Transfusion-related iron overload in survivors of childhood cancer.

Guidelines for the monitoring and management of iron overload in patients with haemoglobinopathies and rare anaemias.

Hfe Acts in Hepatocytes to Prevent Hemochromatosis

Future challenges in the use of magnetic resonance imaging for the diagnosis of iron overload.

Non-invasive assessment of hepatic iron overload: are we finally there?

A Prospective Study of Iron Overload in Patients Undergoing Ablative Stem Cell Transplantation.

Serial Measurements of Cardiac and Hepatic Iron with MRI T2* In Transfusion Dependent Patients with Beta-Thalassemia Major Receiving Deferasirox

Phlebotomy for Pediatric and Young Adult Oncology Patients Treats Transfusional Iron Overload

Changes in MRI-Estimated Cardiac and Hepatic Iron Load in β-Thalassemia Patients Treated with Deferasirox at a Single Institution

Increased prevalence and severity of cardiac iron overload in transfusion dependent diamond-blackfan anemia syndrome caused by small versus large ribosomal subunit mutations

Serum ferritin and total units transfused for assessing iron overload in adults with sickle cell disease

A 5-Years Follow-up in Deferasirox Treatment: Improvement of Cardiac and Hepatic Iron Overload and Amelioration in Cardiac Function in Thalassemia Major Patients

The use of magnetic resonance imaging (MRI) to detect organ-specific iron overload is becoming increasingly common. Although hepatic iron overload has been recognized in patients with sickle cell disease (SCD), cardiac iron deposition has only been examined in a few reports. This was a cross-sectional study of 23 patients with SCD. Patient charts were reviewed and data collected for drug use, total lifetime transfusions (TLT), transfusion rate (TR), status of the spleen, and comorbid illnesses or infections. Blood samples were obtained for assessment of hemoglobin, serum ferritin, non-transferrin-bound iron (NTBI), and liver enzyme levels. Doppler echocardiography was performed to detect pulmonary hypertension (PHT) and assess left ventricular ejection fraction. Cardiac iron levels were measured by MRI T2*. Direct determination of liver iron concentration (LIC) was performed using R2 MRI. In this study, cardiac T2* >20 ms was considered normal. The mean age was 24.4 +/- 9.7 yr, with a male to female ratio of 15:8. A total of 9 (49.9%) patients were splenectomized. The mean TR was 14.1 +/- 13.2 Units/yr, and the mean hemoglobin level was 9.0 g/dL. PHT was detected in 6 (27.3%) patients, but none had evidence of heart failure. The mean serum ferritin, LIC, and NTBI levels were 997.7 ng/mL, 4.6 mg Fe/g dw, and 1.1 +/- 2.2, respectively. TR was a much better predictor of iron burden (LIC, ferritin, NTBI) than TLT. In fact, TR less than 10 Units/yr did not produce significant iron overload reflecting spontaneous losses as high as 0.11 mg/kg/d. None of the patients had evidence of cardiac iron overload (mean cardiac T2* = 37.3 +/- 6.2 ms; range: 21.9-46.8 ms). There was also no statistically significant correlation between cardiac T2* values and any of the study variables. Our study demonstrates that TR is a stronger predictor of iron overload than TLT. It also confirms cardiac sparing in patients with SCD, even in subjects with significant transfusion burden, systemic and hepatic iron overload.

Iron overload causes most of the mortality and morbidity associated with thalassemia. Excess iron deposits primarily in the liver, but once a threshold level is reached, iron loading may occur in other tissues such as the heart. Magnetic resonance imaging is a well established technique to noninvasively quantify myocardial and liver iron content. More than 300 disease-causing mutations have been identified. We aimed to determine the impact of genotype on liver iron content in patients with beta thalassemia. Cross sectional study was carried on 73 patients with beta thalassemia. MRI liver and heart was performed to determine hepatic and myocardial iron overload. Genotyping was determined by DNA sequencing technique. The mean liver iron content was 17.4mg/g dw and mean cardiac T2* was 25.5ms in our patients. Patients with β0β0 were associated with significantly higher liver and myocardial iron content compared to those with β0β+ and β+β+ genotypes. There was a clear association between genotype and both hepatic and myocardial iron overload. Patients with β0β0 had significantly higher liver and heart iron content compared to those with β0β+ and β+β+ genotypes. Liver iron content was strongly correlated to serum ferritin levels and myocardial iron overload.

Transient Elastography of Liver in Hb E Beta Thalassemia: A Novel Tool to Determine Hepatic Iron Overload?

IntroductionChronic blood transfusion is the mainstay of care for individuals with β-thalassemia major (BTM). However, it causes iron-overload that requires monitoring and management by long-term iron chelation therapy to prevent endocrinopathies and cardiomyopathies, which can be fatal. Hepatic R2 MRI method (FerriScan®) has been validated as the gold standard for evaluation and monitoring liver iron concentration (LIC) that reflects the total body iron-overload. Although adequate oral iron chelation therapy (OIC) is promising for the treatment of transfusional iron-overload, some patients are less compliant with it, and others suffer from long-term effects of iron overload.ObjectiveThe aim of our study was to evaluate the prevalence of endocrinopathies and liver dysfunction, in relation to LIC and serum ferritin level, in a selected group of adolescents and young adult BTM patients with severe hepatic iron overload (LIC from 15 to 43 mg Fe/g dry weight).Patients and MethodsTwenty-four selected BTM patients with severe LIC, due to transfusion-related iron-overload, followed at the Haematology Section, National Centre for Cancer Care and Research, Hamad Medical Corporation of Doha (Qatar), from April 2015 to July 2017, were retrospectively evaluated. The prevalence of short stature, hypogonadism, hypothyroidism, hypoparathyroidism, impaired fasting glucose (IFG), diabetes, and adrenal insufficiency was defined and assessed according to the International Network of Clinicians for Endocrinopathies in Thalassemia (ICET) and American Diabetes Association criteria.ResultsPatients’ most common transfusion frequency was every three weeks (70.8%). At the time of LIC measurements, their median age was 21.5 years with a mean age of 21.7 ± 8.0 years. Mean LIC was 32.05 ± 10.53 mg Fe/g dry weight (range: 15 to 43 mg Fe/g dry weight), and mean serum ferritin level was 4,488.6 ± 2,779 μg/L. LIC was correlated significantly with serum ferritin levels (r = 0.512; p = 0.011). The overall prevalence of short stature was 26.1% (6/23), IFG was 16.7% (4/24), sub-clinical hypothyroidism was 14.3% (3/21), hypogonadotropic hypogonadism was 14.3% (2/14), diabetes mellitus was 12.5% (3/24), and biochemical adrenal insufficiency was 6.7% (1/15). The prevalence of hepatitis C positivity was 20.8% (5/24). No case of clinical hypothyroidism, adrenal insufficiency or hypoparathyroidism was detected in this cohort of patients. The prevalence of IFG impaired fasting glucose was significantly higher in BTM patients with very high LIC (>30 mg Fe/g dry liver) versus those with lower LIC (p = 0.044). The prevalence of endocrinopathies was not significantly different between the two groups of patients with LIC above and below 15 mg Fe/g dry weight.ConclusionsA significant number of BTM patients, with high LIC and endocrine disorders, still exist despite the recent developments of new oral iron chelating agents. Therefore, physicians’ strategies shall optimize early identification of those patients to optimise their chelation therapy and to avoid iron-induced organ damage. We believe that further studies are needed to evaluate if serial measurements of quantitative LIC may predict the risk for endocrine complications. Until these data are available, we recommend a close monitoring of endocrine and other complications, according to the international guidelines.