Sickle Cell Disease in Brazil: Current Management.

Sickle cell disease (SCD) comprises inherited red blood cell disorders due to a mutation in the β-globin gene (c20A > T, pGlu6Val) and is characterized by the presence of abnormal hemoglobin, hemoglobin S, hemolysis, and vaso-occlusion. This mutation, either in a homozygous configuration or in compound states with other β-globin mutations, leads to polymerization of hemoglobin S in deoxygenated conditions, causing modifications in red blood cell shape, particularly sickling. Vaso-occlusive crisis (VOC) is the hallmark of the disease, but other severe complications may arise from repeated bouts of VOCs.

Consensus of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) and the Brazilian Ministry of Health - General management of blood and blood products on the tests necessary for the release of exceptional medicines for sickle cell disease.

To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea.

Novel Insights into the Pathophysiology and Treatment of Sickle Cell Disease.

The polymerization of hemoglobin under deoxygenation is the main pathophysiological event in sickle cell diseases, described more than 70 years ago. The last two decades have seen a major increase in knowledge about the cascade of events that follow the polymerization of hemoglobin and the ensuing sickling of red blood cells. Several distinctive therapeutic targets have been discovered as a result, and a few drugs with innovative mechanisms of action are already on the market, while several others are the focus of ongoing trials.

Factors related to the readiness of Brazilian chronic pediatric patients to transition to care in adult clinics.

Objective: Advances in medicine have increased the life expectancy of pediatric patients with chronic illnesses, and challenges with the guided transition of adolescents and young adults from pediatric clinics to adult clinics have grown. The aim of this study was to better understand readiness and factors related to this transition process in Brazil.

Method: In this cross-sectional study of 308 patients aged from 16 to 21 years under follow-up in pediatric specialties, the degree of readiness for transition was assessed using the Transition Readiness Assessment Questionnaire (TRAQ) and its domains.

Zinc in sickle cell disease: A narrative review.

Sickle cell disease (SCD) is an inherited disease caused by hemoglobin S mutated hemoglobin S. It is characterized by chronic hemolysis, intermittent vaso-occlusive crises followed by ischemia-reperfusion, and organ damage. These patients have an increased risk of multiple micronutrient deficiencies, such as zinc.

Sickle cell anemia: hierarchical cluster analysis and clinical profile in a cohort in Brazil.

Introduction: Sickle cell anemia is a monogenic disorder caused by a mutation in the β-hemoglobin gene, resulting in sickle hemoglobin that can polymerize. Presentation and clinical course have significant inter-individual variability and classifying these patients for severity is a challenge.

Methods: We applied hierarchical clusters with 10 routine laboratory tests to understand if this grouping could be associated with clinical manifestations.

miRNA profile and disease severity in patients with sickle cell anemia.

Identification of biomarkers associated with severity in sickle cell anemia is desirable. Circulating serum microRNAs (miRNA) are targets studied as diagnostic or prognostic markers, but few studies have been conducted in sickle cell anemia. The purpose of this study is to identify specific signatures of miRNAs in plasma samples from sickle cell anemia patients according to severity indexes.

Genetic contribution and functional impairment of inflammasome in sickle cell disease.

Background: Sickle cell disease (SCD), one of the most common single-gene disorders, is caused by mutations in the hemoglobin ß-chain gene. Clinical presentation is heterogeneous, and inflammation is a common condition. Thereby, we hypothesized that inflammasome and related cytokine IL-1ß could represent significant SCD pathogenesis contributors.

Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal hemoglobinuria is a chronic, multi-systemic, progressive and life-threatening disease characterized by intravascular hemolysis, thrombotic events, serious infections and bone marrow failure. Paroxysmal nocturnal hemoglobinuria results from the expansion of a clone of hematopoietic cells that due to an inactivating mutation of the X-linked gene PIG-A are deficient in glycosylphosphatidylinositol-linked proteins. Early diagnosis, using flow cytometry performed on peripheral blood, the gold standard test to confirm the diagnosis of paroxysmal nocturnal hemoglobinuria, is essential for improved patient management and prognosis.

Serum folate and cytokines in heterozygous β-thalassemia.

Introduction: Folate deficiency is commonly reported in β-thalassemia. Individuals heterozygous for β-thalassemia may have higher folate requirements than normal individuals.

Objectives: To document the concentration of serum total folate and its forms in β-thalassemia heterozygote users (β-TmU) and nonusers (β-TmN) of 5 mg folic acid/d; to determine whether folic acid (FA) consumption from fortified foods allows beta-Tm patients, who do not take FA supplements, to meet their dietary folate requirements; and to investigate the association between higher serum unmetabolized folic acid (UMFA) and inflammatory cytokine concentrations.

Male sickle cell patients, compensated transpubertal hypogonadism and normal final growth.

Objective: Investigate the gonadal hormonal function in sickle cell individuals.

Context: Sickle cell disease (SCD) is associated with delayed physical and sexual development, and it has been related to both primary testicular failure and hypothalamo-pituitary-gonadal axis abnormalities.

Design: The study of the pituitary gonadotrophin reserve was done evaluating the hormonal levels before and after stimulation by gonadoliberin.

Molecular matching for patients with haematological diseases expressing altered RHD-RHCE genotypes.

Background And Objectives: The high homology and the inverted orientation of RHD and RHCE may give rise to non-functional and aberrant RH alleles. RH genotyping is used to screen RH matched donors to African descent patients. This study aimed to define a strategy for testing RHD and RHCE variants in blood donors to provide compatible units for transfusion of patients with haematological diseases.

Daily supplementation with 5 mg of folic acid in Brazilian patients with hereditary spherocytosis.

Patients with hereditary spherocytosis (HS) have increased rates of erythropoiesis and higher folate requirements. In a case-control study of patients with HS, we evaluated the associations between the use of 5 mg folic acid (FA) daily and serum concentrations of folate, unmetabolized folic acid (UMFA), interleukin (IL)-6, IL-8, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α); and mRNA expression of (), (), , and genes. Total serum folate and folate forms were measured in 27 patients with HS (21 users [HS-U] and 6 non-users [HS-NU] of supplemental FA) and 54 healthy controls not consuming 5 mg/day supplemental FA.

Cerebral Vasoreactivity in Children with Sickle Cell Disease: A Transcranial Doppler Study.

Background: Impairment of vasodilatory capacity reflecting reduced cerebrovascular reserve was previously shown in adults with sickle cell disease (SCD) and might play a role in the pathophysiology of stroke in such patients. We examined the hypothesis that children with SCD would also have a higher frequency of impaired cerebral vasoreactivity when compared with healthy age- and gender-matched controls.

Methods: Patients were recruited from our hematology outpatient clinic.

Quality of life in adults with sickle cell disease: an integrative review of the literature.

Objective: To identify the available evidence in the literature on health-related quality of life in adults with sickle cell disease.

Method: integrative review of MEDLINE, CUMED, LILACS and SciELO databases, from articles developed in this area, published between 2005 and 2015, in English, Portuguese or Spanish.

Results: 22 articles were included, six scales were used to evaluate health-related quality of life scores: three generic and three specific.

Changes in Transcranial Doppler Flow Velocities in Children with Sickle Cell Disease: The Impact of Hydroxyurea Therapy.

Background And Objectives: Hydroxyurea (HU) was recently described as a substitute for chronic transfusion for children with sickle cell disease (SCD) and abnormal transcranial Doppler (TCD) velocities who have received at least 1 year of transfusions. However, the role of HU in reverting elevated TCD velocities in patients not treated with transfusion is still debatable. The objective of the study was to examine whether HU influences the progression of TCD velocities in children with SCD.

A phased SNP-based classification of sickle cell anemia HBB haplotypes.

Background: Sickle cell anemia causes severe complications and premature death. Five common β-globin gene cluster haplotypes are each associated with characteristic fetal hemoglobin (HbF) levels. As HbF is the major modulator of disease severity, classifying patients according to haplotype is useful.