Sandra Regina Loggetto

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.

Incidence and risk factors of aplastic anemia in Latin American countries: the LATIN case-control study

Associations between aplastic anemia and numerous drugs, pesticides and chemicals have been reported. This study conducted in Latin American countries shows a low incidence of aplastic anemia in this region of the world. Frequent exposure to benzene-based products increases this risk, while any association with specific drugs is uncertain. Background Associations between aplastic anemia and numerous drugs, pesticides and chemicals have been reported. However, at least 50% of the etiology of aplastic anemia remains unexplained. Design and Methods This was a case-control, multicenter, multinational study, designed to identify risk factors for agranulocytosis and aplastic anemia. The cases were patients with diagnosis of aplastic anemia confirmed through biopsy or bone marrow aspiration, selected through an active search of clinical laboratories, hematology clinics and medical records. The controls did not have either aplastic anemia or chronic diseases. A total of 224 patients with aplastic anemia were included in the study, each case was paired with four controls, according to sex, age group, and hospital where the case was first seen. Information was collected on demographic data, medical history, laboratory tests, medications, and other potential risk factors prior to diagnosis. Results The incidence of aplastic anemia was 1.6 cases per million per year. Higher rates of benzene exposure (≥30 exposures per year) were associated with a greater risk of aplastic anemia (odds ratio, OR: 4.2; 95% confidence interval, CI: 1.82–9.82). Individuals exposed to chloramphenicol in the previous year had an adjusted OR for aplastic anemia of 8.7 (CI: 0.87–87.93) and those exposed to azithromycin had an adjusted OR of 11.02 (CI 1.14–108.02). Conclusions The incidence of aplastic anemia in Latin America countries is low. Although the research study centers had a high coverage of health services, the underreporting of cases of aplastic anemia in selected regions can be discussed. Frequent exposure to benzene-based products increases the risk for aplastic anemia. Few associations with specific drugs were found, and it is likely that some of these were due to chance alone.

Incidence of aplastic anemia and agranulocytosis in Latin America: the LATIN study

CONTEXT AND OBJECTIVE Aplastic anemia and agranulocytosis are rare but life-threatening disorders, often caused by drugs and other environmental exposures. Reported incidence of these diseases seems to vary between different geographic regions, and few data on their incidence are available for Latin American countries. The aim of this work is to determine the incidence of agranulocytosis and aplastic anemia in Brazil. DESIGN AND SETTING Incidence study. Seven centers took part in the pilot phase, so as to represent all Brazilian regions. METHODS Each center conducted an active search for new cases in a defined region by means of regular contacts with all hematologists, main clinical laboratories and clinicians in hospitals of the region. RESULTS 74 patients with aplastic anemia and 16 with agranulocytosis were identified. Patients with agranulocytosis had a median age of 31 years (interquartile range, IQR: 12.5-48.2); 32.2% were male and 81.2% were white. The median age of aplastic anemia patients was 21 years (IQR 15.0-35.2); 62.2% were male, 50.0% were white and 39.2% mulatto. The incidence of agranulocytosis was estimated to be 0.5 cases per million individuals per year, ranging from 0.0 to 1.1 cases per million per year between regions. The incidence of aplastic anemia was 2.7 cases per million per year, ranging from 1.1 to 7.1 cases per million per year between regions. CONCLUSIONS Aplastic anemia and agranulocytosis are rare diseases in Brazil. However, there is considerable variability in their incidences between different regions.

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.

Helicobacter pylori infection & immune thrombocytopenic purpura in children and adolescents: A randomized controlled trial.

Abstract Helicobacter pylori and immune thrombocytopenic purpura (ITP) association is not well established in chronic ITP (cITP) in children, although the cure of thrombocytopenia in approximately half of H. pylori eradicated adult patients has been described. The aim of this study was to investigate the effect of H. pylori eradication on platelet (PLT) recovery in cITP children and adolescents through a randomized, controlled trial. A total of 85 children (mean age 11.4 years) with cITP were prospectively enrolled. Diagnosis of H. pylori was established by two locally validated tests, 13C-urea breath test and monoclonal stool antigen test. Twenty-two infected patients were identified, and randomly allocated into two groups: H. pylori treatment group (n = 11) and the non-intervention control group (n = 11). The control group was offered treatment if the thrombocytopenia persisted after the follow-up. At baseline, there were no differences regarding age, sex, duration of disease, and PLT count between groups. Sixty three of 85 patients were uninfected. PLT response was classified as complete response: PLT > 150 × 109 l−1; partial response: PLT 50–150 × 109 l−1, or an increase of 20–30 × 109 l−1; no response: PLT < 50 × 109 l−1 or an increase of <20 × 109 l−1 after at least 6 months of follow-up. Complete response was observed in 60.0% (6/10, one excluded) H. pylori eradicated patients vs. 18.2% (2/11) in non-eradicated patients (p = 0.08; OR = 6.75) after 6–9 months of follow-up. Among uninfected patients, only 13.8% (8/58) presented complete response. Two non-treated controls were treated after 6–12 months of follow-up, and PLT response was observed in 61.5% (8/13) of H. pylori eradicated patients, and in 19.0% (11/58) of uninfected patients (p = 0.004). Cytotoxin associated gene A and vacuolating cytotoxin gene A IgG antibodies were present in almost all infected patients. Therefore, the study suggests that H. pylori eradication plays a role in the management of H. pylori infected cITP children and adolescents.

Sickle cell anemia: clinical diversity and beta S-globin haplotypes.

probably as a consequence of the domestic slave trade and subsequent internal migrations from other regions of Brazil.Fetal hemoglobin (Hb F) is related to the haplotype and correlates with the clinical course of SCA. SEN and ARAB haplotypes produce the highest levels of Hb F and are associated with fewer clinical manifestations of SCA and with a lower occurrence of organ damage. BEN and CAM haplotypes exhibit intermediate levels of Hb F and clinical severity. However, the CAR haplotype is associated with lowest levels of Hb F and consequently with the worst clinical severity including a three-fold risk to develop stroke, renal failure, chronic lung disease with cor pulmonale, leg ulcers, and young adult death. The risk of acute chest syndrome (ACS), pain crises and infections is similar in individuals with the BEN or CAR haplotypes. In the USA, it has been reported that co-inheritance with the alpha-thalassemia gene has little influence in acute events during childhood

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.

Guidelines on Beta-thalassemia major - regular blood transfusion therapy: Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular: project guidelines: Associação Médica Brasileira - 2016

he guidelines project is a joint initiative of the Associação édica Brasileira and the Conselho Federal de Medicina. It aims o bring together information in medicine to standardize onduct in order to help decision-making during treatment. he data contained in this article were prepared by and re recommended by the Associação Brasileira de Hematologia, emoterapia e Terapia Celular (ABHH). Even so, all possible conucts should be evaluated by the physician responsible for

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