title: Iron chelation by deferoxamine in sickle cell patients with severe transfusion-induced hemosiderosis: a randomized, double-blind study of the dose-response relationship.
abstract: Transfusion-induced hemosiderosis is a serious and potentially life-threatening complication for some patients with sickle cell anemia. The use of high-dose intravenous deferoxamine (DFO) has become widespread in spite of a paucity of published data on safety and efficacy. We report a randomized double-blind study of the dose-response relationship of intravenous DFO in six subjects with sickle cell anemia and severe transfusion-induced hemosiderosis (serum ferritin 4100 to 14,176 ng/ml). Each subject received three different doses of intravenous DFO for 3 days each while consuming a constant diet. Total iron excretion (urine and fecal) was 91% greater at 180 mg/kg/day DFO than at 60 mg/kg/day DFO, and fecal iron excretion became a relatively larger proportion of total excretion at higher doses. Subsequent treatment for 3 months with 150 mg/kg/day DFO caused a 33% to 60% reduction in serum ferritin and demonstrable improvement in hepatic function in all patients. No toxicity was encountered, but DFO at 180 mg/kg/day was associated with a significant increase in fecal zinc excretion when compared with that observed at lower doses.
authors.affiliation: Colorado Sickle Cell Treatment and Research Center, Denver.
authors.forename: C C
authors.initials: CC
authors.lastname: Silliman
authors.forename: V M
authors.initials: VM
authors.lastname: Peterson
authors.forename: D L
authors.initials: DL
authors.lastname: Mellman
authors.forename: D J
authors.initials: DJ
authors.lastname: Dixon
authors.forename: K M
authors.initials: KM
authors.lastname: Hambidge
authors.forename: P A
authors.initials: PA
authors.lastname: Lane
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000188:drug therapy; D003676:Deferoxamine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005243:Feces / Q000737:chemistry; D006486:Hemosiderosis / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007501:Iron / Q000378:metabolism / Q000652:urine; D007502:Iron Chelating Agents / Q000378:metabolism; D065227:Transfusion Reaction; D015032:Zinc / Q000652:urine
chemical_list: D007502:Iron Chelating Agents; D007501:Iron; D003676:Deferoxamine; D015032:Zinc