An extracorporeal hollow-fiber device with immobilized
desferrioxamine (DFO) was developed for the removal of nontransferrin-bound
iron (NTBI) from blood, without the toxicity of parenteral chelation. When blood circulates through the fibers having pores with 30 kD cut-off, non-
transferrin-bound-
iron (NTBI) crosses the fiber pores and is chelated by the immobilized
desferrioxamine. Removal of circulating
iron stimulates
iron release from larger
proteins and tissue stores, establishing continuous
iron flow to the immobilized
chelator. During in vitro circulation through a device,
iron removed from blood of
hemodialysis or sickle cell patients was proportional to, but always in less than 50% of the initial
iron level. We attribute the inability to remove more serum
iron to irreversible
iron binding by
transferrin. To investigate where removable and fixed
iron was bound,
iron binding proteins were analyzed in sera from six patients with genetic
anemias and
iron overload. Sera separated by sieving chromatography contained 1-14% of the
iron in the < 30 kD
protein pool, 26-48% was in the combined non-
transferrin pools. Sera from
hemochromatosis patients without
iron overload did not contain NTBI. Circulation of
hemochromatosis blood through the device removed one third of the
iron, this came from all molecular weight fractions.
Iron removal by the device from the < 30 kD pool appears to establish a disequilibrium, that stimulates continuous
iron release from
ligands with low
iron affinity, renewing the pool in the < 30 kD range, which includes potentially toxic NTBI.
Therapy with the
chelator device having immobilized
desferrioxamine should be beneficial for treatment of patients with
iron overload.