Liver iron and serum ferritin levels are misleading for estimating cardiac, pancreatic, splenic and total body iron load in thalassemia patients: factors influencing the heterogenic distribution of excess storage iron in organs as identified by MRI T2*

Abstract

A comparative assessment of excess storage iron distribution in the liver, heart, spleen and pancreas of β-thalassemia major (β-ΤΜ) patients has been carried out using magnetic resonance imaging (MRI) relaxation times T2*. The β-ΤΜ patients (8-40 years, 11 males, 9 females) had variable serum ferritin levels (394-5603 μg/L) and were treated with deferoxamine (n = 10), deferiprone (n = 5) and deferoxamine/deferiprone combination (n = 5). MRI T2* assessment revealed that excess iron is not proportionally distributed among the organs but is stored at different concentrations in each organ and the distribution is different for each β-ΤΜ patient. There is random variation in the distribution of excess storage iron from normal to severe levels in each organ among the β-ΤΜ patients by comparison to the same organs of ten normal volunteers. The correlation of serum ferritin with T2* was for spleen (r = -0.81), liver (r = -0.63), pancreas (r = -0.33) and none with heart. Similar trend was observed in the correlation of liver T2* with the T2* of spleen (r = 0.62), pancreas (r = 0.61) and none with heart. These studies contradict previous assumptions that serum ferritin and liver iron concentration is proportional to the total body iron stores in β-ΤΜ and especially cardiac iron load. The random variation in the concentration of iron in the organs of β-ΤΜ patients appears to be related to the chelation protocol, organ function, genetic, dietary, pharmacological and other factors. Monitoring of the iron load for all the organs is recommended for each β-ΤΜ patient.

Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases

“…Variations in compensatory mechanisms and alternative metabolic pathways which are in operation in affected cells and tissues may contribute to minimising the severity of FA [85] . Similar variations are observed in other inherited and metabolic diseases including TM and hereditary haemochromatosis [13,62,[85][86][87] . Deficit of frataxin is mostly related to many abnormalities associated with mitochondrial structure and function.…”

“…The quality of life and survival of TM patients have increased substantially in the last 20 years as a consequence of the introduction of effective therapeutic postnatal measures and especially diagnostic advances in the estimation of iron overload using the MRI T2* and T2 techniques and especially the effective treatment of iron overload with L1 and its combinations [86,132] . These changes and related improvements are more obvious in Cyprus and other countries where government health authority intervention is significant and appropriate by-laws as well as appropriate procedures are implemented using effective organisational health structures.…”

Early detection of cardiac involvement in thalassemia: From bench to bedside perspective

“…Patients with mild, moderate and severe cardiac iron overload (T2* 12-20, 8-12 and less than 8 ms, respectively) had impaired LVEF in [56] (r 2 = 0.003, P = 0.04) TM/776 patients Retrospective Significant relationship between cardiac R2* and ferritin / Marsella et al [59] (r = -0.359, P < 0.0001) TM/167 patients Prospective Myocardial T2* was correlated with serum ferritin / Tanner et al [60] (r = -0.34, P < 0.001) TM/19 patients, SCD/17 patients Cross sectional Cardiac 1/T2* was correlated with ferritin level / Wood et al [61] (r 2 = 0.33, P = 0.01) TM/106 patients Prospective No significant correlation between heart T2* and serum ferritin × Anderson et al [16] TM/60 patients Prospective Serum ferritin did not correlate with cardiac iron values × Merchant et al [57] TM/20 patients Prospective No correlation between serum ferritin and cardiac T2* × Kolnagou et al [58] TM/47 patients Retrospective Cardiac T2* was not associated with the serum ferritin × Bayraktaroğlu et al [22] TM: Thalassemia major; SCD: Sickle cell disease. TM/776 patients Retrospective Significant correlation between LVEF and cardiac R2* (r = -0.327, P < 0.0001) / Marsella et al [59] TM/106 patients Prospective Significant correlation of myocardial T2* below 20 ms with LVEF (r = 0.61, P < 0.0001), LVESVi (r = 0.50, P < 0.0001), and LV mass index (r = 0.40, P < 0.001) / Anderson et al [16] TM/167 patients Prospective Significant relationship between myocardial iron and LVEF (r = 0.57, P < 0.001) / Tanner et al [60] TM/67 patients Cross sectional Myocardial T2* related to LV diastolic function (EPFR, r = -0.20, P = 0.19; APFR, r = 0.49, P < 0.001; EPFR/APFR ratio, r = -0.62, P < 0.001) / Westwood et al [52] TM/33 patients Cross sectional Good correlation of DT, Tei index and E/Em index with cardiac T2* values (P < 0.05, r = 0.70-0.81) and weak correlation of E/A with T2* (P < 0.05, r = -0.44) / Barzin et al [84] TM/47 patients Retrospective Significant correlations of the myocardial T2* with LVESVi and LVEDVi (r = -0.32, P = 0.027; r = -0.29, P = 0.046, respectively) / Bayraktaroğlu et al [22] TM/19 patients, SCD/17 patients…”

“…Several studies indicated that serum ferritin was not correlated with cardiac T2* [16,22,57,58] . However, other studies with larger population size showed a weak relationship between serum ferritin and heart T2* [56,[59][60][61] .…”

Effect of Iron Chelation Therapy on Glucose Metabolism in Non-Transfusion-Dependent Thalassaemia

“…Although liver iron is a surrogate for total body iron burden and has been used for years to monitor chelation therapy among thalassaemia patients, it is a poor predictor of cardiac iron status [22]. The extrahepatic tissues of the pancreas and heart selectively load circulating NTBI, which is different from the hepatic iron load with transferrin-bound iron [23].…”