Measurements of hepatic iron concentration (HIC) are important predictors of transfusional iron burden and long-term outcome in patients with transfusion-dependent anemias. The goal of this work was to develop a readily available, noninvasive method for clinical HIC measurement. The relaxation rates R2 (1/T2) and R2^* (1/T2^*) measured by magnetic resonance imaging (MRI) have different advantages for HIC estimation. This article compares noninvasive iron estimates using both optimized R2 and R2^* methods in 102 patients with iron overload and 13 controls. In the iron-overloaded group, 22 patients had concurrent liver biopsy. R2 and R2^* correlated closely with HIC (r² ≥ .95) for HICs between 1.33 and 32.9 mg/g, but R2 had a curvilinear relationship to HIC. Of importance, the R2 calibration curve was similar to the curve generated by other researchers, despite significant differences in technique and instrumentation. Combined R2 and R2^* measurements did not yield more accurate results than either alone. Both R2 and R2^* can accurately measure hepatic iron concentration throughout the clinically relevant range of HIC with appropriate MRI acquisition techniques. (Blood. 2005;106:1460-1465)

Although sickle cell disease (SCD) is marked by high utilization of medical resources, the full cost of care for patients with SCD, including care not directly related to SCD, is unknown. The purpose of this study was to estimate the total cost of medical care for a population of children and adults with SCD. We used data from individuals diagnosed with SCD enrolled in the Florida Medicaid program during 2001–2005 to estimate total, SCD‐related, and non‐SCD‐related cost per patient‐month based on patient age at the time of health care use. Across the 4,294 patient samples, total health care costs generally rose with age, from $892 to $2,562 per patient‐month in the 0–9‐ and 50–64‐year age groups, respectively. Average cost per patient‐month was $1,389. Overall, 51.8% of care was directly related to SCD, the majority of which (80.5%) was associated with inpatient hospitalizations. Notably, non‐SCD‐related costs were substantially higher than those reported for the general US population. These results suggest a discounted (3% discount rate) lifetime cost of care averaging $460,151 per patient with SCD. Interventions designed to prevent SCD complications and avoid hospitalizations may reduce the significant economic burden of the disease. Am. J. Hematol. 2009.

Cardiac T2* (magnetic resonance imaging relaxation parameter) is abnormally low in approximately 40% of adults with thalassemia major (TM), suggesting myocardial iron deposition, but it is unknown at what age this occurs. To address this question, we measured cardiac T2* and function in 19 young patients (aged 7-26 years) with TM as well as 17 patients receiving long-term transfusions for sickle cell anemia (SCA) matched for age, sex, and liver iron content. Cardiac T2* was normal in all of the SCA patients but was low (high iron) in 8 of 19 TM patients. Abnormal T2* was observed only in the TM patients receiving transfusions for 13 years or longer and was correlated with ferritin but not liver iron levels. Cardiac dysfunction was present in 3 of the 8 patients with low T2*. Cardiac T2* changes have a long latency relative to liver iron accumulation. Total transfusional burden is a significant independent risk factor for low cardiac T2* and may partially account for differences observed between patients with SCA and TM.

Summary: Deferasirox is a once‐daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open‐label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non‐progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11·4%) and deferoxamine (11·1%) were similar. Over 1 year, similar dose‐dependent LIC reductions were observed with deferasirox and deferoxamine. Once‐daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.

High hepatic iron concentration (HIC) is associated with cardiac iron overload. However, simultaneous measurements of heart and liver iron often demonstrate no significant linear association. We postulated that slower rates of cardiac iron accumulation and clearance could reconcile these differences. To test this hypothesis, we examined the longitudinal evolution of cardiac and liver iron in 38 thalassemia major patients, using previously validated magnetic resonance imaging (MRI) techniques. On cross-sectional evaluation, cardiac iron was uncorrelated with liver iron, similar to previous studies. However, relative changes in heart and liver iron were compared with one another using a metric representing the temporal delay between them. Cardiac iron significantly lagged liver iron changes in almost half of the patients, implying a functional but delayed association. The degree of time lag correlated with initial HIC (r = 0.47, P < .003) and initial cardiac R2* (r = 0.57, P < .001), but not with patient age. Thus, longitudinal analysis confirms a lag in the loading and unloading of cardiac iron with respect to liver iron, and partially explains the weak cross-sectional association between these parameters. These data reconcile several prior studies and provide both mechanical and clinical insight into cardiac iron accumulation.

Background—Transfusional therapy for thalassemia major and sickle cell disease can lead to iron deposition and damage to the heart, liver, and endocrine organs. Iron causes the MRI parameters T1, T2, and T2* to shorten in these organs, which creates a potential mechanism for iron quantification. However, because of the danger and variability of cardiac biopsy, tissue validation of cardiac iron estimates by MRI has not been performed. In this study, we demonstrate that iron produces similar T1, T2, and T2* changes in the heart and liver using a gerbil iron-overload model.Methods and Results—Twelve gerbils underwent iron dextran loading (200 mg · kg⁻¹· wk⁻¹) from 2 to 14 weeks; 5 age-matched controls were studied as well. Animals had in vivo assessment of cardiac T2* and hepatic T2 and T2* and postmortem assessment of cardiac and hepatic T1 and T2. Relaxation measurements were performed in a clinical 1.5-T magnet and a 60-MHz nuclear magnetic resonance relaxometer. Cardiac and liver iron concentrations rose linearly with administered dose. Cardiac 1/T2*, 1/T2, and 1/T1 rose linearly with cardiac iron concentration. Liver 1/T2*, 1/T2, and 1/T1 also rose linearly, proportional to hepatic iron concentration. Liver and heart calibrations were similar on a dry-weight basis.Conclusions—MRI measurements of cardiac T2 and T2* can be used to quantify cardiac iron. The similarity of liver and cardiac iron calibration curves in the gerbil suggests that extrapolation of human liver calibration curves to heart may be a rational approximation in humans.