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4.
Int J Lab Hematol ; 41 Suppl 1: 82-88, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31069977

RESUMO

Sickle cell disease has been largely an invisible global health issue, especially in regions of high incidence mainly due to lack of awareness among both the local health policy makers and the public. Public health interventions, such as screening of newborns, provision of prophylaxis against bacterial infections, and immunizations against pneumococcal infections can have the greatest impact. Family education on assessment of spleen size and subsequent detection of splenic sequestration and promptness to seek medical attention for a febrile child is also important in the control of the morbidity and mortality of children with SCD living in resource-poor countries. In addition to these affordable interventions, hydroxyurea therapy is necessary to decrease both the acute and chronic complications of sickle cell anemia. Sickle cell disease has been recognized to have global health significance by key institutions including the World Health Organization in 2006 and the United Nation is 2008. In 2010, the WHO released national health care management goals and set targets to be achieved by the countries in sub-Saharan Africa for the control and management of SCD. These are yet to be translated into action. To do, this would require active and sustainable public-private partnerships for sustainable program development in these regions. Effective interventions should be integrated into existing health systems, the best examples linking primary healthcare facilities to specialized sickle cell disease centers in regional and tertiary healthcare institutions.


Assuntos
Anemia Falciforme , Mortalidade da Criança , Efeitos Psicossociais da Doença , Assistência à Saúde , Educação de Pacientes como Assunto , África ao Sul do Saara , Anemia Falciforme/mortalidade , Anemia Falciforme/terapia , Criança , Pré-Escolar , Feminino , Humanos , Masculino
5.
Nat Med ; 25(5): 776-783, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30911135

RESUMO

Re-expression of the paralogous γ-globin genes (HBG1/2) could be a universal strategy to ameliorate the severe ß-globin disorders sickle cell disease (SCD) and ß-thalassemia by induction of fetal hemoglobin (HbF, α2γ2)1. Previously, we and others have shown that core sequences at the BCL11A erythroid enhancer are required for repression of HbF in adult-stage erythroid cells but are dispensable in non-erythroid cells2-6. CRISPR-Cas9-mediated gene modification has demonstrated variable efficiency, specificity, and persistence in hematopoietic stem cells (HSCs). Here, we demonstrate that Cas9:sgRNA ribonucleoprotein (RNP)-mediated cleavage within a GATA1 binding site at the +58 BCL11A erythroid enhancer results in highly penetrant disruption of this motif, reduction of BCL11A expression, and induction of fetal γ-globin. We optimize conditions for selection-free on-target editing in patient-derived HSCs as a nearly complete reaction lacking detectable genotoxicity or deleterious impact on stem cell function. HSCs preferentially undergo non-homologous compared with microhomology-mediated end joining repair. Erythroid progeny of edited engrafting SCD HSCs express therapeutic levels of HbF and resist sickling, while those from patients with ß-thalassemia show restored globin chain balance. Non-homologous end joining repair-based BCL11A enhancer editing approaching complete allelic disruption in HSCs is a practicable therapeutic strategy to produce durable HbF induction.


Assuntos
Edição de Genes/métodos , Células-Tronco Hematopoéticas/metabolismo , Sequência de Aminoácidos , Anemia Falciforme/sangue , Anemia Falciforme/genética , Anemia Falciforme/terapia , Sequência de Bases , Sistemas CRISPR-Cas , Proteínas de Transporte/genética , Elementos Facilitadores Genéticos , Células Precursoras Eritroides/metabolismo , Hemoglobina Fetal/biossíntese , Hemoglobina Fetal/genética , Transplante de Células-Tronco Hematopoéticas , Humanos , Mutação INDEL , Proteínas Nucleares/genética , RNA Guia/genética , Talassemia beta/sangue , Talassemia beta/genética , Talassemia beta/terapia , gama-Globinas/biossíntese , gama-Globinas/genética
6.
Transfus Apher Sci ; 58(2): 128-131, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30879904

RESUMO

Sickle cell disease (SCD) is a genetic disorder characterised by a single mutation of the beta globin gene, causing the production of an abnormal haemoglobin called sickle haemoglobin (HbS). In its deoxygenated form, HbS polymerises, causing major rheological disorders, which presents clinically as periodic vaso-occlusive crises, chronic haemolysis and chronic vascular dysfunction. Patients often resort to a background treatment, and transfusion remains the cornerstone in the management of the disease, significantly reducing morbidity and mortality. The aim of red blood cell exchange (RBCX) is to improve tissue oxygenation by increasing haemoglobin levels while lowering HbS levels. RBCX can be performed by manual or automated exchange, and each technique has its own set of advantages and disadvantages. This article will outline the transfusion indications for the main complications of SCD, as well as the most appropriate strategy to use.


Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/terapia , Transfusão de Eritrócitos/métodos , Anemia Falciforme/patologia , Humanos
7.
Transfus Apher Sci ; 58(2): 142-146, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30910616

RESUMO

Red blood cell exchange (RBCX) is a standard option for treating or preventing complications in patients with sickle cell disease (SCD). According to the patient's blood volume, the amounts of red blood cells (RBC) to be exchanged and the practices of the apheresis and clinical teams, such treatment requires numerous red blood cell units (RBCUs) (3-15 RBCUs per procedure). To perform RBCXs safely and prevent the risk of alloimmunization, appropriate RBCUs must be selected and transfused to replace the sickled RBCs. Understanding of alloimmunization in patients with SCD strengthened the development of recommendations for preventing the risk of alloimmunization. This review describes the alloimmunization risk, the methods used to decrease the risk, and our own experience.


Assuntos
Anemia Falciforme/terapia , Transfusão de Eritrócitos/métodos , Eritrócitos/metabolismo , Anemia Falciforme/patologia , Humanos
8.
Transfus Apher Sci ; 58(2): 136-141, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30914240

RESUMO

Automatic red blood cell exchange i.e. using devices (RBCX) has become a standard therapy to remove abnormal red blood cells (RBC) in adults and children affected by sickle cell disease (SCD). This treatment is performed both in emergency to treat acute complications and through a regular program of RBCX to prevent the recurrence of complications. However, small children, i.e. those with a low body weight, height and total blood volume, are at risk of relative hypovolemia and metabolic complications during the procedure. Moreover, the peripheral venous access is limited among young children, which requires alternative short- or long-term venous access. These two main limiting factors necessitate adaptations of the procedures and subsequent monitoring during and after the sessions. However, performing RBCX in children requires other adaptations and cautions that must be considered. Our review summarizes the limits, safety precautions and the adaptations of the techniques to ensure RBCX in children.


Assuntos
Anemia Falciforme/terapia , Transfusão de Eritrócitos/métodos , Adolescente , Anemia Falciforme/patologia , Criança , Pré-Escolar , Feminino , Humanos
9.
Pediatr Ann ; 48(2): e78-e85, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30747984

RESUMO

Contraception and sexual health form a key part of comprehensive health care for all adolescents, including those who suffer from chronic illness. Multiple studies have shown that adolescents with chronic illness have rates of sexual activity equal to or greater than their healthy counterparts. Primary care pediatricians have the most comprehensive view of the health of their medically complex patients and the benefit of a longstanding relationship. The Centers for Disease Control and Prevention have created a comprehensive guide that provides advice on safe contraceptive options for patients with complex medical conditions. Here we review three cases of adolescents with common chronic medical conditions: von Willebrand disease, systemic lupus erythematosus, and sickle cell disease. [Pediatr Ann. 2019;48(2):e78-e85.].


Assuntos
Doença Crônica/terapia , Anticoncepcionais/administração & dosagem , Necessidades e Demandas de Serviços de Saúde , Gravidez na Adolescência/prevenção & controle , Saúde Sexual , Adolescente , Anemia Falciforme/complicações , Anemia Falciforme/terapia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/terapia , Gravidez , Comportamento Sexual , Adulto Jovem , Doenças de von Willebrand/complicações , Doenças de von Willebrand/terapia
10.
Adv Exp Med Biol ; 1144: 37-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30715679

RESUMO

Sickle cell disease (SCD) is an inherited monogenic disorder resulting in serious mortality and morbidity worldwide. Although the disease was characterized more than a century ago, there are only two FDA approved medications to lessen disease severity, and a definitive cure available to all patients with SCD is lacking. Rapid and substantial progress in genome editing approaches have proven valuable as a curative option given plausibility to either correct the underlying mutation in patient-derived hematopoietic stem/progenitor cells (HSPCs), induce fetal hemoglobin expression to circumvent sickling of red blood cells (RBCs), or create corrected induced pluripotent stem cells (iPSCs) among other approaches. Recent discovery of CRISPR/Cas9 has not only revolutionized genome engineering but has also brought the possibility of translating these concepts into a clinically meaningful reality. Here we summarize genome engineering applications using CRISPR/Cas9, addressing challenges and future perspectives of CRISPR/Cas9 as a curative option for SCD.


Assuntos
Anemia Falciforme/terapia , Sistemas CRISPR-Cas , Edição de Genes , Hemoglobina Fetal , Células-Tronco Hematopoéticas/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia
11.
JAMA ; 321(3): 266-276, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30667500

RESUMO

Importance: In children with sickle cell anemia (SCA), high transcranial Doppler (TCD) velocities are associated with stroke risk, which is reduced by chronic transfusion. Whether matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) can reduce velocities in patients with SCA is unknown. Objective: To determine the association of MSD-HSCT with TCD velocities as a surrogate for the occurrence of ischemic stroke in children with SCA. Design, Setting, and Participants: Nonrandomized controlled intervention study conducted at 9 French centers. Patients with SCA were enrolled between December 2010 and June 2013, with 3-year follow-up ending in January 2017. Children with SCA were eligible if younger than 15 years, required chronic transfusions for persistently elevated TCD velocities, and had at least 1 sibling without SCA from the same 2 parents. Families agreed to HLA antigen typing and transplantation if a matched sibling donor was identified or to standard care in the absence of a matched sibling donor. Exposures: MSD-HSCT (n = 32), compared with standard care (n = 35) (transfusions for ≥1 year with potential switch to hydroxyurea thereafter), using propensity score matching. Main Outcomes and Measures: The primary outcome was the highest time-averaged mean of maximum velocities in 8 cerebral arteries, measured by TCD (TCD velocity) at 1 year. Twenty-five of 29 secondary outcomes were analyzed, including the highest TCD velocity at 3 years and normalization of velocities (<170 cm/s) and ferritin levels at 1 and 3 years. Results: Sixty-seven children with SCA (median age, 7.6 years; 35 girls [52%]) were enrolled (7 with stroke history). In the matched sample, highest TCD velocities at 1 year were significantly lower on average in the transplantation group (129.6 cm/s) vs the standard care group (170.4 cm/s; difference, -40.8 cm/s [95% CI, -62.9 to -18.6]; P < .001). Of the 25 analyzed secondary end points, 4 showed significant differences, including the highest TCD velocity at 3 years (112.4 cm/s in the transplantation group vs 156.7 cm/s in the standard care group; difference, -44.3 [95% CI, -71.9 to -21.1]; P = .001); normalization rate at 1 year (80.0% in the transplantation group vs 48.0% in the standard care group; difference, 32.0% [95% CI, 0.2% to 58.6%]; P = .045); and ferritin levels at 1 year (905 ng/mL in the transplantation group vs 2529 ng/mL in the standard care group; difference, -1624 [95% CI, -2370 to -879]; P < .001) and 3 years (382 ng/mL in the transplantation group vs 2170 ng/mL in the standard care group; difference, -1788 [95% CI, -2570 to -1006]; P < .001). Conclusions and Relevance: Among children with SCA requiring chronic transfusion because of persistently elevated TCD velocities, MSD-HSCT was significantly associated with lower TCD velocities at 1 year compared with standard care. Further research is warranted to assess the effects of MSD-HSCT on clinical outcomes and over longer follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT01340404.


Assuntos
Anemia Falciforme/terapia , Circulação Cerebrovascular/fisiologia , Transplante de Células-Tronco Hematopoéticas , Irmãos , Ultrassonografia Doppler Transcraniana , Aloenxertos , Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/fisiopatologia , Velocidade do Fluxo Sanguíneo , Criança , Feminino , Ferritinas/sangue , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pontuação de Propensão , Qualidade de Vida , Condicionamento Pré-Transplante
12.
Vox Sang ; 114(2): 178-181, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30695814

RESUMO

Disturbances in the physiological regulation of erythropoietin (EPO) in patients with sickle cell disease (SCD) may contribute to worsening anaemia and increased transfusion requirements, but the use of recombinant EPO in this group of patients is controversial. The objective of this study was to evaluate the use of this drug in adult patients with SCD and its effects on haemoglobin levels and transfusion requirements. We conducted a retrospective analysis at the University of Campinas, with nineteen adults with a diagnosis of SCD (HbSS and HbS/ß+ thalassaemia), who had received at least 1 year of EPO therapy between 2007 and 2014. Haemoglobin concentrations and trends of variation in transfused RBC volumes were compared before and after EPO administration. We observed that seven patients had a good response to treatment (Hb increment higher than 1·5 g/dl) and nine had a partial response (0·5-1·5 g/dl increment) and there was a significant decrease in the need for transfusion amongst those who usually required regular transfusions. There were no increases in the rates of vaso-occlusive crisis or venous thromboembolism in comparison to the year before the onset of the therapy. Erythropoietin therapy led to a marked increase in haemoglobin concentration with a concomitant decrease in the demand for transfusion. Considering all complications related to allogeneic transfusion, we believe that EPO therapy represents an important therapeutic tool in sickle cell anaemia.


Assuntos
Anemia Falciforme/tratamento farmacológico , Eritropoetina/uso terapêutico , Adulto , Anemia Falciforme/terapia , Transfusão de Eritrócitos/efeitos adversos , Eritropoetina/administração & dosagem , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico
14.
Hematology ; 24(1): 189-198, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30479187

RESUMO

OBJECTIVE: Hospital admissions are significant events in the care of individuals with sickle cell disease (SCD) due to associated costs and potential for quality of life compromise. METHODS: This cross-sectional cohort study evaluated risk factors for admissions and readmissions between October 2014 and March 2016 in adults with SCD (n = 201) and caregivers of children with SCD (n = 330) at six centres across the U.S. Survey items assessed social determinants of health (e.g. educational attainment, difficulty paying bills), depressive symptoms, social support, health literacy, spirituality, missed clinic appointments, and outcomes hospital admissions and 30-day readmissions in the previous year. RESULTS: A majority of adults (64%) and almost half of children (reported by caregivers: 43%) were admitted, and fewer readmitted (adults: 28%; children: 9%). The most common reason for hospitalization was uncontrolled pain (admission: adults: 84%, children: 69%; readmissions: adults: 83%, children: 69%). Children were less likely to have admissions/readmissions than adults (Admissions: OR: 0.35, 95% CI: [0.23,0.52]); Readmissions: 0.23 [0.13,0.41]). For all participants, missing appointments were associated with admissions (1.66 [1.07, 2.58]) and readmissions (2.68 [1.28, 6.29]), as were depressive symptoms (admissions: 1.36 [1.16,1.59]; readmissions: 1.24 [1.04, 1.49]). In adults, difficulty paying bills was associated with more admissions, (3.11 [1.47,6.62]) readmissions (3.7 [1.76,7.79]), and higher spirituality was associated with fewer readmissions (0.39 [0.18,0.81]). DISCUSSION: Missing appointments was significantly associated with admissions and readmissions. Findings confirm that age, mental health, financial insecurity, spirituality, and clinic attendance are all modifiable factors that are associated with admissions and readmissions; addressing them could reduce hospitalizations.


Assuntos
Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Readmissão do Paciente , Adolescente , Adulto , Fatores Etários , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Saúde Mental , Fatores Socioeconômicos , Estados Unidos
16.
Rev Chil Pediatr ; 89(4): 525-529, 2018 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-30571829

RESUMO

Sickle cell disease (SCD) is an autosomal recessive genetic disorder. It is the most frequent structural hemoglobinopathy worldwide, and it is produced by an alteration in the globin chain genes. In Chile, there is no data on the prevalence of SCD since it is considered a very rare condition. The incidence of this disease has been increasing due to migration of people from areas with greater presence of SCD. It is important to know and consider this diagnosis in a selected group of patients with anemia, in order to prevent and treat the different complications of this disease. This article reviews the most recent information that shows new concepts in the knowledge of the physiopathology, and especially publications of guidelines and consensus in relation to the diagnosis and management of this con dition.


Assuntos
Anemia Falciforme , Anemia Falciforme/diagnóstico , Anemia Falciforme/fisiopatologia , Anemia Falciforme/terapia , Terapia Combinada , Diagnóstico Diferencial , Humanos , Prognóstico
17.
Health Qual Life Outcomes ; 16(1): 176, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30200992

RESUMO

PURPOSE: To assess the quality of life (QoL) of caregivers of children with sickle cell disease (SCD) and to determine the risk factors associated with poor QoL. METHOD: A cross sectional study was conducted between 01 and 30 June 2015, in a tertiary care center in western Saudi Arabia to assess various dimensions of QoL by using TNO-AZL Questionnaire for Adult's Health-related Quality of Life (TAAQOL). A total 164 adult caregivers (aged 16 years or more) of children with SCD, who were regularly visiting the department were enrolled (refusal rate = 61.6%). The questionnaire scores were transformed into 0-100 scale; with higher scores indicating less difficulty and better QoL Demographic, socioeconomic data and a satisfaction questionnaire regarding participants' lifestyle were collected and analyzed as risk factors for impaired QoL, by comparing different QoL dimensions' scores using independent t-test, Oneway ANOVA, or linear regression, as appropriate. RESULTS: Sixty-three caregivers were included; 79.4% were mothers, age range 21-71 years, 64.5% were from low social class receiving insufficient support and financial needs were unmet for considerable number of families. Analysis of QoL using TAAQOL showed that emotions (median [75th centile] = 44.44 [66.67] for negative and 61.11 [72.22] for positive emotions), sleep quality (66.67 [91.67]) and sexual life (50.00 [83.33]) were the most affected dimensions. Professional achievement (91.67 [100]), cognitive skills (83.33 [100]), and social contact (100 [100]) were relatively preserved. Negative emotions were more marked in mothers and mostly predicted by satisfaction with social relations notably with partner (B = 3.14, p = 0.016), friends (B = 2.51, p = 0.015) and relatives (B = 2.69, p = 0.016). Positive emotions were predicted by the levels of satisfaction of the caregiver with his/her health (B = 2.56, p = 0.001), job achievement (B = 4.54, p = 0.001), living conditions (B = 2.60, p = 0.034) and the condition of the diseased child (B = 2.55, p = 0.011). A strong correlation was found between sleep quality and cognitive skills. CONCLUSION: There are notable financial and emotional burdens on the caregivers of children with SCD affecting various aspects of their QoL, which are likely to be impacted by the individual levels of social and professional achievement. Physicians and health authorities should give particular attention to the QoL of caregivers and families of children with SCD, to help them cope up with the disease and overcome its related psychological and financial impacts.


Assuntos
Anemia Falciforme/psicologia , Anemia Falciforme/terapia , Cuidadores/psicologia , Pais/psicologia , Qualidade de Vida/psicologia , Adaptação Psicológica , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Arábia Saudita , Perfil de Impacto da Doença , Inquéritos e Questionários , Adulto Jovem
19.
Emerg Med Clin North Am ; 36(3): 567-576, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30037443

RESUMO

Emergency providers are likely to encounter sickle cell disease-related emergencies. The pathophysiology of emergent complaints are usually related to either an acute anemia or a vasoocclusive crisis. Differentiating between the two is the first step in the workup. Anemic crises must then be differentiated by the source. Vasoocclusive crises must be appropriately treated with aggressive pain management, gentle hydration, and other appropriate adjuncts. Early recognition and treatment are key in providing excellent emergency care to those with sickle cell disease.


Assuntos
Anemia Falciforme/complicações , Transfusão de Sangue/métodos , Emergências , Manejo da Dor/métodos , Dor/etiologia , Adulto , Anemia Falciforme/terapia , Humanos , Masculino
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