Cardiac and pancreatic iron overload evaluation of sickle/β-Thalassemia patients utilizing T2* MRI

Introduction

Transfusion-dependent hemolytic anemias in particular thalassemia major and sickle cell disease require multiple transfusions in order to avoid chronic anemia sequelae. This regimen entails intrinsic deleterious effects, the majority of which are related to iron deposition in the reticuloendothelial system. Thus, iron is deposited in myocardial, hepatic and endocrine gland tissues. Both Ferrtin level and liver biopsies have no predictive values for cardiac iron deposition levles.

T2* MRI sequences have been used for reliable evaluation of iron load in the heart, liver and pancreas. Patients with no iron overload have normal cardiac function whereas those with cardiac iron deposition suffer from myocardial dysfunction and arrhythmias.

Purpose

To quantify iron content in the heart, liver and pancreas of sickle/β-thalassemia patients.

Methods

Multicenter evaluation of eleven patients with sickle/β-thalassemia was performed (3 males; 8 females, mean age 31 years). Mean hemoglobin: 9.0 gr/dl; Serum ferritin: 3900 ng/ml; Transferrin saturation: 80%. All patients were multitranfused with an average of 97 packed cell units. One patient was treated with iron chelation for 10 months. Seven patients received daily Hydoxy-Urea for > 10 years.

MRI (1.5 T, GE MRI system) sequences included: Steady-state free precession (SSFP) for left ventricular ejection fraction (LVEF) evaluation; Breath-hold T2* multi echo gradient for iron load quantification, sampled across regions of interest in the LV septum, liver parenchyma and pancreatic tissue.

Results

All patients had normal cardiac and pancreatic T2* values (>20 ms and >30 ms, respectively). Normal cardiac function was demonstrated in all patients (LVEF, LV endsystolic and endiastolic volumes).

Seven patients demonstrated evidence of mild to moderate hepatic iron deposition (T2* <6.3 ms). In these patients mean serum ferritin (5656 ng/ml) and transferrin saturation (92.4%) were significantly higher (p = 0.001) compared with the 4 patients with normal hepatic T2* levels.

Conclusion

T2* MRI sequences allow non invasive, repeated iron deposition quantification in multitransfused patients. In our cohort of eleven patients with sickle/β-thalassemia, no cardiac or pancreatic iron deposition was demonstreted. Mild to moderate iron liver deposition was found in 7 of these patients, in which serum ferritin levels and transferrin saturation were significantly higher.

With respect to iron deposition, multitransfused sickle/β-thalassemia are similar to patients with homozygous sickle cell disease and not to patients with thalassemia major. The reasons for this observation are still unclear. This similarity could be related in part to the relativly low number of transfusions, starting later in life, in these patients.

The liver is the dominant iron storage organ. Hepatic iron concentration correlates closely with the total body iron content. While iron uptake by hepatocytes is predominately mediated via transferrin and correlates well with serum ferritin levels, as confirmed in the present study, this is not the case in cardiac and endocrine iron uptake regulation. These organs might acquire the excess metal differently.