Severe iron deficiency was induced in rabbits by repeated phlebotomy and maintenance on an iron-deficient diet. Erythrocytes from these animals were studied at periods of 2-10 wk following the cessation of bloodletting and were found to have a shortened survival in vivo by the 51Cr technique. These cells were found to be more susceptible than normal cells to lysis during sterile 24-hr incubation in glucose-free balanced salt solution. The severely iron deficient erythrocyte also demonstrated an increased susceptibility to sulfhydryl inhibitors in vitro. Iron-deficient erythrocytes, despite their smaller volume, were found to have an impaired ability to filter through 5-µ Millipore filters. These studies suggest the following pathogenesis for the hemolysis seen in severe iron deficiency. The abnormal plasticity may lead to excessive trapping of these cells by the spleen and reticuloendothelial cells. Within this environment these metabolically abnormal cells are exposed to hostile conditions of stasis and glucose deprivation, which may then enhance their lysis.

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