Evaluation of Liver Disease in a Cohort of Patients Affected by Thalassemia Intermedia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4064-4064
Author(s):  
Irene Motta ◽  
Maria Grazia Rumi ◽  
Claudia Cesaretti ◽  
Alessio Aghemo ◽  
Mirella Fraquelli ◽  
...  
Keyword(s):  
Liver Disease ◽  
Iron Overload ◽  
Cause Of Death ◽  
Iron Absorption ◽  
Iron Concentration ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Thalassemia Intermedia ◽  
Liver Iron

Abstract Abstract 4064 Poster Board III-999 Introduction Liver disease is the second cause of death for thalassemia major (TM) patients, mainly due to HCV infection and transfusional iron overload. Few data are so far available for thalassemia intermedia (TI) patients who are much less transfused but, because of chronic anemia they have an increased iron absorption. Aim the aim of this study was to evaluate the prevalence of liver disease and its progression in adult non-transfusion dependent TI patients. Patients and Methods Seventy adult TI patients (32 female/38 male, aged 42±14 years, range 22-77) regularly cared at Hereditary Anemia Center, University of Milan, were enrolled in this study in 1997 and followed for 10±1 years. Seven patients were lost and 4 died during follow-up. At enrolment (T0) 50 were splenectomized, 51 were occasionally transfused, 46 were irregularly chelated. Twenty-four (34,2%) patients were anti HCV positive of whom 13 (54,1%) were RNA positive. Results Liver transaminases were significantly different (p=0.001) among HCV-RNA positive and negative patients (ALT 59,7±32,1 vs 26,9±20,3 U/L; AST 49,1±22,8 vs 30,6±17,0 U/L respectively). Ferritin levels in the overall group were significantly higher than normal values (734±748 ng/ml). No significant difference in ferritin levels was detected among HCV-RNA positive and negative patients, while overall a correlation (r=0.687, p<0.001) between ferritin and ALT was observed. Among HCV-RNA negative patients regularly followed (49), at enrolment 12 (24,4%) had abnormal transaminases. During the follow up 12/37 (32,4%) who had normal transaminases at T0 showed abnormal values, and evaluating the overall HCV-RNA negative group abnormal transaminases were noticed in 24/49 (48,9%). Ferritin levels were increased also at the final observation (T1), but not as much as supposed to be considering the annual increased iron absorption. At T1Transient Elastography (TE), for evaluating liver fibrosis, and MRI T2*, for measuring liver iron, became available thus 42 patients had these evaluations: 9/42 had TE values >7.9 kPa (corresponding to fibrosis stage F≥2 of Metavir), and the mean value was 6,7±6,2 kPa; almost all the patients (39/42 – 92,8%) had significant high level of liver iron concentration (LIC measured through MRI T2*≥2 mg/g d.w.) with a correlation between LIC T2* and Fibroscan values (r=0.489, p=0.003). During the follow up 4 patients died: 1 for stroke and 3/4 for liver disease,(one Hepatocarcinoma (HCC) in HCV-RNA positive patient and 2 decompensated cirrhosis). Other two cases of HCC were observed, one in a patient HCV-RNA positive and 1 in an HCV-RNA negative patient; the latter having significant iron overload (LIC through MRI T2* 23,29 mg/g/dw) and a Fibroscan value diagnostic for cirrhosis (43,5 kPa). Conclusions Liver disease is the first cause of death in TI patients; 3 cases of HCC were observed in patient aged 49±1 years old of whom 1 without hepatitis viral infection. The liver damage, detected with high levels of ALT and AST in both HCV-RNA positive and negative patients is mainly related to the parenchymal iron overload and HCV infection. Ferritin, commonly used to monitor iron overload, properly reflects the degree of iron concentration in TM, while is inadequate in TI patients because, even though it correlates with LIC, it underestimates the iron overload. Actually in TI patients iron coming from duodenal absorption is mainly stored in parenchymal liver tissue, while in TM it's primarily distributed in the reticulo-endothelial system that stimulate ferritin production. In conclusion it's mandatory the use of other methods to evaluate LIC, such as MRI T2*, and the introduction of regular chelation therapy in the management of TI patients. Disclosures: No relevant conflicts of interest to declare.

Correlation of Serum Ferritin Levels and Liver Iron Concentration Determined by R2* MRI in Patients with Thalassemia Intermedia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3818-3818
Author(s):  
Ali Taher ◽  
F. El Rassi ◽  
H. Ismaeel ◽  
S. Koussa ◽  
A. Inati
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Care Center ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Thalassemia Intermedia ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Cross Sectional ◽  
Transfusion Therapy

Abstract Background: Unlike patients with thalassemia major (TM), those with thalassemia intermedia (TI) do not require regular blood transfusion therapy but remain susceptible to iron overload due to increased intestinal iron uptake triggered by ineffective erythropoiesis. TI patients can accumulate 1–3.5 g of excess iron per year, and effective monitoring of iron burden is an important element of patient management. Assessment of serum ferritin (SF) levels is a convenient and widely used method, and a correlation between SF and liver iron concentration (LIC) has been demonstrated in patients with TM. SF levels may, however, be a poor indicator of LIC in patients with TI and the limited data available on the SF:LIC correlation prove equivocal; in fact, reports suggest a discrepancy between LIC and SF in patients with TI. This is the largest study to use R2* MRI to evaluate the SF:LIC correlation in patients with TI. Methods: This was a cross-sectional study of randomly selected, infrequently/non-transfused TI patients treated at a chronic care center in Hazmieh, Lebanon. Patient charts were reviewed and a medical history was compiled. Blood samples were taken for SF assessment, and LIC was determined by R2* MRI. Results: Data from 74 TI patients were included in this analysis (33 male, 41 female; mean age 26.5 ± 11.5 years). Of this group, 59 (79.7%) patients were splenectomized, 20 were transfusion-naive, 45 had received several transfusions in their lifetime but none in the past year, and 9 patients were regularly transfused 2–4 times per year. Overall mean SF values were 1023 ± 780 ng/mL (range 15–4140); mean LIC levels were 9.0 ± 7.4 mg Fe/g dry weight [dw] (range 0.5–32.1). In contrast to previous findings, a significant positive correlation between mean LIC and SF values was seen in the whole group (R=0.64; P&lt;0.001), and in a subset of splenectomized patients (R=0.62; P&lt;0.001). In comparison with data obtained from a randomly selected group of patients with TM treated at the center, SF levels in TI were seen to be significantly lower, while the mean LIC values were similar in both groups of TI and TM. For a given LIC, SF values were lower in patients with TI than those with TM (Figure). Conclusions: Evaluation of iron levels shows that many patients with TI have SF and LIC levels above the recommended threshold levels, indicating a risk of significant morbidity/mortality. Similar to TM, a significant correlation between SF and LIC was observed in patients with TI; however, the relationship between SF and LIC was different between TI and TM (for the same LIC, the SF values in TI were lower than those in TM). Therefore, use of the current threshold for iron overload based on SF values in TM will lead to significant underestimation of the severity of iron overload in patients with TI. This may result in delayed chelation therapy, and expose patients to morbidity and mortality risks associated with iron overload. Disease-specific management approaches are therefore required in patients with TI. This includes either regular assessments of LIC, ideally by non-invasive R2* MRI, or lowering the SF threshold for initiating iron chelation in patients with TI. Figure Figure

ß-Thalassemic Mice Require Functional Hfe to Modulate Hepcidin Expression In Response to Iron Overload

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2063-2063
Author(s):  
Pedro Ramos ◽  
Sara Gardenghi ◽  
Robert W Grady ◽  
Maria de Sousa ◽  
Stefano Rivella
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Dry Weight ◽  
Thalassemia Intermedia ◽  
Liver Iron Concentration ◽  
Ineffective Erythropoiesis ◽  
Liver Iron ◽  
Hepcidin Expression ◽  
Smad Protein ◽  
Over Time

Abstract Abstract 2063 ß-Thalassemia is a genetic disorder characterized by decreased or absent production of ß-globin chains, leading to ineffective erythropoiesis, anemia and iron overload. Hepcidin, the hormone that controls iron homeostasis, is regulated by several mechanisms, including erythropoiesis, iron overload, inflammation and hypoxia. In the absence of transfusion therapy, patients with ß-thalassemia major exhibit a severe ineffective erythropoiesis that suppresses hepcidin expression. However, in patients or animal affected by ß-thalassemia intermedia (th3/+), iron overload is associated with a milder form of ineffective erythropoiesis. In this study we investigated whether th3/+ mice retain the ability to modulate hepcidin expression in response to iron load, despite their increased erythropoietic activity. We analyzed some of the genes involved in the regulation of hepcidin, in particular, genes that are upregulated by iron overload in wt mice. These included Bmp6, a strong modulator of Hamp in response to iron, and Id1, Atoh8 and Smad7, other targets of the Bmp/Smad pathway. Analysis of the phosphorylation of the Smad protein complex is in progress. In addition, we generated mice affected by ß-thalassemia intermedia lacking the Hfe gene (Hfe-th3/+), in an attempt to determine whether or not this gene is involved in hepcidin regulation in this disorder. We analyzed th3/+ mice at 2, 5 and 12 months of age. In 2-month-old th3/+ mice hepcidin expression was significantly low compared to wt mice. As th3/+ mice age and their iron overload worsens, hepcidin expression increases showing similar and elevated levels in th3/+ compared to wt animals, respectively at 5 and 12 months. At 2 months, hepcidin expression normalized to liver iron concentration exhibited even lower levels in th3/+ mice compared to wt animals. This ratio did not change in aging th3/+ animals, despite the fact that their liver iron concentration increased over time (0.66, 1.24, and 1.45 ug/mg of dry weight at 2, 5 and 12 months, respectively). The expression levels of Bmp6, Id1, Atoh8 and Smad7 followed a similar pattern, being generally downregulated at 2 months compared to wt mice. However, as iron overload progressed, th3/+ mice exhibited increased expression of these genes compared to wt mice. Similar to what was observed with hepcidin, their expression was low in th3/+ mice at all ages when normalized to liver iron concentration. These observations indicate that hepcidin expression in ß-thalassemia increases over time and is regulated by the relative levels of ineffective erythropoiesis and iron overload. We also investigated the relationship between Hfe and hepcidin in response to iron in ß-thalassemia. We transplanted the ß-thalassemic phenotype into lethally irradiated wt or Hfe-KO mice, generating th3/+ and Hfe-th3/+ animals, respectively. Compared to th3/+ mice, we observed that Hfe-th3/+ animals had increased hepatic iron (3.09 vs 1.29 ug/mg of dry weight, p≤0.05) and serum iron (232 vs 162 ug/dL, p≤0.05), with no significant changes in splenic iron concentration. The Hfe-th3/+ mice also exhibited increased hemoglobin levels (9.4 vs 7.8 g/dL, p≤0.001) due to an increase in both red cell counts (8.9 vs 8.0 ×106 cells/uL, p≤0.01) and mean corpuscular hemoglobin levels (10.6 vs 9.7 pg, **p≤0.05). However, this did not reduce splenomegaly or ineffective erythropoiesis. We also analyzed the levels of hepcidin, Bmp6, Id1, Smad7 and Atoh8 in 5-month-old mice. At his time point expression of most of these genes was similar between wt, th3/+ and Hfe-th3/+ mice. Only expression of Bmp6 was elevated in the two thalassemic groups compared to wt mice. When the levels of hepcidin, Bmp6, Id1, Smad7 and Atoh8 expression were normalized to liver iron content, we observed significant reductions in Hfe-th3/+ mice compared to th3/+ animals. Taken together, these observations indicate that iron overload can partially counteract the repressive effect of ineffective erythropoiesis on hepcidin expression in th3/+ mice. Moreover, lack of Hfe further impairs the ability of hepcidin and other iron regulated genes to respond to iron overload, aggravating this feature in thalassemic mice. Overall, this indicates that Hfe plays a positive role in the regulation of hepcidin in ß-thalassemia. Disclosures: No relevant conflicts of interest to declare.

Longitudinal Follow-up From Newborn Screening Reveals Deletional Hemoglobin H Disease and Hemoglobin H Constant Spring Disease Are Distinct Thalassemia Syndromes

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4260-4260
Author(s):  
Ashutosh Lal ◽  
Michael Lee Goldrich ◽  
Drucilla Foote ◽  
Mahin Azimi ◽  
Sylvia Titi Singer ◽  
...  
Keyword(s):  
Iron Overload ◽  
Newborn Screening ◽  
Serum Ferritin ◽  
Iron Concentration ◽  
Growth Failure ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
The Mean ◽  
Hemoglobin H Disease

Abstract Abstract 4260 Background: Alpha thalassemia disorders are rapidly increasing in North America. This has resulted in proposals for universal newborn screening (NBS) for hemoglobin H disease. However, the institution of routine newborn screening and construction of guidelines for early intervention requires longitudinal clinical data before setting national goals. Since 1995, California has performed universal screening for alpha thalassemia disorders. The longitudinal follow up of data from patients with hemoglobin H disorders diagnosed in the asymptomatic period provides essential information needed for formulating public health policy. Methods: Hemoglobin H disorders were diagnosed by high performance liquid chromatography with multiplex GAP-PCR assay to determine deletional hemoglobin H disease (deletion of 3 α globin genes, HbH) and the non-deletional hemoglobin H Constant Spring (α0 thalassemia with Constant Spring mutation, HCS). Longitudinal clinical data for all patients from the Northern California Thalassemia Center were analyzed. Ethnicity, growth data, clinic visits, hospitalizations, complications including splenectomy, transfusion, and iron overload were monitored. Quantitative liver iron concentration was determined by ferritometer. Results: 86 patients predominantly diagnosed through NBS were longitudinally followed. Out of these, 60 (70%) had HbH, 23 (27%) had HCS and 3 (3%) had other forms of hemoglobin H disease. The parental ethnicity in HbH was 79% Asian, 6% Hispanic, and 15% African-American (in one or both parents). All patients with HCS were of Asian ethnicity. Longitudinal data for hemoglobin revealed that anemia was more severe in HCS at all ages (p<0.001). Mean hemoglobin in HbH increased from 8.8 g/dL (6.9-10.6 g/dL) at 6 months to 9.4 g/dL (7.9-11.5 g/dL) at 5 years (p<0.001). However, mean hemoglobin in HCS remained unchanged from 7.4 g/dL (5.8-9.9 g/dL) at 6 months to 7.2 g/dL (3.8-8.7 g/dL) at 5 years (p=ns). There was no hemoglobin value <6.7 g/dL in 237 patient-years of observation of 60 patients with HbH. Compared to HbH, red blood cells in HCS had higher mean corpuscular hemoglobin (18.6 versus 16.6 pg, p<0.001) and mean corpuscular volume (65.2 versus 54.0 fL, p<0.001). The mean absolute reticulocyte count was 88.2 ×103/μL in HbH versus 235.1 ×103/μL in HCS (p<0.001), while the mean serum bilirubin was 0.56 mg/dL and 2.60 mg/dL, respectively (p<0.001). Clinical severity and complications were markedly worse in HCS in contrast with HbH. Growth was delayed in HCS with mean weight-for-age Z-score -0.91 compared with -0.06 in HbH (p<0.001). The mean height-for-age Z-score was also lower in HCS (-1.29) compared with HbH (-0.43, p<0.001). The striking susceptibility to acute worsening of anemia with infections requiring urgent blood transfusion was observed in HCS, but not in HbH. The probability of receiving one or more blood transfusion by 20 years was 3% in HbH and 82% in HCS (p<0.001). Transfusions in HCS were required for 13% infants and median transfusion-free survival was 6 years. Splenectomy improved hemoglobin by 2.9 g/dL (0.4 to 4.0 g/dL, p=0.012) and reduced transfusions in HCS. Iron overload, measured by serum ferritin and liver iron concentration, developed during the first decade in HCS and increased during follow up. Median ferritin in HCS between 12 –17 years was 330 ng/mL (66-1420 ng/mL). Serum ferritin in HbH did not increase between 0–18 years (median 40 ng/mL, range 5–182 ng/mL), but older patients showed strong positive correlation between age and ferritin (p<0.001). In patients with HbH or HCS undergoing ferritometer examination, the degree of serum ferritin elevation underestimated the liver iron concentration. Conclusions: Our data support the utility of a universal NBS program, particularly in areas where αCS mutation is prevalent, since young infants with HCS can develop life-threatening anemia. HCS is a serious disease that needs close follow-up by a specialty thalassemia center to plan for emergency and elective transfusions, measure iron overload, monitor growth failure and evaluate the need for splenectomy. In contrast, HbH is asymptomatic during infancy and childhood; its complications are age-dependent, and monitoring for hemosiderosis and growth failure is more important in older children. In summary, HCS should be recognized as a thalassemia syndrome distinct from HbH with a different screening and treatment approach. Disclosures: No relevant conflicts of interest to declare.

A MRI Prospective Survey on Heart and Liver Iron and Cardiac Function in Thalassemia Major Patients Treated with Deferasirox Versus Deferiprone and Desferrioxamine in Monotherapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3631-3631
Author(s):  
Alessia Pepe ◽  
Laura Pistoia ◽  
Liana Cuccia ◽  
Monica Fortini ◽  
Vincenzo Caruso ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Myocardial Iron ◽  
Liver Iron ◽  
Biventricular Function

Abstract Background: No prospective data are available about the efficacy of deferasirox versus deferiprone and desferrioxamine in monotherapy. Our study aimed to prospectively assess the efficacy of deferasirox versus deferiprone and desferrioxamine in monotherapy in a large cohort of thalassemia major (TM) patients by quantitative Magnetic Resonance (MR). Methods: Among the 2551 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we selected those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans. We identified three groups of patients: 235 treated with DFX, 142 with DFP and 162 with DFO. Iron overload was measured by T2* multiecho technique. Liver T2* values were converted into liver iron concentration (LIC) values. Biventricular function parameters were quantitatively evaluated by cine images. Results: Excellent/good levels of compliance were similar in the DFX (98.7%) vs DFP (96.3%) and DFO (97.5%) groups. Among the patients with myocardial iron overload at baseline, in all three groups there was a significant improvement in the global heart T2* value (DFX: +4.58±5.91ms P<0.0001, DFP: 8.53±6.97ms P<0.0001 and DFO: +3.93±5.21 ms P<0.0001) and a reduction in the number of pathological segments (DFX: -4.49±4.55 P<0.0001, DFP: -8.08±5.5.84 ms P=0.001 and DFO: -3.65±3.81 ms P<0.0001). In DFP and in DFO groups there was a significant improvement in left ventricular ejection function (LVEF) (+4.86±6.99% P=0.044 and +3.87±7.48% P=0.004, respectively). Only in the DFP group there was a significant improvement in right ventricular ejection function (RVEF) (6.69±4.61% P=0.001). The improvement in the global heart T2* was significantly lower in the DFX versus the DFP group , but it was not significantly different in the DFX versus the DFO group (Figure 1). The improvement in the LVEF was significantly higher in both DFP and DFO groups than in the DFX group while the improvement in the RVEF was significantly higher in the DFP than in DFX group (Figure 2). Among the patients with hepatic iron at baseline (LIC≥3mg/g dw) the changes were not significantly different in DFX versus the other groups. Conclusions: Prospectively in a large clinical setting of TM patients, DFX monotherapy was significantly less effective than DFP in improving myocardial siderosis and biventricular function and it was significantly less effective than DFO in improving the LVEF. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc..

Association Between Cardiac Iron Clereance and Hepatic Siderosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4833-4833
Author(s):  
Alessia Pepe ◽  
Laura Pistoia ◽  
Domenico D'Ascola ◽  
Maria Rita Gamberini ◽  
Francesco Gagliardotto ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Hepatic Iron ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Follow Up Study ◽  
Hepatic Iron Overload

Abstract Introduction. The aim of this multicenter study was to evaluate in thalassemia major (TM) if the cardiac efficacy of the three iron chelators in monotherapy was influenced by hepatic iron levels over a follow up of 18 months. Methods. Among the 2551 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we evaluated prospectively the 98 patients those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans and who showed evidence of significant cardiac iron (global heart T2*<20 ms) at the basal MRI. Iron overload (IO) was measured by T2* multiecho technique. We used cardiac R2* (equal to 1000/T2*) because cardiac R2* is linearly proportional to cardiac iron and hepatic T2* values were converted into liver iron concentration (LIC) values. Results. We identified 3 groups of patients: 47 treated with deferasirox (DFX), 11 treated with deferiprone (DFP) and 40 treated with desferrioxamine (DFO). Percentage changes in cardiac R2* values correlated with changes in LIC in both DFX (R=0.469; P=0.001) and DFP (R=0.775; P=0.007) groups. All patients in these 2 groups who lowered their LIC by more than 50% improved their cardiac iron (see Figure 1). Percentage changes in cardiac R2* were linearly associated to the log of final LIC values in both DFX (R=0.437; P=0.002) and DFP groups (R=0.909; P<0.0001). Percentage changes in cardiac R2* were not predicted by initial cardiac R2* and LIC values. In each chelation group patients were divided in subgroups according to the severity of baseline hepatic iron overload (no, mild, moderate, and severe IO). The changes in cardiac R2* were comparable among subgroups (P=NS) (Figure 2). Conclusion. In patients treated with DFX and DFP percentage changes in cardiac R2* over 18 months were associated with final LIC and percentage LIC changes. In each chelation group percentage changes in cardiac R2* were no influenced by initial LIC or initial cardiac R2*. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc..

scholarly journals A T2* MRI Prospective Survey on Cardiac and Hepatic Iron in Non-Trasfusion-Dependent Thalassemia Intermedia Patients Treated with Desferrioxamine

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4900-4900
Author(s):  
Antonella Meloni ◽  
Aurelio Maggio ◽  
Carlo Cosmi ◽  
Alfonso D'Ambrosio ◽  
Elena Facchini ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Real Life ◽  
Hepatic Iron ◽  
Thalassemia Intermedia ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Hepatic Iron Overload ◽  
Cardiac Iron Overload

Abstract Background. In thalassemia intermedia (TI) patients no observational study prospectively evaluated in the real life the efficacy of the desferrioxamine (DFO) therapy in removing or preventing iron overload from the heart and the liver by T2* Magnetic Resonance Imaging (MRI). The efficacy endpoint of this study is represented by the changes in cardiac T2* and MRI LIC (liver iron concentration) values in non-transfusion dependent (NTD) TI patients after 18 months of desferrioxamine therapy. Methods. Among the 325 TI patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we selected 129 TI patients NTD. We considered 29 patients who had been received DFO alone between the two MRI scans. Cardiac iron overload was assessed by the T2* multiecho technique. Hepatic T2* values were converted into liver iron concentration (LIC) values. Results. Mean age was 39.69 ± 8.12 years and 14 (48.3%) patients were females. Patients started regular chelation therapy at a mean age of 21.92 ± 15.89 years. The mean administered dosage of DFO via subcutaneous route was 38.46 ± 10.27 mg/kg body weight on 3.32 ± 1.54 days/week. The percentage of patients with excellent/good levels of compliance to the chelation treatment was 82.1%. At baseline only one patient showed cardiac iron overload (global heart T2*=15.23 ms) but he recovered at the FU (global heart T2*=26.93 ms). All patients without cardiac iron maintained the same status at the follow-up (FU). Eighteen patients (62.1%) had hepatic iron overload (MRI LIC ≥3 mg/g/dw) at the baseline. For this subgroup, the baseline and the FU LIC values were, respectively, 9.15 ± 7.97 mg/g/dw and 7.41 ± 6.28 mg/g/dw. The reduction in MRI LIC values was not significant (P=0.102). Out of the 11 patients with a baseline MRI LIC <3 mg/g/dw, only one (9.1%) showed hepatic iron at the FU. The Figure shows the evolution of different hepatic iron overload risk classes between the baseline and the FU. Conclusions. In this small population of sporadically or non transfused TI patients, DFO showed 100% efficacy in maintaining a normal global heart T2* value. As regards as the hepatic iron overload, the DFO therapy did not prevent the transition to a worst class in 2 patients. Figure 1 Figure 1. Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.

scholarly journals Histological Scores Validate the Accuracy of Hepatic Iron Load Measured by Signal Intensity Ratio and R2* Relaxometry MRI in Dialysis Patients

2019 ◽  
Vol 9 (1) ◽  
pp. 17 ◽  
Author(s):  
Guy Rostoker ◽  
Mireille Laroudie ◽  
Raphaël Blanc ◽  
Mireille Griuncelli ◽  
Christelle Loridon ◽  
...  
Keyword(s):  
Iron Overload ◽  
Signal Intensity ◽  
Intensity Ratio ◽  
Iron Concentration ◽  
Positive Likelihood Ratio ◽  
Quantitative Mri ◽  
Signal Intensity Ratio ◽  
Dialysis Patients ◽  
Liver Iron

Almost all haemodialysis patients are treated with parenteral iron to compensate for blood loss and to allow the full therapeutic effect of erythropoiesis-stimulating agents. Iron overload is an increasingly recognised clinical situation diagnosed by quantitative magnetic resonance imaging (MRI). MRI methods have not been fully validated in dialysis patients. We compared Deugnier’s and Turlin’s histological scoring of iron overload and Scheuer’s classification (with Perls’ stain) with three quantitative MRI methods for measuring liver iron concentration (LIC)—signal intensity ratio (SIR), R2* relaxometry, and R2* multi-peak spectral modelling (Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL-IQ®)) relaxometry—in 16 haemodialysis patients in whom a liver biopsy was formally indicated for medical follow-up. LIC MRI with these three different methods was highly correlated with Deugnier’s and Turlin’s histological scoring (SIR: r = 0.8329, p = 0.0002; R2* relaxometry: r = −0.9099, p < 0.0001; R2* relaxometry (IDEAL-IQ®): r = −0.872, p = 0.0018). Scheuer’s classification was also significantly correlated with these three MRI techniques. The positive likelihood ratio for the diagnosis of abnormal LIC by Deugnier’s histological scoring was > 62 for the three MRI methods. This study supports the accuracy of quantitative MRI methods for the non-invasive diagnosis and follow-up of iron overload in haemodialysis patients.

Lack of Correlation between Serum Ferritin and Liver Iron Concentration in Beta-Zero Thalassemia Intermedia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3620-3620 ◽  
Author(s):  
Renzo Galanello ◽  
Nicolina Giagu ◽  
Susanna Barella ◽  
Liliana Maccioni ◽  
Raffaella Origa
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Regulatory Protein ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Dry Weight ◽  
Thalassemia Major ◽  
Thalassemia Intermedia ◽  
Liver Iron Concentration ◽  
Liver Iron

Abstract Serum ferritin and liver iron concentration (LIC) are the most commonly used methods for assessment of iron overload in thalassemia. While in patients with thalassemia major a significant correlation has been found between these two parameters, data are lacking in patients with thalassemia intermedia. In this study we measured the serum ferritin and LIC in 22 adult patients with beta-zero thalassemia intermedia never transfused (14 patients) or sporadically transfused, i.e. less than 10 units in total (8 patients), who maintained a mean hemoglobin of 8.8 ± 1.1 g/dl. Serum ferritin levels were measured by an automated chemiluminescence immunoassay analyzer, whereas LIC was determined by atomic absorption in liver biopsies. We compared the results obtained in those patients with those obtained in 22 regularly transfused (mean annual Hb = 11.3 ± 0.3 g/dl) and iron chelated thalassemia major patients, matched by sex, age and liver iron concentration. We also determined serum erythropoietin (s-epo) and serum transferrin receptor (s-TfR) in a cohort of the two patient groups (12 thalassemia intermedia; 15 thalassemia major). Mean LIC was 11.3 ± 6 mg/g dry weight tissue in thalassemia intermedia, and 11.8 ± 7 mg/g d.w. in thalassemia major group. Mean serum ferritin (at least 2 determinations from each patient within ± 2 months of liver biopsy) was 627 ± 309 ng/ml in thalassemia intermedia and 2748 ± 2510 ng/ml in thalassemia major. The difference was statistically significant (p = 0.0001). LIC was weakly correlated with serum ferritin in thalassemia major patients (r2=0.46; p=0.001) and uncorrelated in patients with thalassemia intermedia (r2=0.04; p=0.37) (Figure). S-epo and s-TfR were significantly higher in thalassemia intermedia than in thalassemia major [s-epo 467 ± 454 mU/ml versus 71 ± 44 mU/ml (p<0.001); s-TfR 43 ± 13 mU/ ml versus 13 ± 6 mU/ml (p<0.0001)]. The discrepancy between LIC and serum ferritin in thalassemia intermedia patients may be due to the higher levels of s-epo (secondary to anemia) in those patients, which through the iron regulatory protein 1 determine an up-regulation of s-TfR and a repression of ferritin translation (Weiss et al 1997). The mechanism of iron overload may also be mediated by hepcidin, whose synthesis could be suppressed as a consequence of anemia. The observation reported has important implications for iron chelation in patients with thalassemia intermedia. In such patients serum ferritin levels have little value for the monitoring of iron overload. Figure Figure

MRI Prospective Survey on Cardiac and Hepatic Iron in Thalassemia Intermedia Patients Treated with Desferrioxamine, Deferiprone and Deferasirox

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4041-4041
Author(s):  
Antonella Meloni ◽  
Aurelio Maggio ◽  
Anna Pietrapertosa ◽  
Pier Paolo Bitti ◽  
Sabrina Armari ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Hepatic Iron ◽  
Thalassemia Intermedia ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Number Of Patients ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri

Abstract Background. Few studies have evaluated the efficacy of iron chelation therapy in thalassemia intermedia (TI) patients. Our study aimed to prospectively assess by quantitative Magnetic Resonance imaging (MRI) the efficacy of the three available chelators in monotherapy in transfusion dependent (TD) TI patients. Methods. Among the 325 TI patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we selected 103 TI patients TD with an MRI follow-up (FU) study at 18±3 months who had been received one chelator alone between the two MRI scans. Iron overload was assessed by the T2* multiecho technique. Hepatic T2* values were converted into liver iron concentration (LIC) values. Results. Three groups of patients were identified: 27 patients (13 females, mean age 40.12±10.31 years) treated with desferioxamine (DFO – mean dosage 37.52±8.69 mg/kg/die), 23 patients (14 females, mean age 34.73±10.67 years) treated with deferiprone (DFP– dosage 71.70±14.46mg/kg/die) and 14 patients (9 females, mean age 36.63±10.92 years) treated with deferasirox (DFX – mean dosage 27.75±5.04 mg/kg/die). Excellent/good levels of compliance were similar in the DFO (92.6%), DFP (100%) and DFX (100%) groups (P=0.345). The mean starting age of regular transfusion was 14.73±15.89 years. At baseline in DFO group two patients (7.4%) showed a global heart T2*<20 ms and one of them showed no cardiac iron at the FU. At baseline in DFP group two patients (8.7%) showed a global heart T2*<20 ms and one of them showed no cardiac iron at the FU. All the 5 patients (35.7%) under DFX therapy with pathological global heart T2* at the baseline remained at the same status at the FU. The percentage of patients who maintained a normal global heart T2* value was comparable for DFO (100%), DFP (100%) and DFX (88.9%) groups (P=0.164). Among the 46 patients with hepatic iron at baseline (MRI LIC ≥3 mg/g/dw), the reduction in the MRI LIC values was significant only in the DFO group (DFO: -3.39±6.38 mg/g/dw P=0.041; DFP: -2.25±6.01 mg/g/dw P=0.136 and DFX: -0.36±5.56 mg/g/dw P=0.875). The decrease in MRI LIC values was comparable among the groups (P=0.336). The number of patients with a MRI LIC<3 mg/g/dw went up from 10 (37%) to 11 (40.7%) in the DFO group, from 6 (26.1%) to 8 (34.8%) in the DFP group and from 2 (14.3%) to 8 (57.1%) in the DFX group. The percentage of patients who maintained a normal MRI LIC value was comparable for DFO (90%) vs DFP (50%) and DFX (100%) groups (P=0.191). Conclusion: Prospectively in transfusion-dependent TI patients at the dosages used in the clinical practice, DFO and DFP showed 100% efficacy in maintaining a normal global heart T2* value while DFX had 100% efficacy in maintaining a normal LIC value. Further prospective studies involving more patients with iron at the baseline are needed to establish which is the most effective drug in reducing iron levels. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc.: Speakers Bureau; Novartis: Speakers Bureau.

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