Tissue iron evaluation in chronically transfused children shows significant levels of iron loading at a very young age

Abstract

Chronic blood transfusions start at a very young age in subjects with transfusion-dependent anemias, the majority of whom have hereditary anemias. To understand how rapidly iron overload develops, we retrospectively reviewed 308 MRIs for evaluation of liver, pancreatic, or cardiac iron in 125 subjects less than 10 years old. Median age at first MRI evaluation was 6.0 years. Median liver iron concentrations in patients less than 3.5 years old were 14 and 13 mg/g dry weight in thalassemia major (TM) and Diamond-Blackfan anemia (DBA) patients, respectively. At time of first MRI, pancreatic iron was markedly elevated (> 100 Hz) in DBA patients, and cardiac iron (R * 2 >50 Hz) was present in 5/112 subjects (4.5%), including a 2.5 years old subject with DBA. Five of 14 patients (38%) with congenital dyserythropoietic anemia (CDA) developed excess cardiac iron before their 10th birthday. Thus, clinically significant hepatic and cardiac iron accumulation occurs at an early age in patients on chronic transfusions, particularly in those with ineffective or absent erythropoiesis, such as DBA, CDA, and TM, who are at higher risk for iron cardiomyopathy. Performing MRI for iron evaluation in the liver, heart, and pancreas as early as feasible, particularly in those conditions in which there is suppressed bone marrow activity is very important in the management of iron loaded children in order to prescribe appropriate chelation to prevent long-term sequelae. Am. J. Hematol. 88:E283-E285,

Comparison of various iron chelators and prochelators as protective agents against cardiomyocyte oxidative injury

“…Of note, the most important beneficial effect of Fe chelation therapy has been attributed to the prevention of cardiac mortality due to Fe-catalyzed and ROS-mediated cardiomyopathy [36–38]. Fe-mediated free radical injury is also attributed to cardiac myocyte apoptosis in other pathological conditions not associated with systemic Fe overload, such as ischemia/reperfusion injury, myocardium remodeling after myocardial infarction and heart failure [39–42].…”

Guidelines for quantifying iron overload

“…Nonetheless, there is expanding monitoring and treatment experience in beta thalassemia intermedia, SCD, myelodysplasia, and other rare anemias. 33,34 The risk of cardiac iron overload varies with the degree of effective erythropoiesis, among other factors, being most common in Blackfan-Diamond syndrome 33,34 and least common in SCD 22,35 and thalassemia intermedia. 33,36 Chronically transfused Blackfan-Diamond patients are particularly vulnerable to extrahepatic iron deposition 34 and require close monitoring in the first decade of life.…”

Physiology and pathophysiology of iron in hemoglobin-associated diseases

“…Thus, loading of NTBI/LPI into the spleen and pancreas via DMT1 does not decrease in response to high iron [10]. This, in combination with pancreatic ZIP14 [9, 30], may explain why rapid pancreas iron loading is observed in humans soon after liver iron increases [75]. …”

“…The molecular mechanisms are not well worked out yet in humans. However, the ability of the liver to load both TBI and NTBI may explain the very rapid loading of iron in the liver in humans [75, 78]. …”

“…Blackfan-Diamond syndrome is a congenital pure red cell aplasia, with few if any red cell precursors in the marrow. About 20% of the patients will become transfusion-dependent [115, 116] and have early development of cardiac iron [75]. Myelodysplasia is a pre-malignant marrow failure syndrome that can occur at any age, but more commonly presents after the fourth or fifth decades of life.…”