Extramedullary haematopoiesis in patients with thalassemia: a cross-sectional description of its prevalence, clinical features and survival.

INTRODUCTION: Despite knowledge advances on extramedullary haematopoiesis (EMH) in thalassemic patients, the real picture remains an open issue. OBJECTIVES: To assess EMH prevalence in patients with thalassemia major (TM) and intermedia (TI), to describe magnetic resonance imaging (MRI) findings and to explore clinical risk factors. METHODS: In this cross-sectional study, images and clinical records of 184 consecutive patients with thalassemia who underwent T2* MRI between 2004 and 2011 were reviewed. Association of EMH with survival was investigated for patients with available follow-up charts. RESULTS: EMH was detected in 16/168 (9.5%) patients with TM (aged 19-49 years) and in 3/16 (18.8%) with TI (aged 36-41 years). Most (88%) had paravertebral thoracic and/or abdominal masses. Age was significantly associated with EMH risk (hazard ratio, [HR] 1.10/year; confidence interval [CI]: 1.03-1.18; p-value < 0.001), while lower pancreatic iron content by T2*MRI (HR: 0.94/ms; CI: 0.89-0.99; p-value = 0.049) was a protective factor. Estimated survival rate was superior for EMH-positive (n = 19) when compared to EMH-negative patients (n = 75) (p-value = 0.013). CONCLUSIONS: The prevalence of EMH was 10.3% (19/184), presented mainly as tumoral masses of 3 to 10 cm. Age was a risk factor for EMH development, while lower pancreatic iron might be a protective factor in this cohort.

Cardiac iron overload evaluation in thalassaemic patients using T2* magnetic resonance imaging following chelation therapy: a multicentre cross-sectional study

Abstract Introduction Magnetic resonance imaging (MRI) T2* technique is used to assess iron overload in the heart, liver and pancreas of thalassaemic patients. Optimal iron chelation and expected tissue iron response rates remain under investigation. The objective of this study was to analyse serum ferritin and the iron concentration in the heart, liver and pancreas measured by MRI T2*/R2* during regular chelation therapy in a real-world cohort of patients with thalassemia. Methods We evaluated thalassaemic patients ≥ 7 years old undergoing chelation/transfusion therapy by MRI and assessed serum ferritin at baseline and follow-up from 2004-2011. Results We evaluated 136 patients, 92% major thalassaemic, with a median age of 18 years, and median baseline ferritin 2.033ng/ml (range: 59-14,123). Iron overload distribution was: liver (99%), pancreas (74%) and heart (36%). After a median of 1.2 years of follow-up, the iron overload in the myocardium reduced from 2,63 Fe mg/g to 2,05 (p 0.003). The optimal R2* pancreas cut-off was 148 Hertz, achieving 78% sensitivity and 73% specificity. However, when combining the R2* pancreas cut off ≤ 50 Hertz and a ferritin ≤ 1222 ng/ml, we could reach a negative predictive value (NPV) of 98% for cardiac siderosis. Only 28% were undergoing combined chelation at baseline assessment, which increased up to 50% on follow up evaluation. Conclusions Chelation therapy significantly reduced cardiac siderosis in thalassaemic patients. In patients with moderate/severe liver iron concentration undergoing chelation therapy, ferritin levels and myocardium iron improved earlier than the liver siderosis.

Cardiac iron overload evaluation in thalassaemic patients using T2* magnetic resonance imaging following chelation therapy: a multicentre cross-sectional study.

INTRODUCTION: Magnetic resonance imaging (MRI) T2* technique is used to assess iron overload in the heart, liver and pancreas of thalassaemic patients. Optimal iron chelation and expected tissue iron response rates remain under investigation. The objective of this study was to analyse serum ferritin and the iron concentration in the heart, liver and pancreas measured by MRI T2*/R2* during regular chelation therapy in a real-world cohort of patients with thalassemia. METHODS: We evaluated thalassaemic patients ≥ 7 years old undergoing chelation/transfusion therapy by MRI and assessed serum ferritin at baseline and follow-up from 2004-2011. RESULTS: We evaluated 136 patients, 92% major thalassaemic, with a median age of 18 years, and median baseline ferritin 2.033ng/ml (range: 59-14,123). Iron overload distribution was: liver (99%), pancreas (74%) and heart (36%). After a median of 1.2 years of follow-up, the iron overload in the myocardium reduced from 2,63 Fe mg/g to 2,05 (p 0.003). The optimal R2* pancreas cut-off was 148 Hertz, achieving 78% sensitivity and 73% specificity. However, when combining the R2* pancreas cut off ≤ 50 Hertz and a ferritin ≤ 1222 ng/ml, we could reach a negative predictive value (NPV) of 98% for cardiac siderosis. Only 28% were undergoing combined chelation at baseline assessment, which increased up to 50% on follow up evaluation. CONCLUSIONS: Chelation therapy significantly reduced cardiac siderosis in thalassaemic patients. In patients with moderate/severe liver iron concentration undergoing chelation therapy, ferritin levels and myocardium iron improved earlier than the liver siderosis.

Brazilian Thalassemia Association protocol for iron chelation therapy in patients under regular transfusion.

In the absence of an iron chelating agent, patients with beta-thalassemia on regular transfusions present complications of transfusion-related iron overload. Without iron chelation therapy, heart disease is the major cause of death; however, hepatic and endocrine complications also occur. Currently there are three iron chelating agents available for continuous use in patients with thalassemia on regular transfusions (desferrioxamine, deferiprone, and deferasirox) providing good results in reducing cardiac, hepatic and endocrine toxicity. These practice guidelines, prepared by the Scientific Committee of Associação Brasileira de Thalassemia (ABRASTA), presents a review of the literature regarding iron overload assessment (by imaging and laboratory exams) and the role of T2* magnetic resonance imaging (MRI) to control iron overload and iron chelation therapy, with evidence-based recommendations for each clinical situation. Based on this review, the authors propose an iron chelation protocol for patients with thalassemia under regular transfusions.

Brazilian Thalassemia Association protocol for iron chelation therapy in patients under regular transfusion

In the absence of an iron chelating agent, patients with beta-thalassemia on regular transfusions present complications of transfusion-related iron overload. Without iron chelation therapy, heart disease is the major cause of death; however, hepatic and endocrine complications also occur. Currently there are three iron chelating agents available for continuous use in patients with thalassemia on regular transfusions (desferrioxamine, deferiprone, and deferasirox) providing good results in reducing cardiac, hepatic and endocrine toxicity. These practice guidelines, prepared by the Scientific Committee of Associação Brasileira de Thalassemia (ABRASTA), presents a review of the literature regarding iron overload assessment (by imaging and laboratory exams) and the role of T2* magnetic resonance imaging (MRI) to control iron overload and iron chelation therapy, with evidence-based recommendations for each clinical situation. Based on this review, the authors propose an iron chelation protocol for patients with thalassemia under regular transfusions.

Pancreatic iron stores assessed by magnetic resonance imaging (MRI) in beta thalassemic patients.

PURPOSE: To assess the correlation between MRI findings of the pancreas with those of the heart and liver in patients with beta thalassemia; to compare the pancreas T2* MRI results with glucose and ferritin levels and labile plasma iron (LPI). MATERIALS AND METHODS: We retrospectively evaluated chronically transfused patients, testing glucose with enzymatic tests, serum ferritin with chemiluminescence, LPI with cellular fluorescence, and T2* MRI to assess iron content in the heart, liver, and pancreas. MRI results were compared with one another and with serum glucose, ferritin, and LPI. Liver iron concentration (LIC) was determined in 11 patients' liver biopsies by atomic absorption spectrometry. RESULTS: 289 MRI studies were available from 115 patients during the period studied. 9.4% of patients had overt diabetes and an additional 16% of patients had impaired fasting glucose. Both pancreatic and cardiac R2* had predictive power (p<0.0001) for identifying diabetes. Cardiac and pancreatic R2* were modestly correlated with one another (r(2) = 0.20, p<0.0001). Both were weakly correlated with LIC (r(2) = 0.09, p<0.0001 for both) and serum ferritin (r(2) = 0.14, p<0.0001 and r(2) = 0.03, p<0.02, respectively). None of the three served as a screening tool for single observations. There is a strong log-log, or power-law, relationship between ratio of signal intensity (SIR) values and pancreas R2* with an r(2) of 0.91. CONCLUSIONS: Pancreatic iron overload can be assessed by MRI, but siderosis in other organs did not correlate significantly with pancreatic hemosiderosis.

Sobrecarga de ferro em pacientes talassêmicos brasileiros / Iron overload in Brazilian thalassemic patients

Objectives: To evaluate the use of magnetic resonance imaging in patients with Beta-thalassemia and to compare T2* magnetic resonance imaging results with serum ferritin levels and the redox active fraction of labile plasma iron. Methods: We have retrospectively evaluated 115 chronically transfused patients (65 women). We tested serum ferritin with chemiluminescence, fraction of labile plasma iron by cellular fluorescence and used T2* MRI to assess iron content in the heart, liver, and pancreas. Hepatic iron concentration was determined in liver biopsies of 11 patients and the results were compared with liver T2* magnetic resonance imaging. Results: The mean serum ferritin was 2,676.5+/- 2,051.7ng/mL. A fraction of labile plasma iron was abnormal (> 0,6 Units/mL) in 48/83 patients (57%). The mean liver T2* value was 3.91 ± 3.95 ms, suggesting liver siderosis in most patients (92.1%). The mean myocardial T2* value was 24.96 ± 14.17 ms and the incidence of cardiac siderosis (T2* < 20 ms) was 36%, of which 19% (22/115) were severe cases (T2* < 10 ms). The mean pancreas T2* value was 11.12 ± 11.20 ms, and 83.5% of patients had pancreatic iron deposition (T2* < 21 ms). There was significant curvilinear and inverse correlation between liver T2* magnetic resonance imaging and hepatic iron concentration (r= -0.878; p < 0.001) and moderate correlation between pancreas and myocardial T2* MRI (r = 0.546; p < 0.0001). Conclusion: A high rate of hepatic, pancreatic and cardiac impairment by iron overload was demonstrated. Ferritin levels could not predict liver, heart or pancreas iron overload as measured by T2* magnetic resonance imaging. Therewas no correlation between liver, pancreas, liver and myocardial iron overload, neither between ferritin and fraction of labile plasma iron with liver, heart and pancreas T2* values.

Objetivo: Avaliar o acúmulo de ferro em diferentes órgãos por meio da ressonância nuclear magnética T2* e correlacionar os resultados aos níveis de ferritina sérica, ferro plasmático lábil e outros órgãos envolvidos. Métodos: Foram avaliados retrospectivamente 115 pacientes talassêmicos (sendo 65 mulheres). A concentração hepática de ferro foi determinada em biópsia de 11 pacientes; os resultados foram comparados com os valores de T2* fígado. Resultados: a ferritina sérica média foi de 2.676,5 +/- 2.051,7 ng/mL. O ferro plasmático lábil foi anormal (> 0,6 Unidades/mL) em 48/83 pacientes (57%). A média dos valores de T2* no fígado foi 3,91 ± 3,95 ms, sugerindo siderose hepática em 92,1% pacientes. A média do T2* cardíaco foi de 24,96 ± 14,17 ms e 36% dos pacientes apresentavam siderose cardíaca (T2* < 20ms), dos quais 19% (22/115) já apresentavam sobrecarga cardíaca grave (T2* < 10 ms). A média de T2* no pâncreas foi de 11,12 ± 11,20 ms, perfazendo um total de 83,5% de pacientes com sobrecarga de ferro pancreático (T2* < 21 ms). Houve correlação significativa, curvilínea e inversa entre T2* fígado e a concentração de ferro hepática (r = -0,878; p <0,001) e correlação moderada entre T2* pâncreas e T2* miocárdio (r = 0,546; p<0,0001). Conclusão: Uma elevada taxa de acometimento hepático, pancreático e cardíaco por sobrecarga férrica foi demonstrada. Os níveis de ferritina não puderam prever sobrecarga de ferro hepático, cardíaco ou pancreáticos medidos por meio da ressonância nuclear magnética T2*. Não houve correlação entre a sobrecarga de ferro no fígado, pâncreas e miocárdio, nem entre a ferritina e os níveis plasmáticos de ferro sérico e os valores de T2* no fígado, coração e pâncreas.

Iron overload in Brazilian thalassemic patients.

UNLABELLED: ABSTRACTObjectives:To evaluate the use of magnetic resonance imaging in patients with ß-thalassemia and to compare T2* magnetic resonance imaging results with serum ferritin levels and the redox active fraction of labile plasma iron. METHODS: We have retrospectively evaluated 115 chronically transfused patients (65 women). We tested serum ferritin with chemiluminescence, fraction of labile plasma iron by cellular fluorescence and used T2* MRI to assess iron content in the heart, liver, and pancreas. Hepatic iron concentration was determined in liver biopsies of 11 patients and the results were compared with liver T2* magnetic resonance imaging. RESULTS: The mean serum ferritin was 2,676.5 +/- 2,051.7 ng/mL. A fraction of labile plasma iron was abnormal (> 0,6 Units/mL) in 48/83 patients (57%). The mean liver T2* value was 3.91 ± 3.95 ms, suggesting liver siderosis in most patients (92.1%). The mean myocardial T2* value was 24.96 ± 14.17 ms and the incidence of cardiac siderosis (T2* < 20 ms) was 36%, of which 19% (22/115) were severe cases (T2* < 10 ms). The mean pancreas T2* value was 11.12 ± 11.20 ms, and 83.5% of patients had pancreatic iron deposition (T2* < 21 ms). There was significant curvilinear and inverse correlation between liver T2* magnetic resonance imaging and hepatic iron concentration (r= -0.878; p < 0.001) and moderate correlation between pancreas and myocardial T2* MRI (r = 0.546; p < 0.0001). CONCLUSION: A high rate of hepatic, pancreatic and cardiac impairment by iron overload was demonstrated. Ferritin levels could not predict liver, heart or pancreas iron overload as measured by T2* magnetic resonance imaging. There was no correlation between liver, pancreas, liver and myocardial iron overload, neither between ferritin and fraction of labile plasma iron with liver, heart and pancreas T2* values.

[Prevalence of hepatitis C infection in patients with type 2 diabetes mellitus]. / Prevalência de infecção pelo vírus da hepatite C em pacientes com diabetes melito tipo 2.

BACKGROUND: Recently, a possible epidemiological association between hepatitis C virus infection and diabetes mellitus has been suggested and a higher prevalence of HCV antibodies has been found among type 2 diabetic when compared with normal controls. AIM: To evaluate the prevalence of hepatitis C infection in diabetic patients in Curitiba, PR, Brazil. PATIENTS AND METHODS: A total of 145 type 2 and 104 type 1 diabetic patients attending the outpatient diabetic unit of an university hospital were consecutively tested for anti-HCV, using a fourth-generation enzyme-linked immunosorbent assay (ELISA). The control group was constituted by 16,720 volunteer blood donors attending the blood bank of the same hospital during the period of the study. Diabetic patients were also evaluated for clinical, biochemical (aminotransferase levels) and demographic variables and previous exposure to risk factors for hepatitis C infection. RESULTS: A higher prevalence of hepatitis C infection was observed in type 2 diabetic patients in comparison with blood donors. Although anti-HCV prevalence in type 2 diabetic patients was higher than found in type 1, it did not reach statistical significance. Both diabetic groups were predominantly female, and as expected, type 2 diabetic were older than type 1. Race distribution, duration of the disease, and previous exposure to hepatitis C risk factors were similar in both groups, but type 2 diabetic subjects had higher median levels of alanine aminotransferase than type 1. CONCLUSIONS: A higher prevalence of hepatitis C infection was detected in type 2 diabetic patients in comparison with blood donors in our region, in accordance with study data from different populations. If all type 2 diabetic patients should undergo regular screening for hepatitis C infection remains a question.

Prevalência de infecção pelo vírus da hepatite C em pacientes com diabetes melito tipo 2 / Prevalence of hepatitis C infection in patients with type 2 diabetes mellitus

RACIONAL: Estudos recentes têm sugerido possível associação entre infecção pelo vírus da hepatite C (VHC) e diabetes melito tipo 2, relatando prevalência elevada de infecção pelo vírus C nessa população. OBJETIVO: Verificar a prevalência de infecção pelo VHC em adultos portadores de diabetes melito em nosso meio. MÉTODOS: Foram avaliados consecutivamente 145 adultos com diabetes melito tipo 2 e 104 com diabetes melito tipo 1, em acompanhamento no ambulatório de diabetes de um hospital universitário, quanto à presença de anticorpos contra VHC (anti-VHC) por método ELISA de quarta geração, utilizando como grupo controle 16 720 doadores de sangue da cidade de Curitiba, PR, no período em que foi realizada a pesquisa. Os pacientes diabéticos foram também avaliados quanto a dados demográficos, clínicos, bioquímicos (níveis séricos de aminotransferases) e exposição prévia a fatores de risco para infecção pelo VHC. RESULTADOS: Maior prevalência de positividade do anti-VHC foi observada em pacientes com diabetes melito tipo 2, em comparação aos doadores de sangue. A prevalência de anti-VHC naqueles com diabete melito tipo 2 foi superior à encontrada no tipo 1, embora não tenha alcançado significância estatística. Nos dois grupos de diabéticos houve predomínio do sexo feminino, sendo que os do tipo 2 apresentavam idade média superior aos do tipo 1. A distribuição de cor, tempo de diagnóstico do diabetes e a freqüência de exposição a fatores de risco foram semelhantes nos dois grupos. A mediana da taxa de alanina aminotransferase dos pacientes com diabetes tipo 2 foi superior à observada nos do tipo 1. CONCLUSÕES: Encontrou-se maior prevalência de infecção pelo VHC em diabéticos tipo 2 se comparado à população saudável de Curitiba, corroborando publicações prévias em outras populações.

BACKGROUND: Recently, a possible epidemiological association between hepatitis C virus infection and diabetes mellitus has been suggested and a higher prevalence of HCV antibodies has been found among type 2 diabetic when compared with normal controls. AIM: To evaluate the prevalence of hepatitis C infection in diabetic patients in Curitiba, PR, Brazil. PATIENTS AND METHODS: A total of 145 type 2 and 104 type 1 diabetic patients attending the outpatient diabetic unit of an university hospital were consecutively tested for anti-HCV, using a fourth-generation enzyme-linked immunosorbent assay (ELISA). The control group was constituted by 16,720 volunteer blood donors attending the blood bank of the same hospital during the period of the study. Diabetic patients were also evaluated for clinical, biochemical (aminotransferase levels) and demographic variables and previous exposure to risk factors for hepatitis C infection. RESULTS: A higher prevalence of hepatitis C infection was observed in type 2 diabetic patients in comparison with blood donors. Although anti-HCV prevalence in type 2 diabetic patients was higher than found in type 1, it did not reach statistical significance. Both diabetic groups were predominantly female, and as expected, type 2 diabetic were older than type 1. Race distribution, duration of the disease, and previous exposure to hepatitis C risk factors were similar in both groups, but type 2 diabetic subjects had higher median levels of alanine aminotransferase than type 1. CONCLUSIONS: A higher prevalence of hepatitis C infection was detected in type 2 diabetic patients in comparison with blood donors in our region, in accordance with study data from different populations. If all type 2 diabetic patients should undergo regular screening for hepatitis C infection remains a question.

Estudo multicêntrico da prevalência de infecçäo pelo vírus da hepatite C em doadores de sangue na cidade de Curitiba, Brasil / Multicenter study of hepatitis C virus infection prevalence in blood donors of Curitiba, Brazil

Visando avaliar a presença de anticorpos para o vírus da hepatite C em doadores voluntários dos principais bancos de sangue de Curitiba, PR, foram analisados 43.516 doadores, com a utilizaçäo de método de enzimoimunoensaio de terceira geração (Murex - marca registrada - version III, ABBOTT AxSYM - marca registrada - HCV version 3.0). O estudo detectou 347 casos positivos, o que corresponde à prevalência média de 0,80 por cento (variando de 0,64 por cento a 1,11 por cento). apenas 44 dos 347 pacientes anti-VHC positivos apresentaram alteraçäo da ALT (12,68 por cento). Estes baixos índices de elevaçäo da ALT deixam 303 casos restantes anti-VHC positivos com ALT normal (87,32 por cento), sugerindo a necessidade de se aplicar a eles o teste RIBA para confirmaçäo de positividade, uma vez que, segundo a literatura, apenas 30 por cento a 40 por cento destes seräo confirmados como positivos. A prevalência encontrada de anti-VHC em doadores de sangue em Curitiba se compara aos índices encontrados em outros centros de hemoterapia do Brasil.