Hepatic Iron Overload in Children With Sickle Cell Anemia on Chronic Transfusion Therapy

Abstract

Hepatic iron overload is a serious complication of chronic transfusion therapy in patients with sickle cell disease (SCD). No firm consensus has been reached with regard to correlation between hepatic iron content (HIC) and variables including age, number of transfusions, and serum iron makers. Also, the role of HIC in determining hepatic injury is not well established. There is scarcity of data on chronically transfused children with SCD and no other confounding liver pathology. We aimed to further explore relationships between these variables in a cohort of children with SCD on chronic transfusion therapy naive to chelation. Liver biopsies obtained before starting chelation therapy from 27 children with sickle cell anemia receiving chronic transfusion therapy were evaluated for histologic scoring and determination of HIC. Average serum ferritin and iron saturation values were determined for 6 months before biopsy. Duration and total volume of transfusion were obtained from the medical records. All children were negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infections. Mean age at biopsy was 10.95+/-3.34 years. Mean duration and total volume of transfusions were 50.0+/-26.6 months and 17.4+/-9.6 L, respectively. Pearson product-moment bivariate correlation coefficients indicated significant correlations between HIC and histologic iron score, serum ferritin, iron saturation, age, and transfusion volume. After adjusting for transfusion volume, a significant correlation was only seen between HIC and transfusion volume. Mean HIC was 21.8+/-10.4 mg/g dry weight, with fibrosis observed in 10 patients and lobular inflammation in 9. HIC was higher in biopsies with fibrosis (28.2+/-3.8 mg/g) than biopsies without fibrosis (17.6+/-18.3 mg/g; P=0.012). HIC did not differ between biopsies with lobular inflammation (25.5+/-4.0 mg/g) and biopsies without inflammation (19.9+/-2.5 mg/g; P=0.22). These findings show that transfusion volume provides more insight on hepatic iron overload than serum iron markers.

Deferiprone versus Deferoxamine in Sickle Cell Disease: Results from a 5-year long-term Italian multi-center randomized clinical trial

“…4). This last finding is similar to that reported by Brown et al, 2009 [10] who showed relationship between hepatic iron content and the transfusion volume in 27 children with sickle cell anemia receiving chronic transfusion therapy [10] .…”

Retrospective comparison of gradient recalled echo R2* and spin-echo R2 magnetic resonance analysis methods for estimating liver iron content in children and adolescents

“…With ongoing, severe iron loading, non-transferrin-bound iron forms and accumulates in the liver and other organs, such as endocrine glands and the heart, where tissue-damaging free radicals are formed. Untreated, iron overload causes hepatic fibrosis and cirrhosis, diabetes mellitus, hypogonadism, cardiomyopathy, dysrhythmias and sudden death [3][4][5].…”

Guidelines on red cell transfusion in sickle cell disease. Part I: principles and laboratory aspects

“…Simple transfusion inevitably causes greater positive iron balance than exchange transfusion (Cohen et al, 1992;Kim et al, 1994;Adams et al, 1996;Hilliard et al, 1998;Harmatz et al, 2000;Olivieri, 2001;Brown et al, 2009). Iron accumulation in exchange transfusion depends on the difference between the numbers of red cells removed and those given and is influenced by the type of exchange (manual or automated), as well as Hb and %HbS values pre-and postexchange transfusion (Porter & Garbowski, 2013).…”