RESUMO
Sickle cell disease (SCD) comprises inherited red blood cell disorders due to a mutation in the ß-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 ß-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. SCD is considered a global health problem, and its incidence has increased in some areas of the world, particularly the Americas and Africa. Management of the disease varies according to the region of the world, mainly due to local resources and socioeconomic status. This review aimed to describe more recent data on SCD regarding available treatment options, especially in Brazil. New treatment options are expected to be available to all patients, particularly crizanlizumab, which is already approved in the country.
RESUMO
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. The aim of this narrative review is to describe some of the more recent data in the SCD literature regarding pathophysiology and novel treatments.
Assuntos
Anemia Falciforme , Hemoglobina Falciforme , Humanos , Anemia Falciforme/tratamento farmacológico , Eritrócitos , Hemoglobinas , Eritrócitos AnormaisRESUMO
BACKGROUND: The up-regulation of P-selectin in endothelial cells and platelets contributes to the cell-cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell-related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease. METHODS: In this double-blind, randomized, placebo-controlled, phase 2 trial, we assigned patients to receive low-dose crizanlizumab (2.5 mg per kilogram of body weight), high-dose crizanlizumab (5.0 mg per kilogram), or placebo, administered intravenously 14 times over a period of 52 weeks. Patients who were receiving concomitant hydroxyurea as well as those not receiving hydroxyurea were included in the study. The primary end point was the annual rate of sickle cell-related pain crises with high-dose crizanlizumab versus placebo. The annual rate of days hospitalized, the times to first and second crises, annual rates of uncomplicated crises (defined as crises other than the acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism) and the acute chest syndrome, and patient-reported outcomes were also assessed. RESULTS: A total of 198 patients underwent randomization at 60 sites. The median rate of crises per year was 1.63 with high-dose crizanlizumab versus 2.98 with placebo (indicating a 45.3% lower rate with high-dose crizanlizumab, P=0.01). The median time to the first crisis was significantly longer with high-dose crizanlizumab than with placebo (4.07 vs. 1.38 months, P=0.001), as was the median time to the second crisis (10.32 vs. 5.09 months, P=0.02). The median rate of uncomplicated crises per year was 1.08 with high-dose crizanlizumab, as compared with 2.91 with placebo (indicating a 62.9% lower rate with high-dose crizanlizumab, P=0.02). Adverse events that occurred in 10% or more of the patients in either active-treatment group and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain. CONCLUSIONS: In patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crises than placebo and was associated with a low incidence of adverse events. (Funded by Selexys Pharmaceuticals and others; SUSTAIN ClinicalTrials.gov number, NCT01895361 .).
Assuntos
Anemia Falciforme/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Selectina-P/antagonistas & inibidores , Dor/prevenção & controle , Adolescente , Adulto , Anemia Falciforme/complicações , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hidroxiureia/uso terapêutico , Masculino , Pessoa de Meia-Idade , Selectina-P/imunologia , Dor/etiologia , Qualidade de Vida , Adulto JovemRESUMO
BACKGROUND: Five main genes are associated with hemochromatosis; however, current studies show that, in addition to these genes, others may be associated with primary iron overload (IO). One of these is the bone morphogenetic protein 6 (BMP6), which encodes a protein that modulates hepcidin synthesis and, consequently, iron homeostasis. AIM: To identify BMP6 gene pathogenic variants in patients with IO and non-homozygous genotype for the HFE p.Cys282Tyr mutation. MATERIALS AND METHODS: Fifty-three patients with primary IO and non-homozygous genotype for the HFE p.Cys282Tyr were selected. Subsequent bidirectional DNA sequencing of BMP6 exons was performed. RESULTS: Two novel variants were found. One at homozygous state p.Gln158Ter (c.472C>T) was pathogenic, the other one at heterozygous state p.Val394Met (c.1180G>A) was of uncertain significance (VUS); the third variant at heterozygous state p.Arg257His (c.770G>A) has already been described and associated with IO. No BMP6 pathogenic variants that would explain iron overload phenotypes were detected in 94% of the studied patients. CONCLUSION: Identification of the BMP6 pathogenic variants in Brazilian patients with primary IO might contribute to the genetic understanding of this phenotype.
Assuntos
Proteína Morfogenética Óssea 6/genética , Sobrecarga de Ferro/genética , Mutação Puntual , Adulto , Feminino , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The cell adhesion molecule P-selectin plays a key role in the pathogenesis of a vaso-occlusive crisis (VOC) in patients with sickle cell disease (SCD). In the double-blind, placebo-controlled phase 2 SUSTAIN study, crizanlizumab (humanized, anti-P-selectin monoclonal antibody) 5 mg/kg significantly lowered the rate of VOC in patients with SCD by 45% vs placebo. In SUSTAIN, patients with SCD were randomized to crizanlizumab 2.5 mg/kg, crizanlizumab 5 mg/kg, or placebo intravenously 14 times over 52 weeks. The primary endpoint was the annual rate of VOC with crizanlizumab vs placebo. This post hoc descriptive analysis evaluated the proportion of patients who did not experience a VOC during the study in the following subgroups: VOCs in the year prior to study entry (2-4/5-10), SCD genotype (HbSS/non-HbSS), and concomitant hydroxyurea use (yes/no). More patients were VOC event-free in the crizanlizumab 5 mg/kg arm than in the placebo arm, including those with more frequent prior VOCs (ie, 5-10; 28.0% vs 4.2%), the HbSS genotype (31.9% vs 17.0%) and/or using concomitant hydroxyurea (33.3% vs 17.5%). Further analyses of secondary endpoints demonstrated that crizanlizumab treatment significantly increased time-to-first VOC vs placebo in these subgroups. The rates of treatment-emergent adverse events were similar between treatment arms across all subgroups. This post hoc analysis of SUSTAIN shows that in patients with a high number of prior VOCs, on concomitant hydroxyurea and/or with the HbSS genotype, crizanlizumab treatment increases the likelihood of patients being VOC event-free and delays time-to-first VOC.
Assuntos
Anemia Falciforme/complicações , Anticorpos Monoclonais/uso terapêutico , Selectina-P/antagonistas & inibidores , Dor/tratamento farmacológico , Adolescente , Adulto , Idoso , Anemia Falciforme/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antidrepanocíticos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Intervalo Livre de Progressão , Adulto JovemRESUMO
BACKGROUND: Hereditary hemochromatosis (HH) encompasses a group of autosomal recessive disorders mainly characterized by enhanced intestinal absorption of iron and its accumulation in parenchymal organs. HH diagnosis is based on iron biochemical and magnetic resonance imaging (MRI) assessment, and genetic testing. Questionnaires, such as SF-36 (short form health survey), have been increasingly used to assess the impact of diseases on the patient's quality of life (QL). In addition, different genotypes are identified as results of genetic tests in patients with suspected primary iron overload. In the present study, our aim was to evaluate whether domains of QL are different according to genotypic groups in patients suspected of HH. METHODS: Seventy-nine patients with primary iron overload were included and two genotypic groups were formed (group 1: homozygous genotype for the HFE p.Cys282Tyr mutation; group 2: other genotypes). RESULTS: Group 1 had higher means of plasma transferrin saturation (86 ± 19%) and serum ferritin (1669 ± 1209 ng/mL) compared to group 2 (71 ± 12%, 1252 ± 750 ng/mL, respectively; p = 0.001). Four domains were significantly different among groups 1 and 2: physical functioning (p = 0.03), bodily pain (p = 0.03), vitality (p = 0.02) and social functioning (p = 0.01). CONCLUSIONS: Our main finding was that patients with p.Cys282Tyr homozygosity had a worse QL scenario assessed by SF-36, compared with patients with iron overload without the same genotype. Being aware of this relationship between genotypes and QL might be helpful in the overall management of patients suspected of hereditary hemochromatosis.
Assuntos
Predisposição Genética para Doença , Hemocromatose/diagnóstico , Hemocromatose/genética , Qualidade de Vida , Adulto , Feminino , Ferritinas/sangue , Testes Genéticos , Genótipo , Homozigoto , Humanos , Ferro/sangue , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/genética , Masculino , Pessoa de Meia-Idade , Mutação , Fatores Socioeconômicos , Inquéritos e Questionários , Transferrina/metabolismoRESUMO
BACKGROUND: Pulmonary hypertension (PH) at rest is a risk factor for death in patients with sickle cell anemia (SCA). Exercise echocardiography (EE) can detect latent PH. We sought to investigate the occurrence of exercise-induced abnormal response of systolic pulmonary artery pressure (SPAP) in adult patients with SCA and normal SPAP at rest, and to identify the independent predictors of this abnormal response. METHODS AND RESULTS: Forty-four adult patients with SCA and normal SPAP at rest (tricuspid regurgitant jet flow velocity [TRV] <2.5 m/sec) were studied and divided into 2 groups: exhibiting normal SPAP after treadmill EE (TRV ≤ 2.7 m/sec) (G1), and exhibiting abnormal exercise-induced increase of SPAP (TRV > 2.7 m/sec) (G2). TRV cutoff points at rest and during EE were based on data from healthy-matched control subjects. Abnormal response of SPAP with exercise occurred in 57% of the sample (G2), with mean TRV level of 3.39 ± 0.41 m/sec (range 2.8-4.5 m/sec), significantly higher than those of G1 (2.29 ± 0.25 m/sec, range 2.0-2.7 m/sec; P < 0.001). Multivariate analysis identified TRV value in resting conditions ≥2.25 m/sec (P < 0.05), left atrial volume index ≥41 mL/m2 (P < 0.05), and a E/e'-waves ratio ≥6.3 (P < 0.05) as independent predictors of exercise-induced increase of SPAP. CONCLUSION: We concluded that adult patients with SCA and normal SPAP at rest may exhibit abnormal exercise-induced increase in SPAP, which was independently related to resting TRV levels, and indices of diastolic impairment and left ventricular filling pressure.
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Anemia Falciforme/complicações , Ecocardiografia sob Estresse/métodos , Exercício Físico/fisiologia , Hipertensão Pulmonar/etiologia , Artéria Pulmonar/fisiopatologia , Adolescente , Adulto , Anemia Falciforme/fisiopatologia , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/diagnóstico por imagem , Adulto JovemRESUMO
Sickle cell anemia (SCA), a disorder characterized by both acute and chronic inflammation, exhibits substantial phenotypic variability. Interleukin-1 beta (IL-1ß) and IL-6 are important in acute and chronic diseases, and their single nucleotide polymorphisms (SNPs) have been considered as predictors of prognosis in several inflammatory conditions. This study aims at exploring possible association of IL-1ß and IL-6 SNPs as potential genetic modifiers and or predictors of SCA clinical and laboratory phenotypes. This cross-sectional study involved 107 SCA patients and 110 age, sex and ethnicity-matched healthy individuals. The SNPs were identified by PCR-RFLP for IL-1ß (-511C>T and +3954C>T) and IL-6 (-597G>A and -174G>C) genes. Associations between these SNPs and the clinical and laboratory profiles of patients with SCA were then determined. Allelic and genotypic frequencies of IL-1ß and IL-6 SNPs between patients with SCA and controls were similar and followed HWE. IL-1ß +3954C>T SNP was associated with increased risk of osteonecrosis, elevated pulmonary arterial pressure and lower absolute reticulocyte count, while IL-6 -597G>A was associated with higher likelihood of retinopathy and leg ulcer. These data indicate that IL-1ß and IL-6 gene SNPs are associated with SCA complications among Brazilian patients and may act as genetic predictors of SCA clinical heterogeneity.
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Anemia Falciforme/genética , Interleucina-1beta/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Brasil/epidemiologia , Estudos Transversais , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
This open-label, prospective, phase 2 study evaluated the safety and efficacy of deferasirox (10 ± 5 mg/kg/d) in patients with hereditary hemochromatosis (HH) and iron overload refractory to or intolerant of phlebotomy. Ten patients were enrolled and all completed the 12-month treatment period. There were significant decreases from baseline to end of study (i.e., 12 months) in median serum ferritin (P < 0.001), mean transferrin saturation (P < 0.05), median liver iron concentration (P < 0.001), and mean alanine aminotransferase (P < 0.05). The median time to achieve serum ferritin reduction ≥50% compared to baseline was 7.53 months. The most common adverse events were mild, transient diarrhea (n = 5) and nausea (n = 2). No patient experienced an increase in serum creatinine that exceeded the upper limit of normal. These data confirm that deferasirox was well tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients.
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Benzoatos/uso terapêutico , Hemocromatose/complicações , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Triazóis/uso terapêutico , Adulto , Idoso , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Biomarcadores , Deferasirox , Índices de Eritrócitos , Feminino , Hemocromatose/diagnóstico , Hemocromatose/genética , Proteína da Hemocromatose , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/diagnóstico , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Fatores de Tempo , Resultado do Tratamento , Triazóis/administração & dosagem , Triazóis/efeitos adversosRESUMO
Body iron disorders have been reported after myeloablative conditioning in patients undergoing hematopoietic stem cell transplantation (HSCT). There is a concern that labile plasma iron (LPI), the redox-active form of iron, can be involved in the occurrence of toxicity and other complications commonly observed in the early post-HSCT period. In order to better understand the LPI kinetics and its determinants and implications, we undertook sequential LPI determinations before and after conditioning until engraftment in 25 auto-HSCT patients. Increased LPI was present in only 5 patients before starting conditioning. Shortly after conditioning, LPI levels were increased in 23 patients, with peak at day 0, returning to normal range upon engraftment in 21 patients. Overall, LPI levels correlated weakly with serum ferritin and more strongly with transferrin saturation; however, both parameters were apparently not applicable as surrogate markers for increased LPI. Although this was a small cohort, logistic regression suggested that baseline LPI levels could predict occurrence of grade III or IV toxicity. In conclusion, LPI kinetics is influenced by aplasia following conditioning and engraftment. Measuring LPI before starting conditioning can offer an opportunity to predict toxicity and, perhaps, the need for chelation therapy.
Assuntos
Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sobrecarga de Ferro/etiologia , Ferro/sangue , Condicionamento Pré-Transplante/efeitos adversos , Adulto , Idoso , Antioxidantes/química , Ácido Ascórbico/química , Estudos de Coortes , Deferiprona , Feminino , Corantes Fluorescentes/química , Seguimentos , Humanos , Ferro/química , Quelantes de Ferro/química , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Piridonas/química , Rodaminas/química , Índice de Gravidade de Doença , Adulto JovemRESUMO
INTRODUCTION: Sickle cell disease (SCD) is an inherited and multisystem blood disorder characterized by hemolytic anemia, vaso-occlusive crises (VOCs), progressive multiorgan damage and increased mortality. In Brazil, it is one of the most common monogenic diseases afflicting 60,000 to 100,000 individuals, however, there are sparse epidemiological data, as well as information on the utilization of public healthcare resources. METHOD: This was a 5-year (2016 - 2020) retrospective study conducted at one Brazilian reference center on SCD - Santa Casa de Sao Paulo, in Sao Paulo, Brazil. RESULTS: Among a total of 100 eligible adult patients, the median age was 31.0 years old, 84% of the patients were aged between 18 and 45 years old; 59% were women and 91% presented the genotype HbSS. The number of hematologist and non-hematologist visits at the outpatient unit were 2,198 and 1,436, respectively. The number of hospital ER visits was 758, of which 51% required 864 days of hospitalization. The main cause for seeking hospital medical care was the VOCs. The numbers and ratios of VOCs were: 1 to 10 VOCs, 64%; 11 to 20, 15%, and; 21 or more, 1%. There was a statistically significant difference between the number of VOCs and hospitalizations, as well as infection. CONCLUSION: Results indicate the burden of SCD on Brazilian patients' daily lives, the impact of VOCs on public healthcare resources, the importance of having a national surveillance program to improve resource utilization and clinical outcomes of patients with SCD and the urgent need for the revitalizing of the current national comprehensive SCD care programs.
RESUMO
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. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.
RESUMO
Sickle cell disease (SCD) is a group of hereditary chronic diseases with a substantial impact on quality of life and morbimortality. In Brazil, it is 1 of the most common hereditary diseases; however, there are sparse epidemiological data for the country. Using data from death certificates, we aimed to estimate the median age at death, years of life lost because of SCD, and the median survival. From 2015 to 2019, we identified 3320 records of deaths of individuals with SCD, from a total of 6 553 132 death records. Among individuals with SCD, the median age at death was 37 years less than that of the general population (SCD: aged 32.0 years at death, interquartile range [IQR], 19.0-46.0; general population: aged 69.0 years at death; IQR, 53.0-81.0). Results were consistent when stratified by sex or race. Over the 5 years evaluated, crude death rates varied from 0.30 to 0.34 per 100 000 inhabitants (mean 0.32 per 100 000 inhabitants). We estimated a prevalence of 60 017 individuals living with SCD (29.02 cases per 100 000) and an average incidence of 1362 cases yearly. The median estimated survival was 40 years for individuals with SCD and 80 years for the general population. SCD was associated with an increased risk of mortality in most age ranges. Among individuals with SCD aged between 1 and 9 years and between 10 and 39 years, the risk of death was 32 and 13 times higher, respectively. The most common causes of death were sepsis and respiratory failure. These results highlight the burden of SCD in Brazil and the necessity of improved care for this population.
Assuntos
Anemia Falciforme , Qualidade de Vida , Humanos , Lactente , Pré-Escolar , Criança , Brasil/epidemiologia , Anemia Falciforme/complicações , Incidência , PrevalênciaRESUMO
PURPOSE: We assessed penile rigidity during sleep and the relationship of sleep abnormalities with priapism in adults with sickle cell disease. MATERIALS AND METHODS: This was a case-control study of 18 patients with sickle cell disease and a history of priapism during the previous year, and 16 controls with sickle cell disease. Participants underwent overnight polysomnography and RigiScan® Plus recording to detect penile rigidity oscillations. RESULTS: The priapism group (cases) showed a higher apnea-hypopnea index and oxyhemoglobin desaturation parameters than controls. A lower positive correlation between the apnea-hypopnea index and oxyhemoglobin desaturation time was observed in cases than in controls (Spearman coefficient ρ = 0.49, p = 0.05 vs ρ = 0.76, p <0.01), suggesting that desaturation events occurred independently of apnea. Two controls and 14 cases had a total sleep time that was greater than 10% with oxyhemoglobin saturation less than 90% but without CO(2) retention. Penile rigidity events were observed during rapid eye movement sleep and during stage 2 of nonrapid eye movement sleep, particularly in cases. The duration of penile rigidity events concomitant to respiratory events was higher in cases than in controls. Regression analysis revealed that the periodic limb movement and desaturation indexes were associated with priapism after adjusting for rapid eye movement sleep and lung involvement. Finally, oxyhemoglobin saturation less than 90% was associated with priapism after adjusting for lung involvement, hyperhemolysis and the apnea-hypopnea index. CONCLUSIONS: Oxyhemoglobin desaturation during sleep was associated with priapism history. It may underlie the distribution pattern of penile rigidity events during sleep in these patients.
Assuntos
Anemia Falciforme/complicações , Hipóxia/complicações , Priapismo/etiologia , Síndromes da Apneia do Sono/complicações , Adolescente , Adulto , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
To evaluate, in a longitudinal study, the profile of lipid peroxidation and antioxidant capacity markers in sickle cell anaemia patients receiving different treatments and medication over different time periods. The three groups were: patients undergoing transfusion therapy and receiving iron chelator deferasirox (DFX group, n = 20); patients receiving deferasirox and hydroxyurea (DFX + HU group, n = 10), and patients receiving only folic acid (FA group, n = 15). Thiobarbituric acid-reactive substance (TBARS) assays and trolox-equivalent antioxidant capacity (TEAC) assays were evaluated during two different periods of analysis, T0 and T1 (after ~388 days). Higher FA group TBARS values were observed compared with the DFX + HU group (p = 0.016) at T0; and at T1, higher FA group TBARS values were also observed compared with both the DFX group (p = 0.003) and the DFX + HU group (p = 0.0002). No variation in TEAC values was seen between groups, at either T0 or T1. The mean values of TBARS and TEAC for both the DFX and DFX + HU groups decreased at T1. The antioxidant effects of HU and DFX were observed by through an increase in TEAC levels in DFX and DFX + HU groups when compared with those of normal subjects. Increased TEAC values were not recorded in the FA group, and lipid peroxidation was seen to decrease after DFX and HU use.
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Anemia Falciforme/tratamento farmacológico , Antioxidantes/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Adolescente , Adulto , Anemia Falciforme/fisiopatologia , Antioxidantes/farmacologia , Benzoatos/farmacologia , Benzoatos/uso terapêutico , Biomarcadores/metabolismo , Transfusão de Sangue , Criança , Deferasirox , Feminino , Humanos , Quelantes de Ferro/farmacologia , Quelantes de Ferro/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Triazóis/farmacologia , Triazóis/uso terapêutico , Adulto JovemRESUMO
The efficacy and safety of a 2-year treatment with deferasirox was evaluated in 31 patients with sickle cell anemia and transfusional iron overload. At 24 months, there were significant decreases from baseline in mean serum ferritin (from 2,344.6 to 1,986.3 µg/l; p = 0.040) and in mean liver iron concentration (from 13.0 ± 5.4 to 9.3 ± 5.7 mg Fe/g dry weight; p < 0.001). Myocardial T2* values were normal (>20 ms) in all patients at baseline and did not change significantly over the course of the study. However, there was a significant improvement from baseline in left ventricular ejection fraction at 24 months (62.2-64.6%; p = 0.02). Deferasirox was generally well tolerated with no progressive increases in serum creatinine or renal failure observed. These data confirm that deferasirox is effective in reducing body iron burden in patients with sickle cell anemia and transfusional iron overload.
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Anemia Falciforme/tratamento farmacológico , Benzoatos/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Triazóis/uso terapêutico , Adolescente , Adulto , Benzoatos/efeitos adversos , Deferasirox , Feminino , Humanos , Quelantes de Ferro/efeitos adversos , Masculino , Estudos Prospectivos , Triazóis/efeitos adversos , Adulto JovemRESUMO
Hemochromatosis is currently characterized by the iron overload caused by hepcidin deficiency. Large advances in the knowledge on the hemochromatosis pathophysiology have occurred due to a better understanding of the protein of the iron metabolism, the genetic basis of hemochromatosis and of other iron overload diseases or conditions which can lead to this phenotype. In the present review, the main aims are to show updates on hemochromatosis and to report a practical set of therapeutic recommendations for the human factors engineering protein (HFE) hemochromatosis for the p.Cys282Tyr (C282Y/C282Y) homozygous genotype, elaborated by the Haemochromatosis International Taskforce.
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Hereditary hyperferritinemia-cataract syndrome is a rare autosomal dominant disease caused by a genetic mutation in the iron responsive element in the 5' untranslated region of the ferritin light chain gene. Hereditary hyperferritinemia-cataract syndrome is characterized by elevated serum ferritin levels and bilateral cataract development early in life and may be misdiagnosed as hemochromatosis. This case report describes a Brazilian family with a clinical diagnosis of hereditary hyperferritinemia-cataract syndrome, which was submitted to ferritin light chain gene sequencing. The genetic mutation c.-164C>G was identified in the 5' untranslated region. In conclusion, genetic testing can be used for accurate diagnosis of hereditary hyperferritinemia-cataract syndrome to avoid misdiagnosis of hemochromatosis, other diseases associated with iron overload or ophthalmic diseases.
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Catarata , Hemocromatose , Humanos , Apoferritinas/genética , Hemocromatose/genética , Regiões 5' não Traduzidas , Brasil , Catarata/diagnóstico , Catarata/genética , Ferro , LinhagemRESUMO
INTRODUCTION: The aim of this study was to describe maternal and perinatal outcomes in pregnant women with sickle cell disease (SCD) followed at Santa Casa de Sao Paulo over a 10-year period (between 2010 and 2019). METHOD: Fifty-five records of pregnancies were analyzed among 35 women with SCD. RESULTS: Among 29 newborns, 19 (65.5%) were full-term and 10 pre-term; 24 (82.7%) caesareans and 5 (17.2%) natural births were observed. The mean gestational age at birth and mother`s age were 36.6 weeks (30-40) and 26.7 years (17-39), respectively. No maternal death was observed. The main maternal obstetric and non-obstetric complications were: pre-eclampsia and gestational diabetes, and vaso-occlusive crisis, urinary tract infection and acute chest syndrome, respectively. Twenty-six (47.0%) fetal deaths were observed, 24 being intrauterine fetal (14 early abortions, 10 late abortions and 2 stillbirths). Regarding the red blood cell transfusion history, 40 (72.7%) out of 55 pregnancies received transfusion. Pregnant women who received 6 or more transfusions throughout pregnancy had a significantly lower number of abortions, i.e., no cases of early abortion and only 1 case of late abortion, versus 14 and 9 cases in pregnancies with 0-5 transfusions, respectively. Despite advances in the management of SCD, pregnant women with SCD (particularly those with HbSS) are at a high risk for maternal and fetal complications, even though they are followed in reference centers. CONCLUSION: The lower risk of intrauterine fetal death for those women who received more transfusions throughout pregnancy observed in the current study leads us once more to raise the need for prospective, multicenter, randomized trials to determine whether the potential benefits balance the risks of prophylactic transfusions.
RESUMO
BACKGROUND: Hemochromatosis is a genetic condition of iron overload caused by deficiency of hepcidin. In a previous stage of this study, patients with suspected hemochromatosis had their quality of life (QL) measured. We observed that QL scores differed among genotypic groups of patients. In this reported final phase of the study, the aims were to compare QL scores after a treatment period of approximately 3 years and to analyze a possible association of the serum ferritin values with QL scores. METHODS: Sixty-five patients were enrolled in this final phase and divided into group 1 (patients that showed primary iron overload and homozygous genotype for the HFE p.Cys282Tyr mutation) and group 2 (other kinds of genotypes). Short Form 36 (SF-36) was performed and consisted of eight domains with a physical and also a mental component. RESULTS: Both groups had a significant decrease in serum ferritin concentrations: group 1 had a variation from 1844 ± 1313 ng/mL to 281 ± 294 ng/mL, and group 2 had a variation from 1216 ± 631 ng/mL to 236 ± 174 ng/mL. Group 1 had a smaller mean value for these six SF-36 domains compared with group 2, indicating a worse QL. CONCLUSIONS: In this final stage, six domains demonstrated a difference among genotypic groups (role emotional and mental health, adding to the four of the initial phase), reassuring the impact of the identified genotype on the QL of hemochromatosis patients. Furthermore, despite that both patient groups demonstrated similar and significant decreases in serum ferritin values, no association was found between the decrease in this biological parameter and the SF-36 domains.