title: Organ iron accumulation in chronically transfused children with sickle cell anaemia: baseline results from the TWiTCH trial.
abstract: Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH) trial is a randomized, open-label comparison of hydroxycarbamide (also termed hydroxyurea) versus continued chronic transfusion therapy for primary stroke prevention in patients with sickle cell anaemia (SCA) and abnormal TCD. Severity and location of iron overload is an important secondary outcome measure. We report the baseline findings of abdominal organ iron burden in 121 participants. At enrollment, patients were young (9·8 ± 2·9 years), predominantly female (60:40), and previously treated with transfusions (4·1 ± 2·4 years) and iron chelation (3·1 ± 2·1 years). Liver iron concentration (LIC; 9·0 ± 6·6 mg/g dry weight) and serum ferritin were moderately elevated (2696 ± 1678 μg/l), but transferrin was incompletely saturated (47·2 ± 23·6%). Spleen R2* was 509 ± 399 Hz (splenic iron ~13·9 mg/g) and correlated with LIC (r(2)  = 0·14, P = 0·0008). Pancreas R2* was increased in 38·3% of patients but not to levels associated with endocrine toxicity. Kidney R2* was increased in 80·7% of patients; renal iron correlated with markers of intravascular haemolysis and was elevated in patients with increased urine albumin-creatinine ratios. Extra-hepatic iron deposition is common among children with SCA who receive chronic transfusions, and could potentiate oxidative stress caused by reperfusion injury and decellularized haemoglobin.
authors.affiliation: Department of Cardiology, Childrens Hospital of Los Angeles, Los Angeles, CA, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Wood
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Cohen
authors.affiliation: Department of Biostatistics, University of Texas Health Science Center, Houston, TX, USA.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Pressel
authors.affiliation: Department of Pediatrics, Cohen Children's Medical Center of NY, New Hyde Park, NY, USA.
authors.forename: Banu
authors.initials: B
authors.lastname: Aygun
authors.affiliation: Department of Pediatrics, University of South Alabama, Mobile, AL, USA.
authors.forename: Hamayun
authors.initials: H
authors.lastname: Imran
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnnati, OH, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Luchtman-Jones
authors.affiliation: Department of Pediatrics, Anna and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Thompson
authors.affiliation: Department of Biostatistics, University of Texas Health Science Center, Houston, TX, USA.
authors.forename: Beng
authors.initials: B
authors.lastname: Fuh
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnnati, OH, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Schultz
authors.affiliation: Department of Biostatistics, University of Texas Health Science Center, Houston, TX, USA.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Davis
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnnati, OH, USA.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D000986:Antisickling Agents / Q000627:therapeutic use; D002648:Child; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000627:therapeutic use; D019190:Iron Overload / Q000209:etiology* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D010179:Pancreas / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D065227:Transfusion Reaction; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D000986:Antisickling Agents; D007502:Iron Chelating Agents; D005293:Ferritins; D007501:Iron; D006918:Hydroxyurea
keywords: MRI; iron overload; sickle cell anaemia; sickle cell radiology; transfusions