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.
