title: Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury.
abstract: Chronic blood transfusion is increasingly indicated in patients with sickle cell disease. Measuring resulting iron overload remains a challenge. Children without viral hepatitis enrolled in 2 trials for stroke prevention were examined for iron overload (STOP and STOP2; n = 271). Most received desferrioxamine chelation. Serum ferritin (SF) changes appeared nonlinear compared with prechelation estimated transfusion iron load (TIL) or with liver iron concentrations (LICs). Averaged correlation coefficient between SF and TIL (patients/observations, 26 of 164) was r = 0.70; between SF and LIC (patients/observations, 33 of 47) was r = 0.55. In mixed models, SF was associated with LIC (P = .006), alanine transaminase (P = .025), and weight (P = .026). Most patients with SF between 750 and 1500 ng/mL had a TIL between 25 and 100 mg/kg (72.8% +/- 5.9%; patients/observations, 24 of 50) or an LIC between 2.5 and 10 mg/g dry liver weight (75% +/- 0%; patients/observations, 8 of 9). Most patients with SF of 3000 ng/mL or greater had a TIL of 100 mg/kg or greater (95.3% +/- 6.7%; patients/observations, 7 of 16) or an LIC of 10 mg/g dry liver weight or greater (87.7% +/- 4.3%; patients/observations, 11 of 18). Although SF changes are nonlinear, levels less than 1500 ng/mL indicated mostly acceptable iron overload; levels of 3000 ng/mL or greater were specific for significant iron overload and were associated with liver injury. However, to determine accurately iron overload in patients with intermediately elevated SF levels, other methods are required. These trials are registered at www.clinicaltrials.gov as #NCT00000592 and #NCT00006182.
authors.affiliation: Morehouse School of Medicine, Atlanta, GA 30344, USA. tadamkiewicz@msm.edu
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Adamkiewicz
authors.forename: Miguel R
authors.initials: MR
authors.lastname: Abboud
authors.forename: Carole
authors.initials: C
authors.lastname: Paley
authors.forename: Nancy
authors.initials: N
authors.lastname: Olivieri
authors.forename: Melanie
authors.initials: M
authors.lastname: Kirby-Allen
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
authors.forename: James F
authors.initials: JF
authors.lastname: Casella
authors.forename: Ofelia A
authors.initials: OA
authors.lastname: Alvarez
authors.forename: Julio C
authors.initials: JC
authors.lastname: Barredo
authors.forename: Margaret T
authors.initials: MT
authors.lastname: Lee
authors.forename: Rathi V
authors.initials: RV
authors.lastname: Iyer
authors.forename: Abdullah
authors.initials: A
authors.lastname: Kutlar
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: McKie
authors.forename: Virgil
authors.initials: V
authors.lastname: McKie
authors.forename: Nadine
authors.initials: N
authors.lastname: Odo
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gee
authors.forename: Janet L
authors.initials: JL
authors.lastname: Kwiatkowski
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Woods
authors.forename: Thomas
authors.initials: T
authors.lastname: Coates
authors.forename: Winfred
authors.initials: W
authors.lastname: Wang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
mesh_terms: D000410:Alanine Transaminase; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications; D019540:Area Under Curve; D002648:Child; D003676:Deferoxamine / Q000627:therapeutic use; D005293:Ferritins / Q000097:blood*; D006801:Humans; D019190:Iron Overload / Q000209:etiology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology*; D012372:ROC Curve; D017262:Siderophores / Q000627:therapeutic use; D020521:Stroke / Q000517:prevention & control; D065227:Transfusion Reaction
chemical_list: D017262:Siderophores; D005293:Ferritins; D000410:Alanine Transaminase; D003676:Deferoxamine