other agents.
abstract: It is well-known that individuals with increased iron levels are more prone to thrombotic diseases, mainly due to the presence of unliganded iron, and thereby the increased production of hydroxyl radicals. It is also known that erythrocytes (RBCs) may play an important role during thrombotic events. Therefore the purpose of the current study was to assess whether RBCs had an altered morphology in individuals with hereditary hemochromatosis (HH), as well as some who displayed hyperferritinemia (HF). Using scanning electron microscopy, we also assessed means by which the RBC and fibrin morphology might be normalized. An important objective was to test the hypothesis that the altered RBC morphology was due to the presence of excess unliganded iron by removing it through chelation. Very striking differences were observed, in that the erythrocytes from HH and HF individuals were distorted and had a much greater axial ratio compared to that accompanying the discoid appearance seen in the normal samples. The response to thrombin, and the appearance of a platelet-rich plasma smear, were also markedly different. These differences could largely be reversed by the iron chelator desferal and to some degree by the iron chelator clioquinol, or by the free radical trapping agents salicylate or selenite (that may themselves also be iron chelators). These findings are consistent with the view that the aberrant morphology of the HH and HF erythrocytes is caused, at least in part, by unliganded ('free') iron, whether derived directly via raised ferritin levels or otherwise, and that lowering it or affecting the consequences of its action may be of therapeutic benefit. The findings also bear on the question of the extent to which accepting blood donations from HH individuals may be desirable or otherwise.
authors.affiliation: Department of Physiology, University of Pretoria, Arcadia, South Africa.
authors.forename: Etheresia
authors.initials: E
authors.lastname: Pretorius
authors.affiliation: Department of Physiology, University of Pretoria, Arcadia, South Africa.
authors.forename: Janette
authors.initials: J
authors.lastname: Bester
authors.affiliation: Department of Physiology, University of Pretoria, Arcadia, South Africa.
authors.forename: Natasha
authors.initials: N
authors.lastname: Vermeulen
authors.affiliation: Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Lipinski
authors.affiliation: AMPATH National Reference Laboratory, Centurion, South Africa.
authors.forename: George S
authors.initials: GS
authors.lastname: Gericke
authors.affiliation: School of Chemistry and The Manchester Institute of Biotechnology, The University of Manchester, Lancs, United Kingdom.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kell
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D007464:Clioquinol / Q000627:therapeutic use; D003676:Deferoxamine / Q000627:therapeutic use; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005293:Ferritins / Q000037:antagonists & inhibitors / Q000097:blood*; D005337:Fibrin / Q000378:metabolism / Q000648:ultrastructure*; D006432:Hemochromatosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D053657:Platelet-Rich Plasma / Q000737:chemistry; D020156:Salicylic Acid / Q000627:therapeutic use; D020887:Selenious Acid / Q000627:therapeutic use; D013917:Thrombin / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D007502:Iron Chelating Agents; D017665:Hydroxyl Radical; D007464:Clioquinol; D005337:Fibrin; D005293:Ferritins; D007501:Iron; D013917:Thrombin; D020887:Selenious Acid; D003676:Deferoxamine; D020156:Salicylic Acid