Monica Verissimo

Amlodipine Reduces Cardiac Iron Overload in Patients with Thalassemia Major: A Pilot Trial

BACKGROUND Iron chelation therapy in patients with thalassemia major may not prevent iron overload in all organs, especially those in which iron enters cells through specific calcium channels. We designed a controlled pilot study to assess the potential of the calcium channel blocker amlodipine in strengthening the efficacy of iron chelation. METHODS Fifteen patients with thalassemia major undergoing chelation therapy were randomized to receive amlodipine added to standard treatment in a 1:2 allocation for 12 months. T2* values for assessment of iron overload in the liver and heart using magnetic resonance imaging were obtained at baseline and at 6 and 12 months. RESULTS In the amlodipine-treated group, heart T2* increased significantly in comparison to baseline at 6 and 12 months (21.7 ± 7.2 ms to 28.2 ± 7.9 ms and 28.3 ± 8.0 ms, with P = .007 and .03, respectively), while no differences were observed in the control group (25.1 ± 8.8 ms to 24.7 ± 7.8 ms and 26.2 ± 11.4 ms; P = .99 and 0.95, respectively); significant differences between groups were observed at 6 months (28.2 ± 7.9 ms vs 24.7 ± 7.8 ms in the control group, P = .03). A significant reduction in ferritin levels also was observed in the treated group at 12 months. CONCLUSIONS The use of amlodipine in conjunction with standard chelation therapy may suggest a new strategy in preventing and treating iron overload in patients with thalassemia major, especially in organs where iron absorption depends on active uptake by calcium channels like the heart.

Early cardiac iron overload in children with transfusion-dependent anemias

Quantitative magnetic resonance imaging (MRI) heart iron assessment has been an important advance in the follow-up of patients with transfusion-dependent anemias.[1][1] Few longitudinal data are available on the natural history of cardiac iron overload.[2][2] We refer this letter to the manuscript

A randomized trial of amlodipine in addition to standard chelation therapy in patients with thalassemia major

Cardiovascular disease resulting from iron accumulation is still a major cause of death in patients with thalassemia major (TM). Voltage-gated calcium-channel blockade prevents iron entry into cardiomyocytes and may provide an adjuvant treatment to chelation, reducing myocardial iron uptake. We evaluated whether addition of amlodipine to chelation strategies would reduce myocardial iron overload in TM patients compared with placebo. In a multicenter, double-blind, randomized, placebo-controlled trial, 62 patients were allocated to receive oral amlodipine 5 mg/day or placebo in addition to their current chelation regimen. The main outcome was change in myocardial iron concentration (MIC) determined by magnetic resonance imaging at 12 months, with patients stratified into reduction or prevention groups according to their initial T2* below or above the normal human threshold of 35 ms (MIC, 0.59 mg/g dry weight). At 12 months, patients in the reduction group receiving amlodipine (n = 15) had a significant decrease in MIC compared with patients receiving placebo (n = 15) with a median of -0.26 mg/g (95% confidence interval, -1.02 to -0.01) vs 0.01 mg/g (95% confidence interval, -0.13 to 0.23), P = .02. No significant changes were observed in the prevention group (treatment-effect interaction with P = .005). The same findings were observed in the subgroup of patients with T2* <20 ms. Amlodipine treatment did not cause any serious adverse events. Thus, in TM patients with cardiac siderosis, amlodipine combined with chelation therapy reduced cardiac iron more effectively than chelation therapy alone. Because this conclusion is based on subgroup analyses, it needs to be confirmed in ad hoc clinical trials. This trial was registered at www.clinicaltrials.gov identifier as #NCT01395199.

Heart and liver T2* assessment for iron overload using different software programs

ObjectivesTo assess the level of agreement and interchangeability among different software programs for calculation of T2* values for iron overload.MethodsT2* images were analysed in 60 patients with thalassaemia major using the truncation method in three software programs. Levels of agreement were assessed using Pearson correlation and Bland-Altman plots. Categorical classification for levels of iron concentration by each software program was also compared.ResultsFor the heart, all correlation coefficients were significant among the software programs (P < 0.001 for all coefficients). The mean differences and 95% limits of agreement were 0.2 (−4.73 to 5.0); 0.1 (−4.0 to 3.9); and −0.1 (−4.3 to 4.8). For the liver all correlations were also significant with P < 0.001. Bland-Altman plots showed differences of −0.02 (−0.7 to 0.6); 0.01 (−0.4 to 0.4); and −0.02 (−0.6 to 0.6). There were no significant differences in clinical classification among the software programs.ConclusionsAll tools used in this study provided very good agreement among heart and liver T2* values. The results indicate that interpretation of T2* data is interchangeable with any of the software programs tested.Key PointsMagnetic resonance imaging in iron overload assessment has become an essential tool.Post processing options to establish T2* values have not been compared.No differences were found on T2* of the liver or heart using 3 different techniques.Availability of these methods should allow more widespread interpretation of iron overload by MRI.

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.

Guidelines on the diagnosis of primary immune thrombocytopenia in children and adolescents: Associacao Brasileira de Hematologia, Hemoterapia e Terapia Celular Guidelines Project: Associacao Medica Brasileira - 2012

The guidelines project is a joint initiative of the Associacao Medica Brasileira and the Conselho Federal de Medicina. It aims to bring information together in medicine to standardize decisions in order to help strategies during diagnosis and treatment. These data were prepared and recommended by the Associacao Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH). Even though, all possible decisions should be evaluated by the physician responsible for diagnosis and treatment according to the patients setting and clinical status.

Crescimento e desenvolvimento nas doenças falciformes

Sickle cell patients present some characteristics in respect to growth and development that must be observed in their accompaniment. Growth is delayed from the age of two years old with the weight being affected more than the height. By adulthood, a normal height is attained but the weight remains lower than in a control population. Skeletal and sexual maturity is also delayed, with normalization occurring at an older age. Some factors contribute to this delay in growth and maturity including endocrine factors, chronic hemolysis and increased cardiovascular function that increases energy and protein expenditure and nutritional deficiencies. With the improvement of the accompaniment and treatment of sickle cell patients, it is possible to improve the quality of life with adequate monitoring of the growth and development.

Aplasia transitória da série vermelha na anemia falciforme

Sickle cell disease due to shortened life span of red blood cells by hemolysis, may present with severe anemia when erythropoietic suppression occurs due to infection by the Human parvovirus B19. The clinical presentation presents with fever, which may precede transient red cell aplasia, as well as laboratorial signs such as a drop in hemoglobin and significant reticulo cytopenia. Laboratorial diagnosis may be by immunofluorescence or enzymatic assays. Treatment is achieved by transfusion of packed red blood cells. Complications may be associated to this infection, including splenic and hepatic sequestration, acute chest syndrome, nephrotic syndrome, meningoencephalitis and strokes. Strategies of prevention are able to change the morbidity and mortality of this condition in sickle cell disease patients.

Guidelines on neonatal screening and painful vaso-occlusive crisis in sickle cell disease: Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular: Project guidelines: Associação Médica Brasileira - 2016

Josefina Aparecida Pellegrini Braga, Monica Pinheiro de Almeida Verissimo, Sara Teresinha Olalla Saad, Rodolfo Delfini Cancado, Sandra Regina Loggetto a Escola Paulista de Medicina, Universidade Federal de Sao Paulo (Unifesp), Sao Paulo, SP, Brazil b Centro Infantil Boldrini, Campinas, SP, Brazil c Faculdade de Ciencias Medicas, Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil d Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), Sao Paulo, SP, Brazil e Hospital Samaritano, Sao Paulo, SP, Brazil f Centro de Hematologia de Sao Paulo (CHSP), Sao Paulo, SP, Brazil

Thalassemia major phenotype caused by HB Zürich-Albisrieden [α2 59(E8) Gly > Arg (HBA2:C.178G > C)] in a Brazilian child

Hemoglobin (Hb) Zürich‐Albisrieden (ZA) [α2 59(E8) Gly > Arg; HBA2:c.178G > C] is a rare and highly unstable α‐chain variant. A few simple and compound heterozygotes (αZAα/αα and –/αZAα, respectively) have been described so far in Switzerland and China. We describe here a case of homozygosity for the Hb ZA mutation (αZAα/αZAα) in a Brazilian child with severe congenital hemolytic anemia and ineffective erythropoiesis.