Patterns of hepatic iron distribution in patients with chronically transfused thalassemia and sickle cell disease

Patients with sickle cell disease (SCD) appear to be at lower risk of endocrinopathies and cardiac dysfunction than those with thalassemia major (TM). Circulating redox active iron is lower in these patients, possibly due to increased systemic inflammation and circulating cytokines. Hepcidin synthesis is upregulated during chronic inflammation, reducing intestinal iron absorption and promoting retention of iron in the reticuloendothelial cells. Hence, we hypothesized that livers of patients with SCD would exhibit greater iron deposition in sinusoidal spaces relative to hepatocytes and less in portal tracts when compared to patients with TM. To test this hypothesis, iron scoring analysis was performed on 70 clinically indicated liver biopsy specimens from children and young adults with the two syndromes. Sinusoidal scores were lower in around 1 of 4 patients with TM but the relative iron loading in hepatocytes, and portal tracts was identical in both diseases. Sinusoidal iron burdens saturated at low hepatic iron concentration (HIC) while hepatocyte and portal iron depots increased proportionally to HIC. Liver fibrosis was increased in patients with TM regardless of their chronic hepatitis status. Overall, liver iron distribution was relatively insensitive to differences in disease type and to the presence or absence of hepatitis. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.     

Cardiac iron overload in sickle‐cell disease

Chronically transfused sickle cell disease (SCD) patients have lower risk of myocardial iron overload (MIO) than comparably transfused thalassemia major (TM) patients. However, cardioprotection is incomplete. We present the clinical characteristics of six patients who have prospectively developed MIO, to identify potential risk factors for cardiac iron accumulation. From 2002 to 2011, cardiac, hepatic, and pancreatic iron overload were assessed by R₂ and R₂* magnetic resonance imaging techniques in 201 chronic transfused SCD patients as part of their clinical care. At the time, they developed MIO, five of six patients had been on chronic transfusion for more than 11 years; only one was on exchange transfusion. The time to MIO was correlated with reticulocyte and hemoglobin S percentages. All patients had qualitatively poor chelation compliance (<50%). All patients had serum ferritin levels >4600 ng/ml and liver iron concentration >22 mg/g. Pancreatic R₂* was >100 Hz in every patient studied (5/6). Cardiac iron rose proportionally to pancreas R₂*, with all patients having pancreas R₂*>100 Hz when cardiac iron was present. MIO had a threshold relationship with liver iron that was higher than observed in TM patients. In conclusion, MIO occurs in a small percentage of chronically transfused SCD patients and is only associated with exceptionally poor control of total body iron stores. Duration of chronic transfusion is clearly important but other factors, such as levels of effective erythropoiesis, appear to contribute to cardiac risk. Pancreas R₂* can serve as a valuable screening tool for cardiac iron in SCD patients. Am. J. Hematol. 89:678–683, 2014. © 2014 Wiley Periodicals, Inc.     

Assessing cardiac and liver iron overload in chronically transfused patients with sickle cell disease

Transfusional iron overload represents a substantial challenge in the management of patients with sickle cell disease (SCD) who receive chronic or episodic red blood cell transfusions. Iron‐induced cardiomyopathy is a leading cause of death in other chronically transfused populations but rarely seen in SCD. Study objectives were to: (i) examine the extent of myocardial and hepatic siderosis using magnetic resonance imaging (MRI) in chronically transfused SCD patients, and (ii) evaluate the relationship between long‐term (over the 5 years prior to enrolment) mean serum ferritin (MSF), spot‐ferritin values and liver iron content (LIC) measured using MRI and liver biopsy. Thirty‐two SCD patients (median age 15 years) with transfusional iron overload were recruited from two U.S. institutions. Long‐term MSF and spot‐ferritin values significantly correlated with LIC by MRI‐R2* (r = 0·77, P < 0·001; r = 0·82, P < 0·001, respectively). LIC by MRI‐R2* had strong positive correlation with LIC by liver biopsy (r = 0·98, P < 0·001) but modest inverse correlation with cardiac MRI‐T2* (r = ?0·41, P = 0·02). Moderate to severe transfusional iron overload in SCD was not associated with aberrations in other measures of cardiac function based on echocardiogram or serum biomarkers. Our results suggest that SCD patients receiving chronic transfusions may not demonstrate significant cardiac iron loading irrespective of ferritin trends, LIC and erythropoiesis suppression.     

Evaluation of cardiac and hepatic iron overload in thalassemia major patients with T2* magnetic resonance imaging

Objectives: Recent advancements have promoted the use of T2* magnetic resonance imaging (MRI) in the non-invasive detection of iron overload in various organs for thalassemia major patients. This study aims to determine the iron load in the heart and liver of patients with thalassemia major using T2* MRI and to evaluate its correlation with serum ferritin level and iron chelation therapy.

Methods: This cross-sectional study included 162 subjects diagnosed with thalassemia major, who were classified into acceptable, mild, moderate, or severe cardiac and hepatic iron overload following their T2* MRI results, respectively, and these were correlated to their serum ferritin levels and iron chelation therapy.

Results: The study found that 85.2% of the subjects had normal cardiac iron stores. In contrast, 70.4% of the subjects had severe liver iron overload. A significant but weak correlation (r?=??0.28) was found between cardiac T2* MRI and serum ferritin, and a slightly more significant correlation (r?=?0.37) was found between liver iron concentration (LIC) and serum ferritin.

Discussion: The findings of this study are consistent with several other studies, which show that patients generally manifest with liver iron overload prior to cardiac iron overload. Moreover, iron accumulation demonstrated by T2* MRI results also show a significant correlation to serum ferritin levels.

Conclusion: This is the first study of its kind conducted in Indonesia, which supports the fact that T2* MRI is undoubtedly valuable in the early detection of cardiac and hepatic iron overload in thalassemia major patients.     

Revaluation of clinical and histological criteria for diagnosis of dysmetabolic iron overload syndrome

AIM： To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical, biochemical and histopathological findings. METHODS： We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes. The metabolic syndrome （MS） was defined according to ATPⅢ criteria. Iron overload was assessed by liver biopsy. Liver histology was evaluated by Ishak＇s score and iron accumulation by Deugnier＇s score; steatosis was diagnosed when present in ≥ 5% of hepatooltes. RESULTS： According to transferrin saturation levels, we observed significant differences in the amount of hepatic iron overload and iron distribution, as well as the number of metabolic abnormalities. Using Receiving Operating Curve analysis, we found that the presence of two components of the MS differentiated two groups with a statistically significant different hepatic iron overload （P 〈 0.0001）. Patients with ≥2 metabolic alterations and steatosis had lower amount of hepatic iron, lower transferrin saturation and higher sinusoidal iron than patients with 〈 2 MS components and absence of steatosis. CONCLUSION： In our patients, the presence of ≥ 2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation, suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation. These patients may have the typical dysmetabolic iron overload syndrome. By contrast, patients with transferrin saturation ≥ 60% had more severe iron overload, few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload.     

Hepatic iron overload in alcoholic end-stage liver disease is associated with iron deposition in other organs in the absence of HFE-1 hemochromatosis.

BACKGROUND: End-stage cirrhosis in the absence of hereditary hemochromatosis (HHC) can be associated with moderate to marked hepatic iron overload, especially in liver disease as a result of alcohol and/or hepatitis C. However, no published studies have addressed extrahepatic iron deposition in this setting. METHOD: A retrospective case series from three autopsied patients who died from end-stage cirrhosis associated with significant hepatic iron overload. Histology of vital organs was performed to detect extrahepatic iron deposition. HFE genotyping for the C282Y and H63D mutations was determined from archival tissue. Hepatic iron index and hepatic iron concentration (HIC) were quantified from formalin-fixed, paraffin-embedded tissue. Medical records were reviewed for possible causes of iron overload. RESULTS: Two patients were H63D heterozygous (H63D +/-) and one was wild type (C282Y -/-, H63D -/-). Histology revealed evidence of stainable iron in the heart and pancreas of all three subjects. Additionally, stainable iron was seen in the stomach in one subject and in the thyroid, pituitary, choroid plexus and testes in another subject. HIC ranged from 4354 to 6834 microg/g dry weight and HII from 1.8 to 2.2 (micromol/g/years). CONCLUSION: Iron overload secondary to end-stage liver disease can be associated with iron deposition in other organs in the absence of HFE-1 HHC.     

Revaluation of clinical and histological criteria for diagnosis of dysrnetabolic iron overload syndrome

AIM: To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical,biochemical and histopathological findings.METHODS: We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes.The metabolic syndrome (MS) was defined according to ATPⅢ criteria.Iron overload was assessed by liver biopsy.Liver histology was evaluated by Ishak's score and iron accumulation by Deugnier's score; steatosis was diagnosed when present in ≥ 5% of hepatocytes.RESULTS: According to transferrin saturation levels,we observed significant differences in the amount of hepatic iron overload and iron distribution,as well as the number of metabolic abnormalities.Using Receiving Operating Curve analysis,we found that the presence of two components of the MS differentiated two groups with a statistically significant different hepatic iron overload (P ＜ 0.0001).Patients with ≥ 2 metabolic alterations and steatosis had lower amount of hepatic iron,lower transferrin saturation and higher sinusoidal iron than patients with ＜ 2 MS components and absence of steatosis.CONCLUSION: In our patients,the presence of ≥2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation,suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation.These patients may have the typical dysmetabolic iron overload syndrome.By contrast,patients with transferrin saturation ≥ 60% had more severe iron overload,few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload.     

No evidence for myocardial iron overload and free iron species in multitransfused patients with sickle/β0‐thalassaemia

Iron overload (IO) in the heart is a life‐threatening complication in transfusion‐dependent patients with thalassaemia major (TM) and to a lesser extent in sickle cell disease (SCD), while no data are available in patients with sickle/β⁰‐thalassaemia. Iron deposition in the heart, liver and pancreas was assessed using T2* MRI sequences, as well as free iron species assays – non‐transferrin bound iron (NTBI) and labile plasma iron (LPI), in addition to serum ferritin, percentage transferrin saturation and serum hepcidin, in 10 multitransfused patients (>30 yr) with sickle/β⁰‐thalassaemia. None of the patients had iron deposition in the heart. Three patients had mild, one had moderate, and two had severe liver IO. Two patients had mild iron deposition in the pancreas. In all the patients, serum hepcidin levels were normal – NTBI and LPI were not detected. Possible explanations of these findings are discussed.     

Microarray analysis of liver gene expression in iron overloaded patients with sickle cell anemia and beta‐thalassemia

Chronic transfusion therapy is used clinically to supply healthy erythrocytes for patients with sickle cell anemia (SCA) or beta‐thalassemia major (TM). Despite the benefits of red blood cell transfusions, chronic transfusions lead to iron accumulation in key tissues such as the heart, liver, and endocrine glands. Transfusion‐acquired iron overload is recognized as a cause of morbidity and mortality among patients receiving chronic transfusions. At present, there is little understanding of molecular events that occur during transfusional iron loading and the reasons for the large inter‐individual variation observed clinically in transfusion‐acquired iron accumulation. To address these issues, we examined whether any liver‐expressed genes in SCA or TM patients with transfusional iron overload were associated with the degree of iron accumulation. Specifically, we performed microarray analysis on liver biopsy specimens comparing SCA patients with mild or severe iron overload and also compared SCA with TM patients. Fifteen candidate genes were identified with significantly differential expression between the high and low liver iron concentrations. SCA patients and 20 candidate genes were detected between the SCA and TM patient comparison. Subsequent quantitative PCR experiments validated 12 candidate genes; with GSTM1, eIF5a, SULF2, NTS, and HO‐1 being particularly good prospects as genes that might affect the degree of iron accumulation. Future work will determine the baseline expression of these genes prior to transfusional iron overload and elucidate the full impact of these genes on the inter‐individual variation observed clinically in transfusion‐acquired iron accumulation. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

Nontransferrin-bound iron in transfused patients with sickle cell disease

The value of nontransferrin‐bound iron (NTBI) as an index of iron overload in patients with thalassemia has been evaluated; however, data in patients with sickle cell disease (SCD) is limited. NTBI levels were evaluated in a cross‐sectional study of 43 transfused patients with SCD. Patient charts were reviewed for demographics, status of the spleen, and total number of lifetime transfusions. All patients were chelation naïve and none of the patients had evidence of hepatitis B or C infection. Blood samples were taken for assessment of NTBI and serum ferritin (SF); liver iron concentration (LIC) was determined by R2 magnetic resonance imaging. NTBI levels were generally low with a median of ?0.01 μm (range ?2.56 to 6.37 μm ). Among study variables, NTBI levels were only significantly correlated to age and total number of lifetime transfusions, whereas LIC and SF only significantly correlated with total number of lifetime transfusions. On multivariate analysis, only total number of lifetime transfusions remained independently correlated with NTBI (P = 0.001), SF (P < 0.001), and LIC (P < 0.001). On multivariate stepwise linear regression analysis, SF was a better predictor of LIC than NTBI. In transfused patients with SCD, NTBI levels are low yet correlate significantly with transfusion burden. However, they offer poor predictability of LIC when compared with SF.     

Hepatic iron and nonalcoholic fatty liver disease.

Increased iron is suspected to enhance hepatic injury associated with nonalcoholic fatty liver disease (NAFL). We evaluated the impact of iron accumulation on the outcome of NAFL. Patients with NAFL were identified from our database. Twenty-two clinicodemographic and 19 pathological features were available for each patient. Histological staining (Perls' Prussian blue), hepatic iron concentration (HIC), and hepatic iron index (HII) were determined. Data on follow-up, mortality, and cause of death were analyzed. In 65 patients with available liver biopsy blocks, HIC and HII were 1,171 +/- 717 microgram/g dry weight and 0.43 +/- 0.30 micromol/g/yr, respectively. Males had more iron accumulation (HIC: 1,514 +/- 836 vs. 859 +/- 389, P =.0001; and HII: 0.58 +/- 0.35 vs. 0.29 +/- 0.16, P =.0001). In type II diabetics, both HIC (977 +/- 769 vs. 1,301 +/- 659; P <.05) and HII (0.30 +/- 0.23 vs. 0.52 +/- 0.32; P <.05) were lower. Iron accumulation was not related to other variables analyzed. Increased iron was not seen in those with higher grades of fibrosis or other pathological features associated with the aggressive form of NAFL (hepatocyte necrosis, fibrosis, ballooning degeneration, and Mallory hyaline). Iron accumulation was not associated with increased overall mortality, liver-related mortality, or development of cirrhosis. In summary, in most patients with NAFL, significant iron accumulation is not seen. Additionally, in our series of patients with NAFL, iron is not associated with poor clinical or pathological outcomes.     

Magnetic resonance imaging in the evaluation of iron overload in patients with beta thalassaemia and sickle cell disease

Magnetic resonance imaging (MRI) appears to be useful for monitoring iron overload in thalassaemia. We studied 106 patients with beta-thalassaemia: 80 with thalassaemia major (TM) and 26 with thalassaemia intermedia (TI). Thirty-five patients with sickle cell disease (SCD) were also evaluated. Serum ferritin, liver and myocardial T2-relaxation time and liver iron concentration (LIC) were measured. LIC values, based on biopsies from 29 patients, showed a close inverse correlation with the respective liver T2-values, along with a strong positive correlation with ferritin levels in all patients. Heart T2-values correlated with left ventricular ejection fraction in TM and SCD, but not in TI patients. Both liver and heart T2-values were significantly lower in TM patients than those of TI, and SCD patients. Ferritin levels showed a strong correlation with liver T2-values in all three groups of patients. Similarly, a negative correlation was found between serum ferritin levels and heart T2-values in TM, but not in TI and SCD patients. Heart and liver T2-values showed a significant correlation only in TM patients. These results suggest that the MRI technique (T2 relaxation time) used in our study, is a reliable, safe and non-invasive method for the assessment of the deposition of iron in the liver; results for the heart become reliable only when there is heavy iron deposition.     

How we manage iron overload in sickle cell patients

Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD), but causes significant iron overload. As transfusions are used to treat the severe complications of SCD, it remains difficult to distinguish whether organ damage is a consequence of iron overload or is due to the complications treated by transfusion. Better management has resulted in increased survival, but prolonged exposure to iron puts SCD patients at greater risk for iron‐related complications that should be treated. The success of chelation therapy is dominated by patient adherence to prescribed treatment; thus, adjustment of drug regimens to increase adherence to treatment is critical. This review will discuss the current biology of iron homeostasis in patients with SCD and how this informs our clinical approach to treatment. We will present the clinical approach to treatment of iron overload at our centre using serial assessment of organ iron by magnetic resonance imaging.     

Pituitary iron and volume predict hypogonadism in transfusional iron overload

Hypogonadism is the most common morbidity in patients with transfusion‐dependent anemias such as thalassemia major. We used magnetic resonance imaging (MRI) to measure pituitary R2 (iron) and volume to determine at what age these patients develop pituitary iron overload and volume loss. We recruited 56 patients (47 with thalassemia major, five with chronically transfused thalassemia intermedia and four with Blackfan‐Diamond syndrome) to have pituitary MRIs to measure pituitary R2 and volume. Hypogonadism was defined clinically based on the timing of secondary sexual characteristics or the need for sex hormone replacement therapy. Patients with transfusional iron overload begin to develop pituitary iron overload in the first decade of life; however, clinically significant volume loss was not observed until the second decade of life. Severe pituitary iron deposition (Z > 5) and volume loss (Z < ?2.5) were independently predictive of hypogonadism. Pituitary R2 correlated significantly with serum ferritin as well as liver, pancreatic, and cardiac iron deposition by MRI. Log pancreas R2* was the best single predictor for pituitary iron, with an area under the receiving operator characteristic curve of 0.88, but log cardiac R2* and ferritin were retained on multivariate regression with a combined r² of 0.71. Pituitary iron overload and volume loss were independently predictive of hypogonadism. Many patients with moderate‐to‐severe pituitary iron overload retained normal gland volume and function, representing a potential therapeutic window. The subset of hypogonadal patients having preserved gland volumes may also explain improvements in pituitary function observed following intensive chelation therapy. Am. J. Hematol. 2011. © 2011 Wiley Periodicals, Inc.     

Chelation therapy for iron overload

Iron overload is characterized by excessive iron deposition and consequent injury and dysfunction of the heart, liver, anterior pituitary, pancreas, and joints. Because physiologic mechanisms to excrete iron are very limited, patients with iron overload and its complications need safe, effective therapy that is compatible with their coexisting medical conditions. The availability of three licensed iron chelation drugs (one parenteral, two oral) and the development and clinical investigation of other oral chelators represent new opportunities to prevent or manage iron overload in patients with heritable types of severe anemia, such as β-thalassemia major and sickle cell disease, and for the formulation of alternatives to phlebotomy therapy for patients with iron overload associated with the HFE gene and other adult age-of-onset types of hemochromatosis, African iron overload, and African-American iron overload.     

Room-temperature susceptometry predicts biopsy-determined hepatic iron in patients with elevated serum ferritin

Background. There is an ongoing clinical need for novel methods to measure hepatic iron content (HIC) noninvasively. Both magnetic resonance imaging (MRI) and superconducting quantum interference device (SQUID) methods have previously shown promise for estimation of HIC, but these methods can be expensive and are not widely available. Room-temperature susceptometry (RTS) represents an inexpensive alternative and was previously found to be strongly correlated with HIC estimated by SQUID measurements among patients with transfusional iron overload related to thalassemia. Aim. The goal of the current study was to examine the relationship between RTS and biochemical HIC measured in liver biopsy specimens in a more varied patient cohort.Material and methods. Susceptometry was performed in a diverse group of patients with hyperferritinemia due to hereditary hemochromatosis (HHC) (n = 2), secondary iron overload (n = 3), nonalcoholic fatty liver disease (NAFLD) (n = 2), and chronic viral hepatitis (n = 3) within one month of liver biopsy in the absence of iron depletion therapy.Results. The correlation coefficient between HIC estimated by susceptometry and by biochemical iron measurement in liver tissue was 0.71 (p = 0.022). Variance between liver iron measurement and susceptometry measurement was primarily related to reliance on the patient’s body-mass index (BMI) to estimate the magnetic susceptibility of tissue overlying the liver.Conclusions. We believe RTS holds promise for noninvasive measurement of HIC. Improved measurement techniques, including more accurate overlayer correction, may further improve the accuracy of liver susceptometry in patients with liver disease.     

Hepatic iron overload in blacks and whites: a comparative autopsy study

OBJECTIVE: Genetic susceptibility to iron loading is an important factor in the development of iron overload in Africans. This suggests that persons of African descent may be at risk to develop iron overload with its attendant complications, but relatively little is known about hepatic iron overload among blacks. The aim of this study was to compare the prevalence, histological features, and clinical correlates of hepatic iron overload in a group of autopsied black and white veterans. METHODS: Hepatic iron concentrations (HIC) were determined on liver tissue from autopsies performed at the John Cochran Veterans Affairs Medical Center during the period 1993 to 1996. Clinical information was obtained from autopsy protocols. Sections from livers in which the HIC exceeded the upper limit of normal were examined histologically. RESULTS: Of 256 specimens, 99 were from blacks (39%), whereas 157 were from whites (61%). Thirty-one blacks (31%) had an elevated HIC versus 44 whites (28%) (ns). In the majority of these cases (18 blacks, 30 whites), the HIC was less than twice the upper limit of normal. Nine of 15 subjects with an HIC greater than twice the upper limit of normal and no evident cause of secondary iron overload were black. CONCLUSIONS: The prevalence of mild-to-moderate hepatic iron overload was similar in this group of black and white veterans. Because of the inherent limitations of autopsy studies, prospective assessment of iron stores in healthy blacks is needed to determine more accurately the prevalence and clinical significance of iron overload in this population.     

Survival after liver transplantation in patients with hepatic iron overload: the national hemochromatosis transplant registry

BACKGROUND & AIMS: Previous uncontrolled studies have suggested that patients with hepatic iron overload have a poor outcome after liver transplantation. We examined the effect of HFE mutations on posttransplantation survival in patients with hepatic iron overload. METHODS: Two hundred sixty patients with end-stage liver disease and hepatic iron overload were enrolled from 12 liver transplantation centers. Hepatic iron concentration (HIC), hepatic iron index (HII), HFE mutation status, and survival after liver transplantation were recorded. RESULTS: HFE-associated hemochromatosis (HH) defined as homozygosity for the C282Y (n = 14, 7.2%) mutation or compound heterozygosity for the C282Y/H63D (n = 11, 5.6%) mutation was identified in 12.8% of patients. Survival postliver transplantation was significantly lower among patients with HH (1-, 3-, and 5-year survival rates of 64%, 48%, 34%, respectively) compared with simple heterozygotes (C282Y/wt or H63D/wt) or wild-type patients. Patients with HH had a hazard ratio for death of 2.6 (P = .002) after adjustment for age, United Network for Organ Sharing status, year of transplantation, and either elevated HII or HIC. Non-HH patients with hepatic iron overload also had significantly decreased survival when compared with the overall population undergoing liver transplantation (OR = 1.4, 95% CI: 1.15-1.61, P < .001). CONCLUSIONS: One- and 5-year survivals after liver transplantation are significantly lower among patients with HFE-associated HH. Our data also suggest that hepatic iron overload may be associated with decreased survival after liver transplantation, even in patients without HH. Early diagnosis of hepatic iron overload using HFE gene testing and iron depletion prior to liver transplantation may improve posttransplantation survival, particularly among patients with HH.     

Deferiprone as an oral iron chelator in sickle cell disease

Iron overload is not uncommon in sickle cell disease (SCD) and requires regular chelation therapy in several instances. The present study evaluates the effect of deferiprone in 15 adult patients with SCD (ten beta(s)/beta(0)thalassemia and five beta(s)/beta(s)) and iron overload. Deferiprone was given at a dose of 75 mg/kg daily for 12 months. The evaluation considered pre- and post-treatment values of serum ferritin, urinary iron excretion, and T2 values of liver and heart obtained by magnetic resonance imaging (MRI). Eleven patients had a liver biopsy prior to starting therapy to evaluate iron concentration (LIC). Twelve patients completed the study with satisfactory compliance. In ten of them (83.3%) the serum ferritin levels decreased significantly at the end of the trial; in eight patients (66.6%) the reduction of serum ferritin was accompanied by a significant increase of their liver T2 values. All patients had a significant increase of urinary iron excretion in response to the drug. Ferritin levels and liver T2 values correlated with liver iron concentration; on the contrary, ferritin levels and liver T2 values failed to show any correlation with heart T2 values. Heart T2 values did not also show any correlation with left ventricular ejection fraction. Deferiprone was well tolerated and did not cause any significant adverse effects. These results suggest that deferiprone may effectively decrease the iron deposition in patients with SCD; moreover, T2 MRI proves to be a reliable and rapid, noninvasive method for assessing the liver iron load in patients with SCD.     

Absence of cardiac siderosis by MRI T2* despite transfusion burden,hepatic and serum iron overload in Lebanese patients with sickle cell disease

Background: 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. Methods: 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. Results: 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. Conclusion: 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.