RESUMO
BACKGROUND: In transfusion-dependent thalassemia patients who started regular transfusions in early childhood, we prospectively and longitudinally evaluated the efficacy on pancreatic iron of a combined deferiprone (DFP) + desferrioxamine (DFO) regimen versus either oral iron chelator as monotherapy over a follow-up of 18 months. MATERIALS AND METHODS: We selected patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network who received a combined regimen of DFO+DFP (No.=28) or DFP (No.=61) or deferasirox (DFX) (No.=159) monotherapy between the two magnetic resonance imaging scans. Pancreatic iron overload was quantified by the T2* technique. RESULTS: At baseline no patient in the combined treatment group had a normal global pancreas T2* (≥26 ms). At follow-up the percentage of patients who maintained a normal pancreas T2* was comparable between the DFP and DFX groups (57.1 vs 70%; p=0.517).Among the patients with pancreatic iron overload at baseline, global pancreatic T2* values were significantly lower in the combined DFO+DFP group than in the DFP or DFX groups. Since changes in global pancreas T2* values were negatively correlated with baseline pancreas T2* values, the percent changes in global pancreas T2* values, normalized for the baseline values, were considered. The percent changes in global pancreas T2* values were significantly higher in the combined DFO+DFP group than in either the DFP (p=0.036) or DFX (p=0.030) groups. DISCUSSION: In transfusion-dependent patients who started regular transfusions in early childhood, combined DFP+DFO was significantly more effective in reducing pancreatic iron than was either DFP or DFX.
Assuntos
Sobrecarga de Ferro , Talassemia , Talassemia beta , Humanos , Pré-Escolar , Ferro/uso terapêutico , Deferasirox , Deferiprona/uso terapêutico , Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Piridonas/uso terapêutico , Talassemia beta/diagnóstico por imagem , Talassemia beta/tratamento farmacológico , Benzoatos/uso terapêutico , Triazóis/uso terapêutico , Quimioterapia Combinada , Sobrecarga de Ferro/diagnóstico por imagem , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Pâncreas/diagnóstico por imagemRESUMO
We assessed the value of pancreatic T2* magnetic resonance imaging (MRI) for predicting cardiac events from a large prospective database of transfusion-dependent thalassemia (TDT) patients. We considered 813 TDT patients (36.47 ± 10.71 years, 54.6% females) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. MRI was used to measure hepatic, pancreatic, and cardiac iron overload (IO), to assess biventricular function and atrial dimensions, and to detect replacement myocardial fibrosis. The mean follow-up was 50.51 ± 19.75 months. Cardiac complications were recorded in 21 (2.6%) patients: one with heart failure (HF) and 20 with arrhythmias. The single patient who developed HF had, at the baseline MRI, a reduced pancreas T2*. Out of the 20 recorded arrhythmias, 17 were supraventricular. Pancreatic T2* values were a significant predictor of future arrhythmia-related events (hazard ratio = 0.89; p = 0.015). Pancreas T2* remained significantly associated with future arrhythmias after adjusting for any other univariate predictor (age and male sex, diabetes, history of previous arrhythmias, or left atrial area index). According to the receiver-operating characteristic curve analysis for arrhythmias, a pancreas T2* < 6.73 ms was the optimal cut-off value. In TDT, pancreatic iron levels had significant prognostic power for arrhythmias. Regular monitoring and the development of targeted interventions to manage pancreatic IO may help improve patient outcomes.
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BACKGROUND: The E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) project is an Italian Network assuring high-quality quantification of tissue iron overload by magnetic resonance imaging (MRI). We evaluated the impact of the COVID-19 pandemic on E-MIOT services. METHODS: The activity of the E-MIOT Network MRI centers in the year 2020 was compared with that of 2019. A survey evaluated whether the availability of MRI slots for patients with hemoglobinopathies was reduced and why. RESULTS: The total number of MRI scans was 656 in 2019 and 350 in 2020, with an overall decline of 46.4% (first MRI: 71.7%, follow-up MRI: 36.9%), a marked decline (86.9%) in the period March-June 2020, and a reduction in the gap between the two years in the period July-September. A new drop (41.4%) was recorded in the period October-December for two centers, due to the general reduction in the total amount of MRIs/day for sanitization procedures. In some centers, patients refused MRI scans for fear of getting COVID. Drops in the MRI services >80% were found for patients coming from a region without an active MRI site. CONCLUSIONS: The COVID-19 pandemic had a strong negative impact on MRI multi-organ iron quantification, with a worsening in the management of patients with hemoglobinopathies.
Assuntos
COVID-19 , Hemoglobinopatias , Sobrecarga de Ferro , Humanos , COVID-19/diagnóstico por imagem , Pandemias , Hemoglobinopatias/complicações , Hemoglobinopatias/diagnóstico por imagem , Sobrecarga de Ferro/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: No study has evaluated the effect of hepatitis C virus (HCV) infection on the wide spectrum of complications affecting patients with thalassemia. OBJECTIVES: This multicenter study prospectively assessed the relationship of HCV infection with diabetes mellitus and cardiovascular complications in patients with thalassemia major (TM). METHODS: We considered 1057 TM patients (539 females; 29.79±10.08 years) enrolled in the MIOT Network and categorized into 4 groups: negative patients (group 1a, N=460), patients who spontaneously cleared the virus within 6months (group 1b, N=242), patients who eradicated the virus after the treatment with antiviral therapy (group 2, N=102), and patients with chronic HCV infection (group 3, N=254). RESULTS: Group 1a and 1b were considered as a unique group (group 1). For both groups 1 and 3, a match 1:1 for age and sex with group 2 was performed. The effective study cohort consisted of 306 patients (three groups of 102 patients). During a mean follow-up of 67.93±39.20months, the group 3 experienced a significantly higher % increase/month in aspartate transaminase levels and left ventricular mass index than both groups 1 and 2. The changes in iron overload indexes were comparable among the three groups. Compared to group 1, the chronic HCV group showed a significantly higher risk of diabetes (hazard ratio-HR=5.33; p=0.043) and of cardiovascular diseases (HR=3.80; p=0.034). CONCLUSION: Chronic HCV infection is associated with a significant higher risk of diabetes mellitus and cardiovascular complications in TM patients and should be approached as a systemic disease in which extrahepatic complications increase the weight of its pathological burden.
Assuntos
Diabetes Mellitus , Cardiopatias , Hepatite C Crônica , Hepatite C , Talassemia , Talassemia beta , Feminino , Humanos , Talassemia beta/complicações , Talassemia beta/epidemiologia , Hepatite C/complicações , Talassemia/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Hepacivirus , Diabetes Mellitus/epidemiologia , MorbidadeRESUMO
We report data on survival and complications for a longitudinal cohort of 709 transfusion-dependent ß-thalassemia major patients (51.1% males) born between 1970 and 1997 and followed through 2020 at seven major centers in Italy. Overall survival probability at 30 years was 83.6% (95%CI: 78.5-89.1) in the oldest birth cohort (1970-1974) compared with 93.3% (95%CI: 88.6-98.3) in the youngest birth cohort (1985-1997) (p = 0.073). Females showed better survival than males (p = 0.022). There were a total of 93 deaths at a median age of 23.2 years with the most frequent disease-related causes being heart disease (n = 53), bone marrow transplant (BMT) complication (n = 10), infection (n = 8), liver disease (n = 4), cancer (n = 3), thromboembolism (n = 2) and severe anemia (n = 1). There was a steady decline in the number of deaths due to heart disease from the year 2000 onwards and no death from BMT was observed after the year 2010. A progressive decrease in the median age of BMT was observed in younger birth cohorts (p < 0.001). A total of 480 (67.7%) patients developed ≥1 complication. Patients in younger birth cohorts demonstrated better complication-free survival (p < 0.001) which was comparable between sexes (p = 0.230). Independent risk factors for death in multivariate analysis included heart disease (HR: 4.63, 95%CI: 1.78-12.1, p = 0.002), serum ferritin >1000 ng/mL (HR: 15.5, 95%CI: 3.52-68.2, p < 0.001), male sex (HR: 2.75, 95%CI: 0.89-8.45, p = 0.078), and splenectomy (HR: 6.97, 95%CI: 0.90-54.0, p < 0.063). Survival in patients with ß-thalassemia major continues to improve with adequate access to care, best practice sharing, continued research, and collaboration between centers.
Assuntos
Cardiopatias , Tromboembolia , Talassemia beta , Feminino , Humanos , Masculino , Adulto Jovem , Adulto , Talassemia beta/complicações , Talassemia beta/terapia , Transplante de Medula Óssea , Fatores de Risco , Tromboembolia/complicaçõesRESUMO
BACKGROUND: Hydroxyurea (HU) has been widely used in clinical practice to manage patients with non-transfusion dependent thalassemia (NTDT). Few data are available about the effects of its administration in Italian patients. We assessed hematological and non-hematological outcomes following short- and long-term exposure to HU. RESEARCH DESIGN AND METHODS: We considered 71 NTDT patients (30 females) enrolled in the Myocardial Iron Overload in Thalassemia Network and treated for >12 months with HU. RESULTS: The mean duration of HU treatment was 8.23±5.79 years, starting at a mean age of 37.02±12.06 years. A significant increase in hemoglobin and mean corpuscular volume values and a down-regulation of all erythropoietic and/or hemolysis indices were detected after at least 12 months of treatment. In 28 patients the hemoglobin increase was ≥1.0 g/dl, associated with a higher HU dose. The hematological response dropped in long-term treatment. A favorable impact of HU treatment in limiting the progression of several complications typical of NTDT syndrome was observed. CONCLUSION: Our findings seemed to suggest that in several NTDT patients HU could be still a valid option to limit the advance in overall disease clinical burden without carrying significant adverse events and increase in mortality.
Assuntos
Hidroxiureia , Talassemia , Talassemia beta , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Talassemia beta/tratamento farmacológico , Hemoglobinas , Hidroxiureia/efeitos adversos , Hidroxiureia/uso terapêutico , Talassemia/tratamento farmacológicoRESUMO
Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies. Although we observed a similar proportion of Caucasian (47.9%) and African (48.7%) patients, Italian SCD patients clustered into two distinct overall groups: children of African descent and adults of Caucasian descent. We found a subset of SCD patients requiring more intensive therapy with a combination of HC plus chronic transfusion regimen, due to partial failure of HC treatment alone in preventing or reducing sickle cell-related acute manifestations. Notably, we observed a higher use of acute transfusion approaches for SCD patients of African descent when compared to Caucasian subjects. This might be related to (i) age of starting HC treatment; (ii) patients' low social status; (iii) patients' limited access to family practitioners; or (iv) discrimination. In our cohort, alloimmunization was documented in 135 patients (8.5%) and was more common in Caucasians (10.3%) than in Africans (6.6%). Alloimmunization was similar in male and female and more frequent in adults than in children. Our study reinforces the importance of donor-recipient exact matching for ABO, Rhesus, and Kell antigen systems for RBC compatibility as a winning strategy to avoid or limit alloimmunization events that negatively impact the clinical management of SCD-related severe complications. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03397017.
RESUMO
Although numerous patient-specific co-factors have been shown to be associated with worse outcomes in COVID-19, the prognostic value of thalassaemic syndromes in COVID-19 patients remains poorly understood. We studied the outcomes of 137 COVID-19 patients with a history of transfusion-dependent thalassaemia (TDT) and transfusion independent thalassaemia (TIT) extracted from a large international cohort and compared them with the outcomes from a matched cohort of COVID-19 patients with no history of thalassaemia. The mean age of thalassaemia patients included in our study was 41 ± 16 years (48.9% male). Almost 81% of these patients suffered from TDT requiring blood transfusions on a regular basis. 38.7% of patients were blood group O. Cardiac iron overload was documented in 6.8% of study patients, whereas liver iron overload was documented in 35% of study patients. 40% of thalassaemia patients had a history of splenectomy. 27.7% of study patients required hospitalization due to COVID-19 infection. Amongst the hospitalized patients, one patient died (0.7%) and one patient required intubation. Continuous positive airway pressure (CPAP) was required in almost 5% of study patients. After adjustment for age-, sex- and other known risk factors (cardiac disease, kidney disease and pulmonary disease), the rate of in-hospital complications (supplemental oxygen use, admission to an intensive care unit for CPAP therapy or intubation) and all-cause mortality was significantly lower in the thalassaemia group compared to the matched cohort with no history of thalassaemia. Amongst thalassaemia patients in general, the TIT group exhibited a higher rate of hospitalization compared to the TDT group (p = 0.001). In addition, the rate of complications such as acute kidney injury and need for supplemental oxygen was significantly higher in the TIT group compared to the TDT group. In the multivariable logistic regression analysis, age and history of heart or kidney disease were all found to be independent risk factors for increased in-hospital, all-cause mortality, whereas the presence of thalassaemia (either TDT or TIT) was found to be independently associated with reduced all-cause mortality. The presence of thalassaemia in COVID-19 patients was independently associated with lower in-hospital, all-cause mortality and few in-hospital complications in our study. The pathophysiology of this is unclear and needs to be studied in vitro and in animal models.
Assuntos
COVID-19 , Sobrecarga de Ferro , Talassemia , COVID-19/complicações , Feminino , Hospitais , Humanos , Sobrecarga de Ferro/etiologia , Masculino , Oxigênio , Sistema de Registros , Talassemia/complicações , Talassemia/terapiaAssuntos
COVID-19/complicações , Hemoglobinopatias/complicações , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/mortalidade , Feminino , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/mortalidade , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Talassemia/complicações , Talassemia/epidemiologia , Talassemia/mortalidade , Adulto JovemRESUMO
AIMS: A tailored chelation therapy guided by magnetic resonance imaging (MRI) is a strategy to improve the prognosis in iron-loaded patients, in many cases still hampered by limited MRI availability. In order to address this issue, the Myocardial Iron Overload in Thalassemia (MIOT) network was established in Italy and we aimed to describe the impact of 10-year activity of this network on cardiac burden in thalassemia major (TM). METHODS AND RESULTS: Within the MIOT network, 1746 TM patients (911 females; mean age 31.2 ± 9.1 years) were consecutively enrolled and prospectively followed by 70 thalassemia and 10 MRI centres. Patients were scanned using a multiparametric approach for assessing myocardial iron overload (MIO), biventricular function, and myocardial fibrosis. At the last MRI scan, a significant increase in global heart T2* values and a significantly higher frequency of patients with no MIO (all segmental T2* ≥20 ms) were detected, with a concordant improvement in biventricular function, particularly in patients with baseline global heart T2* <20 ms. Forty-seven percentage of patients changed the chelation regimen based on MRI. The frequency of heart failure (HF) significantly decreased after baseline MRI from 3.5 to 0.8% (P < 0.0001). Forty-six patients died during the study, and HF accounted for 34.8% of deaths. CONCLUSION: Over 10 years, continuous monitoring of cardiac iron and a tailored chelation therapy allowed MIO reduction, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. A national networking for rare diseases therefore proved effective in improving the care and reducing cardiac outcomes of TM patients.
Assuntos
Sobrecarga de Ferro , Talassemia , Talassemia beta , Adulto , Feminino , Humanos , Ferro , Imageamento por Ressonância Magnética/métodos , Imagem Cinética por Ressonância Magnética/métodos , Miocárdio/patologia , Doenças Raras , Talassemia/complicações , Talassemia/patologia , Adulto Jovem , Talassemia beta/complicações , Talassemia beta/terapiaRESUMO
BACKGROUND: The causes and effects of genotypic heterogeneity in beta-thalassemia major (ß-TM) have not been fully investigated. The aim of this multicentre study was to determine whether different genotype groups could predict the development of cardiovascular magnetic resonance abnormalities and cardiac complications. MATERIALS AND METHODS: We considered 708 ß-TM patients (373 females, age 30.05±9.47 years) consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network. Data were collected from birth to the first cardiac magnetic resonance scan. Myocardial iron overload was assessed using a T2* technique. Biventricular function was quantified by cine images. Macroscopic myocardial fibrosis was evaluated by a late gadolinium enhancement technique. RESULTS: Three groups of patients were identified: ß+ homozygotes (n=158), ß+/ß° heterozygotes (n=298) and ß° homozygotes (n=252). Compared to ß+ homozygotes, the other two groups showed a significantly higher risk of myocardial iron overload and left ventricular dysfunction. We recorded 90 (13.0%) cardiac events: 46 episodes of heart failures, 38 arrhythmias (33 supraventricular, 3 ventricular and 2 hypokinetic) and 6 cases of pulmonary hypertensions. ß° homozygotes showed a significantly higher risk than ß+ homozygotes of arrhythmias and cardiac complications considered globally. DISCUSSION: Different genotype groups predicted the development of myocardial iron overload, left ventricular dysfunction, arrhythmias and cardiac complications in ß-TM patients. These data support the importance of genotype knowledge in the management of ß-TM patients.
Assuntos
Doenças Cardiovasculares/etiologia , Talassemia beta/complicações , Adulto , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/genética , Feminino , Predisposição Genética para Doença , Humanos , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Adulto Jovem , Talassemia beta/genéticaRESUMO
Beta thalassemia major (ß-TM) displays a great deal of phenotypic heterogeneity, not fully investigated in terms of cause-effect. We aimed to detect if different genotypic groups could be related to different levels of cardiac impairment, evaluated by cardiovascular magnetic resonance (CMR). We considered 671 ß-TM patients (age 30.1â¯years, 52.9% females) consecutively enrolled in the Myocardial Iron Overload (MIO) in Thalassemia network. MIO was assessed by T2* technique. Biventricular function was quantified by cine images. Myocardial fibrosis was evaluated by late gadolinium enhancement (LGE) technique. Three groups of patients were identified: heterozygotes ß+/ß° (Nâ¯=â¯279), homozygotes ßâ¯+â¯(Nâ¯=â¯154), homozygotes ß° (Nâ¯=â¯238). Transfusional needs resulted significantly lower in homozygous ßâ¯+â¯TM patients when compared to the other groups. The homozygous ßâ¯+â¯group versus the heterozygous and homozygous ß° groups showed higher global heart T2* values (Pâ¯<â¯0.0001) and a lower number of patients with a global heart T2* value<20â¯ms (Pâ¯<â¯0.001). The homozygotes ßâ¯+â¯showed a lower number of patients with a pathological left ventricular ejection fraction (LVEF) than the other two groups (Pâ¯<â¯0.05). The ß+/ßâ¯+â¯TM patients showed less MIO and a concordant better systolic heart function. These data support the knowledge of different genotypic groups in the management of ß-TM patients.
Assuntos
Genótipo , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Imageamento por Ressonância Magnética , Globinas beta/genética , Talassemia beta/complicações , Talassemia beta/genética , Adulto , Alelos , Biomarcadores , Transfusão de Sangue , Índices de Eritrócitos , Feminino , Testes de Função Cardíaca , Humanos , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/terapia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Talassemia beta/diagnóstico , Talassemia beta/terapiaRESUMO
We prospectively assessed the efficacy of deferasirox versus deferiprone or desferrioxamine as monotherapy in thalassaemia major (TM) patients by magnetic resonance imaging (MRI). We selected the patients enrolled in the Myocardial Iron Overload in Thalassaemia network who received only one chelator between two MRIs (deferasirox = 235, deferiprone = 142, desferrioxamine = 162). Iron overload was measured by T2* technique and biventricular function by cine images. Among the patients with baseline myocardial iron, in all three groups there was a significant improvement in global heart T2* values. The deferiprone and desferrioxamine groups showed a significant improvement in left ventricular ejection fraction (LVEF). Only the deferiprone group showed a significant improvement in right ventricular ejection fraction (RVEF). The improvement in global heart T2* was significantly lower in the deferasirox versus the deferiprone group. The improvement in the LVEF was significantly higher in the deferiprone and desferrioxamine groups than in the deferasirox group and the improvement in the RVEF was significantly higher in the deferiprone than in deferasirox group. Among the patients with baseline hepatic iron, the changes in hepatic iron were comparable in deferasirox versus the other groups. Deferasirox monotherapy was less effective than deferiprone in improving myocardial siderosis and biventricular function and less effective than desferrioxamine in improving the LVEF.
Assuntos
Deferasirox/uso terapêutico , Deferiprona/uso terapêutico , Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Talassemia beta/tratamento farmacológico , Adulto , Cardiomiopatias/complicações , Cardiomiopatias/tratamento farmacológico , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Estudos Prospectivos , Resultado do Tratamento , Talassemia beta/complicaçõesRESUMO
OBJECTIVES: The liver remains the primary site of iron storage, with liver iron concentration (LIC) being a strong surrogate of total body iron. MRI-R2 can accurately measure LIC. The LICNET (Liver Iron Cutino Network) was established to diagnostics of liver iron overload by MRI-R2 subjects with hemochromatosis in hematological disorders. The aims of the study were to look at variation in LIC measurements during time across different chelation regimens. METHODS: This was a cross-sectional study of 130 patients attending 9 Italian centers participating in the LICNET. LIC comparisons over time (T0 and T1 ) were made using t test and/or Wilcoxon test. RESULTS: LIC significantly decreased from MRI1 to MRI2 although at high variance (median change -0.8 mg Fe/g dw, range: -29.0 to 33.0; P = .011) and 7.7% of patients shifted from LIC values of high risk (>15 mg Fe/g dw) to an intermediate-risk category (7-15 mg Fe/g dw). Median change in LIC and correlation with serum ferritin levels (SF), during different chelation regimens, is reported. CONCLUSIONS: These findings suggest as longitudinal variation in the LIC is possible, across all chelation regimens. It confirms as SF levels not always can be used for estimating changes in LIC.
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Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Ferro/metabolismo , Fígado/metabolismo , Fígado/patologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Terapia por Quelação , Criança , Estudos Transversais , Feminino , Ferritinas/sangue , Humanos , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/diagnóstico por imagem , Sobrecarga de Ferro/etiologia , Fígado/diagnóstico por imagem , Fígado/efeitos dos fármacos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Progression of liver fibrosis in patients with hemoglobinopathies is strongly related to the severity of iron overload and the presence of chronic hepatitis C virus (HCV) infection. Effective iron chelation therapy and HCV infection eradication may prevent liver complications. The European Association for the Study of the Liver guidelines recommend interferon-free regimens for the treatment of HCV infection in patients with hemoglobinopathies. However, data regarding the use of direct-acting antiviral drugs (DAAs) in this patient population are few. This observational study evaluated the safety and efficacy of therapy with DAAs in an Italian cohort of patients with hemoglobinopathies, chronic HCV infection and advanced liver fibrosis. Between March 2015 and December 2016, 139 patients received DAAs and completed 12 weeks of follow up after the end of treatment for the evaluation of sustained virological response (12SVR). The 12SVR (93.5%) was comparable with that typically observed in cirrhotic patients without hemoglobinopathies. Three patients died during the period of observation of causes unrelated to DAAs. One patient did not achieve a virological response and five (3.6%) relapsed during 12 weeks of follow-up after the end of therapy. In addition, patients showed significant reductions in serum ferritin at 12 weeks to levels similar to those observed in a control group of 39 patients with thalassemia major without HCV infection, who adhered to chelation therapy and had no overt iron overload. In conclusion, the use of DAAs appears to be safe and effective in patients with hemoglobinopathies and advanced liver disease due to HCV.
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Antivirais/uso terapêutico , Hemoglobinopatias/complicações , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Adulto , Antivirais/efeitos adversos , Antivirais/farmacologia , Feminino , Hepatite C Crônica/complicações , Humanos , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/complicações , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Real-life data on the use of R2 MRI for the assessment of liver iron concentration (LIC) remain limited. METHODS: We conducted a cross-sectional analysis on 363 patients (mean age 35.6 yr, 44.1% men) with hemoglobinopathies (204 ß-thalassemia major [TM], 102 ß-thalassemia intermedia [TI], and 57 sickle cell disease [SCD]) that were evaluated with R2 MRI as part of LICNET, an MRI network of 13 Italian treatment centers. RESULTS: The mean LIC was 7.8 mg/g (median: 4.0), with high LIC (>7 mg/g) noted in both transfused (TM, TI 37%; SCD 38%) and non-transfused (TI 20%) patients. Ferritin levels correlated with LIC in both transfused (TM, TI, SCD) and non-transfused (TI) patients (P < 0.001), although lower values predicted high LIC in non-transfused patients (1900 vs. 650 ng/mL in TM vs. non-transfused TI). A correlation between LIC and ALT levels was only noted in HCV-negative patients (rs = 0.316, P < 0.001). The proportion of patients with high LIC was significantly different between iron chelators used (P = 0.023), with the lowest proportion in deferasirox (30%) and highest in deferiprone (53%)-treated patients. CONCLUSIONS: High LIC values persist in subgroups of patients with hemoglobinopathy, warranting closer monitoring and management optimization, even for non-transfused patients with relatively low ferritin levels.
Assuntos
Hemoglobinopatias/complicações , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/etiologia , Ferro/metabolismo , Fígado/metabolismo , Fígado/patologia , Imageamento por Ressonância Magnética , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Biomarcadores , Criança , Comorbidade , Estudos Transversais , Feminino , Ferritinas/sangue , Hemoglobinopatias/diagnóstico , Humanos , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Dysmetabolic iron overload syndrome is a rare event causing hepatic impairment with serious long-term side effects. Here, we describe a case of metabolic syndrome-related hepatic iron overload that showed a rapid, effective, and safe response to erythrocytapheresis. J. Clin. Apheresis 31:443-447, 2016. © 2015 Wiley Periodicals, Inc.
Assuntos
Citaferese , Transfusão de Eritrócitos/normas , Sobrecarga de Ferro/terapia , Hepatopatias/metabolismo , Humanos , Sobrecarga de Ferro/complicações , Hepatopatias/etiologia , Síndrome Metabólica , Segurança do PacienteRESUMO
The aim of this study was to evaluate, in a large cohort of chronically transfused patients, whether the presence of extramedullary hematopoiesis (EMH) accounts for the typical patterns of cardiac iron distribution and/or cardiac function parameters. We retrospectively selected 1,266 thalassemia major patients who had undergone regular transfusions (611 men and 655 women; mean age: 31.3 ± 8.9 years, range: 4.2-66.6 years) and were consecutively enrolled within the Myocardial Iron Overload in Thalassemia network. The presence of EMH was evaluated based on steady-state free precession sequences; cardiac and liver iron overloads were quantified using a multiecho T2* approach; cardiac function parameters and pulmonary diameter were quantified using the steady-state free precession sequences; and myocardial fibrosis was evaluated using the late gadolinium enhancement technique. EMH was detected in 167 (13.2%) patients. The EMH+ patients had significantly lower cardiac iron overload than that of the EMH- patients (P = 0.003). The patterns of cardiac iron distribution were significantly different in the EMH+ and EMH- patients (P < 0.0001), with a higher prevalence of patients with no myocardial iron overload and heterogeneous myocardial iron overload and no significant global heart iron in the EMH+ group EMH+ patients had a significantly higher left ventricle mass index (P = 0.001) and a significantly higher pulmonary artery diameter (P = 0.002). In conclusion, in regularly transfused thalassemia patients, EMH was common and was associated with a thalassemia intermedia-like pattern of cardiac iron deposition despite regular transfusion therapy.
Assuntos
Hematopoese Extramedular , Sobrecarga de Ferro/metabolismo , Ferro/metabolismo , Miocárdio/metabolismo , Reação Transfusional , Talassemia beta/metabolismo , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , Feminino , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Estudos Retrospectivos , Talassemia beta/patologia , Talassemia beta/terapiaRESUMO
Thalassaemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia. Organ damage caused by iron overload represents the major cause of illness and the heart complications secondary to extensive myocardial iron overload are the leading cause of mortality. These patients are generally not considered as candidates for heart transplantation. We report a case of a patient with thalassemia intermedia (TI) with severe cardiac dysfunction and severe aortic stenosis who underwent percutaneous aortic valve replacement (PARV). PARV was a safe and a valid therapeutic approach dramatically to improve the clinical evolution of cardiomyopathies in our patient.