Deferiprone therapy in homozygous human beta-thalassemia removes erythrocyte membrane free iron and reduces KCl cotransport activity

Deposition of free iron is a characteristic feature of beta-thalassemia (be ta-thal) red blood cells believed to play an important role in the generati on of oxidative Injury to the cell membrane. Increased red blood cell KCI c otransport, reduced K content, and cell dehydration are also found in beta- thal red blood cells. It is not known, however, whether deposition of free iron plays a role in these membrane transport changes. To explore this issu e, we studied-both in vitro and in vivo-the effect on KCI cotransport of re moving red blood cell membrane tree iron from beta-thal erythrocytes, Eleve n patients with beta-thal major who underwent long-term transfusion and wer e treated with deferiprone (75 mg/kg/day) for 9 months participated in the study. Deferiprone therapy removed membrane free iron from beta-thal erythr ocytes, which was followed by reduced KCI cotransport activity The reduced KCI cotransport activity was accompanied by an increase in the red blood ce ll K content. These data suggest that the increased activity of KCI cotrans port in beta-thal red blood cells is mediated by the deposition of membrane free iron, a mechanism that may be attenuated by deferiprone therapy.