Diamond Blackfan Anaemia Patients Have a Higher Rate of Hepatic Iron Accumulation Than Thalassaemia Major Patients Leading to Fibrosis

Abstract 997

Diamond Blackfan anaemia is an inherited bone marrow failure syndrome with haematological and systemic manifestations. The classical presentation of the condition is the development of anaemia in infancy, which occurs in approximately 85–90% of the patients. Long-term 40% require transfusions as they fail to maintain erythropoiesis at acceptable doses of steroids and only approximately 10% of the patients go into remission. To investigate the iron load caused by transfusions and its effect we studied the liver biopsies of 13 patients with DBA and compared them with 27 patients suffering from thalassaemia major (TM). The findings were correlated with the number of transfusions, chelation treatment, ferritin level and MR techniques. Image analysis of the degree of fibrosis was performed using NIS-elements software after staining liver biopsy slides with Sirius Red.

TM patients were significantly older [median age: TM 9 years (3–18), DBA 5 years (1–15); p=0.004], which was also reflected in the duration (months) of transfusion [TM 105 (12–198), DBA 52 (12–130); p=0.004]. However, there was no difference in the frequency of transfusions (p=0.51) and in the length of time (months) between starting transfusions and chelation (TM 19, DBA 27; p=0.08). DBA patients received proportionately more chelation per transfusion than TM patients at the time of biopsy (TM 1.24, DBA 1.58; p=0.015). Ferritin levels were higher in TM patients, though not significant [TM 2028 μg/L (1292–4901), DBA 1324 μg/L (535–2300); p=0.16).

Despite having significantly fewer transfusions, the grade of iron deposition was higher in the DBA group (TM 2, DBA 3; p=0.035). This was also reflected in MRI T2* quantitation, which demonstrated a higher hepatic iron load in DBA patients [TM 3 ms (1–12), DBA 2 ms (1–3); p=0.59]. The rate of biochemical iron accumulation (mg/g DW) for every month of transfusion was significantly higher in the DBA group (TM 0.05, DBA 0.11; p=0.005). The rate of fibrosis accumulation was 60% higher in the DBA group, although this was not statistically significant (TM 0.1, DBA 0.16; p=0.07) and could be due to a time lag between iron accumulation and fibrosis formation, particularly as the DBA patients were younger and had had shorter follow up. Biochemical iron, ferritin level and MRI T2* had low, significant correlations with fibrosis in TM patients (0.547, p=0.001; 0.357, p=0.033; −0.430, p=0.011, respectively) and FerriScan in DBA patients (0.75, p=0.05). In conclusion, DBA patients have a higher rate of iron accumulation with a trend to higher hepatic fibrosis.