Organ iron accumulation in chronically transfused children with sickle cell anaemia

Baseline results from the TWiTCH trial

John C. Wood*, Alan R. Cohen, Sara L. Pressel, Banu Aygun, Hamayun Imran, Lori Luchtman-Jones, Alexis A Thompson, Beng Fuh, William H. Schultz, Barry R. Davis, Russell E. Ware, Alex George, Brigitta U. Mueller, Matthew M. Heeney, Theodosia A. Kalfa, Stephen Nelson, R. Clark Brown, Beatrice Gee, Janet L. Kwiatkowski, Kim Smith- Whitley & 19 others Isaac Odame, Jennifer Webb, Elizabeth Yang, Margaret T. Lee, Connie Piccone, Sherron M. Jackson, Sharon Singh, Kerri Nottage, Jane S. Hankins, Scott T. Miller, Lee Hilliard, Ofelia Alvarez, Melissa Rhodes, Zora R. Rogers, Sharada A. Sarnaik, William C. Owen, Cynthia Gauger, Carla Roberts, Jennifer A. Rothman

*Corresponding author for this work

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 (r2 = 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.

Original languageEnglish (US)
Pages (from-to)122-130
Number of pages9
JournalBritish Journal of Haematology
Volume172
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Hydroxyurea
Sickle Cell Anemia
Iron
Kidney
Iron Overload
Liver
Primary Prevention
Transferrin
Ferritins
Hemolysis
Reperfusion Injury
Pancreas
Albumins
Creatinine
Hemoglobins
Oxidative Stress
Spleen
Stroke
Outcome Assessment (Health Care)
Urine

Keywords

  • Iron overload
  • MRI
  • Sickle cell anaemia
  • Sickle cell radiology
  • Transfusions

ASJC Scopus subject areas

  • Hematology

Cite this

Wood, J. C., Cohen, A. R., Pressel, S. L., Aygun, B., Imran, H., Luchtman-Jones, L., ... Rothman, J. A. (2016). Organ iron accumulation in chronically transfused children with sickle cell anaemia: Baseline results from the TWiTCH trial. British Journal of Haematology, 172(1), 122-130. https://doi.org/10.1111/bjh.13791
Wood, John C. ; Cohen, Alan R. ; Pressel, Sara L. ; Aygun, Banu ; Imran, Hamayun ; Luchtman-Jones, Lori ; Thompson, Alexis A ; Fuh, Beng ; Schultz, William H. ; Davis, Barry R. ; Ware, Russell E. ; George, Alex ; Mueller, Brigitta U. ; Heeney, Matthew M. ; Kalfa, Theodosia A. ; Nelson, Stephen ; Clark Brown, R. ; Gee, Beatrice ; Kwiatkowski, Janet L. ; Smith- Whitley, Kim ; Odame, Isaac ; Webb, Jennifer ; Yang, Elizabeth ; Lee, Margaret T. ; Piccone, Connie ; Jackson, Sherron M. ; Singh, Sharon ; Nottage, Kerri ; Hankins, Jane S. ; Miller, Scott T. ; Hilliard, Lee ; Alvarez, Ofelia ; Rhodes, Melissa ; Rogers, Zora R. ; Sarnaik, Sharada A. ; Owen, William C. ; Gauger, Cynthia ; Roberts, Carla ; Rothman, Jennifer A. / Organ iron accumulation in chronically transfused children with sickle cell anaemia : Baseline results from the TWiTCH trial. In: British Journal of Haematology. 2016 ; Vol. 172, No. 1. pp. 122-130.
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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 (r2 = 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.",
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author = "Wood, {John C.} and Cohen, {Alan R.} and Pressel, {Sara L.} and Banu Aygun and Hamayun Imran and Lori Luchtman-Jones and Thompson, {Alexis A} and Beng Fuh and Schultz, {William H.} and Davis, {Barry R.} and Ware, {Russell E.} and Alex George and Mueller, {Brigitta U.} and Heeney, {Matthew M.} and Kalfa, {Theodosia A.} and Stephen Nelson and {Clark Brown}, R. and Beatrice Gee and Kwiatkowski, {Janet L.} and {Smith- Whitley}, Kim and Isaac Odame and Jennifer Webb and Elizabeth Yang and Lee, {Margaret T.} and Connie Piccone and Jackson, {Sherron M.} and Sharon Singh and Kerri Nottage and Hankins, {Jane S.} and Miller, {Scott T.} and Lee Hilliard and Ofelia Alvarez and Melissa Rhodes and Rogers, {Zora R.} and Sarnaik, {Sharada A.} and Owen, {William C.} and Cynthia Gauger and Carla Roberts and Rothman, {Jennifer A.}",
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Wood, JC, Cohen, AR, Pressel, SL, Aygun, B, Imran, H, Luchtman-Jones, L, Thompson, AA, Fuh, B, Schultz, WH, Davis, BR, Ware, RE, George, A, Mueller, BU, Heeney, MM, Kalfa, TA, Nelson, S, Clark Brown, R, Gee, B, Kwiatkowski, JL, Smith- Whitley, K, Odame, I, Webb, J, Yang, E, Lee, MT, Piccone, C, Jackson, SM, Singh, S, Nottage, K, Hankins, JS, Miller, ST, Hilliard, L, Alvarez, O, Rhodes, M, Rogers, ZR, Sarnaik, SA, Owen, WC, Gauger, C, Roberts, C & Rothman, JA 2016, 'Organ iron accumulation in chronically transfused children with sickle cell anaemia: Baseline results from the TWiTCH trial', British Journal of Haematology, vol. 172, no. 1, pp. 122-130. https://doi.org/10.1111/bjh.13791

Organ iron accumulation in chronically transfused children with sickle cell anaemia : Baseline results from the TWiTCH trial. / Wood, John C.; Cohen, Alan R.; Pressel, Sara L.; Aygun, Banu; Imran, Hamayun; Luchtman-Jones, Lori; Thompson, Alexis A; Fuh, Beng; Schultz, William H.; Davis, Barry R.; Ware, Russell E.; George, Alex; Mueller, Brigitta U.; Heeney, Matthew M.; Kalfa, Theodosia A.; Nelson, Stephen; Clark Brown, R.; Gee, Beatrice; Kwiatkowski, Janet L.; Smith- Whitley, Kim; Odame, Isaac; Webb, Jennifer; Yang, Elizabeth; Lee, Margaret T.; Piccone, Connie; Jackson, Sherron M.; Singh, Sharon; Nottage, Kerri; Hankins, Jane S.; Miller, Scott T.; Hilliard, Lee; Alvarez, Ofelia; Rhodes, Melissa; Rogers, Zora R.; Sarnaik, Sharada A.; Owen, William C.; Gauger, Cynthia; Roberts, Carla; Rothman, Jennifer A.

In: British Journal of Haematology, Vol. 172, No. 1, 01.01.2016, p. 122-130.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Organ iron accumulation in chronically transfused children with sickle cell anaemia

T2 - Baseline results from the TWiTCH trial

AU - Wood, John C.

AU - Cohen, Alan R.

AU - Pressel, Sara L.

AU - Aygun, Banu

AU - Imran, Hamayun

AU - Luchtman-Jones, Lori

AU - Thompson, Alexis A

AU - Fuh, Beng

AU - Schultz, William H.

AU - Davis, Barry R.

AU - Ware, Russell E.

AU - George, Alex

AU - Mueller, Brigitta U.

AU - Heeney, Matthew M.

AU - Kalfa, Theodosia A.

AU - Nelson, Stephen

AU - Clark Brown, R.

AU - Gee, Beatrice

AU - Kwiatkowski, Janet L.

AU - Smith- Whitley, Kim

AU - Odame, Isaac

AU - Webb, Jennifer

AU - Yang, Elizabeth

AU - Lee, Margaret T.

AU - Piccone, Connie

AU - Jackson, Sherron M.

AU - Singh, Sharon

AU - Nottage, Kerri

AU - Hankins, Jane S.

AU - Miller, Scott T.

AU - Hilliard, Lee

AU - Alvarez, Ofelia

AU - Rhodes, Melissa

AU - Rogers, Zora R.

AU - Sarnaik, Sharada A.

AU - Owen, William C.

AU - Gauger, Cynthia

AU - Roberts, Carla

AU - Rothman, Jennifer A.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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 (r2 = 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.

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KW - Iron overload

KW - MRI

KW - Sickle cell anaemia

KW - Sickle cell radiology

KW - Transfusions

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