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.

Keywords: MRI; iron overload; sickle cell anaemia; sickle cell radiology; transfusions.

Figure 1

(Left) Representative transverse slice from the T2* acquisition with the liver, spleen and pancreas outlined. Iron has caused the liver and spleen to appear quite dark relative to the other abdominal tissues. (Right) Representative coronal slice demonstrating typical pattern of cortical darkening caused by filtered haemoglobin depositing in the proximal and distal tubules of the kidney.

Figure 2

Illustration of close proximity of gastric air to pancreas in some patients; this caused artifactual increases in pancreas R2* in four patients.

Figure 3

Scattergram depicting splenic R2* versus liver iron concentration. Both axes have a logarithmic scale.

Figure 4

Bar graph depicting the kidney R2* value in patients with and without proteinuria, defined as a urinary albumin-creatinine ratio (ACR) greater than 30. Error bars represent standard error of the mean.