title: Timed non-transferrin bound iron determinations probe the origin of chelatable iron pools during deferiprone regimens and predict chelation response.
abstract: BACKGROUND
  Plasma non-transferrin bound iron refers to heterogeneous plasma iron species, not bound to transferrin, which appear in conditions of iron overload and ineffective erythropoiesis. The clinical utility of non-transferrin bound iron in predicting complications from iron overload, or response to chelation therapy remains unproven. We undertook carefully timed measurements of non-transferrin bound iron to explore the origin of chelatable iron and to predict clinical response to deferiprone.
  
  
  METHODS
  Non-transferrin bound iron levels were determined at baseline and after 1 week of chelation in 32 patients with thalassemia major receiving deferiprone alone, desferrioxamine alone, or a combination of the two chelators. Samples were taken at baseline, following a 2-week washout without chelation, and after 1 week of chelation, this last sample being taken 10 hours after the previous evening dose of deferiprone and, in those receiving desferrioxamine, 24 hours after cessation of the overnight subcutaneous infusion. Absolute or relative non-transferrin bound iron levels were related to transfusional iron loading rates, liver iron concentration, 24-hour urine iron and response to chelation therapy over the subsequent year.
  
  
  RESULTS
  Changes in non-transferrin bound iron at week 1 were correlated positively with baseline liver iron, and inversely with transfusional iron loading rates, with deferiprone-containing regimens but not with desferrioxamine monotherapy. Changes in week 1 non-transferrin bound iron were also directly proportional to the plasma concentration of deferiprone-iron complexes and correlated significantly with urine iron excretion and with changes in liver iron concentration over the next 12 months.
  
  
  CONCLUSIONS
  The widely used assay chosen for this study detects both endogenous non-transferrin bound iron and the iron complexes of deferiprone. The week 1 increments reflect chelatable iron derived both from liver stores and from red cell catabolism. These increments correlate with urinary iron excretion and the change in liver iron concentration over the subsequent year thus predicting response to deferiprone-containing chelation regimes. This clinical study was registered at clinical.trials.gov with the number NCT00350662.
authors.affiliation: Department of Pediatric Hematology, Ege University Faculty of Medicine, 35100 Bornova, Izmir, Turkey. yesim.aydinok@ege.edu.tr
authors.forename: Yesim
authors.initials: Y
authors.lastname: Aydinok
authors.forename: Patricia
authors.initials: P
authors.lastname: Evans
authors.forename: Chantal Y
authors.initials: CY
authors.lastname: Manz
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
mesh_terms: D000293:Adolescent; D001798:Blood Proteins / Q000378:metabolism; D001803:Blood Transfusion; D015913:Chelation Therapy; D002648:Child; D000077543:Deferiprone; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D006801:Humans; D007501:Iron / Q000097:blood / Q000652:urine; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019190:Iron Overload / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D008099:Liver / Q000378:metabolism; D008137:Longitudinal Studies; D011485:Protein Binding; D011728:Pyridones / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood / Q000188:drug therapy* / Q000652:urine
chemical_list: D001798:Blood Proteins; D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D007501:Iron; D003676:Deferoxamine