RESUMO
ABSTRACT: Sickle cell disease (SCD) is an important topic for emergency medicine audiences because complications of the disease account for a large proportion of hematologic emergencies that are seen in the emergency department each year. Early recognition and aggressive management of emergency complications of SCD can help to reduce the morbidity and mortality associated with this disease. Although the treatment recommendations for some complications of SCD are based on expert opinion, there has been advancement in the understanding of the pathogenesis of the disease and evidence regarding the treatment options available for managing acute complications. This continuing medical education article will provide a summary of the clinical manifestation and management of the most common acute complications of SCD: infection, vaso-occlusive episode, acute chest syndrome, splenic sequestration, stroke, and priapism.
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Anemia Falciforme , Serviço Hospitalar de Emergência , Criança , Humanos , Síndrome Torácica Aguda/terapia , Síndrome Torácica Aguda/etiologia , Anemia Falciforme/terapia , Anemia Falciforme/complicações , Priapismo/terapia , Priapismo/etiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/prevenção & controleRESUMO
Sickle cell disease (SCD) is associated with a high occurrence of complications due to vaso-occlusive phenomenon such as stroke. This retrospective cohort study aimed to examine the clinical and laboratory characteristics of 120 children and adolescents with SCD and analyze the factors associated with overt stroke incidence. All relevant data were obtained from patient medical records. Survival analysis was used to compare the demographic, clinical, and laboratory characteristics between patients with and those without overt stroke. The patients were 52.5% female with a mean (SD) age of 11.2 (4.3) years. The incidence of overt stroke in this cohort was nine out of 956.7 patient-years, resulting in an incidence density of 0.94 cases/100 patient-years. Reports of greater than or equal to two previous attacks of dactylitis and greater than or equal to three episodes of acute chest syndrome (ACS)/pneumonia were associated with overt stroke and an increase in reticulocyte count and red blood cell distribution width (RDW). In conclusion, a history of a high number of dactylitis, ACS/pneumonia, increased RDW, and reticulocytosis was associated with overt stroke occurrence in children and adolescents with SCD. Future studies with a higher stroke incidence in the evaluated sample are necessary to confirm this hypothesis.
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Síndrome Torácica Aguda , Anemia Falciforme , Pneumonia , Acidente Vascular Cerebral , Criança , Humanos , Adolescente , Feminino , Masculino , Estudos Retrospectivos , Hidroxiureia , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Síndrome Torácica Aguda/etiologia , Síndrome Torácica Aguda/complicações , Pneumonia/complicaçõesRESUMO
BACKGROUND: Acute chest syndrome (ACS) is a leading cause of death in patients with sickle cell disease. Lung ultrasound (LUS) is emerging as a point-of-care method to diagnose ACS, allowing for more rapid diagnosis in the ED setting and sparing patients from ionizing radiation exposure. RESEARCH QUESTION: What is the diagnostic accuracy of LUS for ACS diagnosis, using the current reference standard of chest radiography? STUDY DESIGN AND METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed for this systematic review and meta-analysis. Embase, MEDLINE, Web of Science, and Google Scholar were used to compile all relevant studies. Two reviewers screened the studies for inclusion in this review. Cases of discrepancy were resolved by a third reviewer. Meta-analyses were conducted using both metadta and midas STATA software packages to retrieve summary receiver operating characteristic curves, sensitivities, and specificities. Three reviewers scored the studies with QUADAS-2 for risk of bias assessment. RESULTS: From a total of 713 unique studies retrieved, six studies were included in the final quantitative synthesis. Of these, five studies were in pediatric EDs. Two studies were conference abstracts and not published manuscripts. Data were available for 625 possible ACS cases (97% of cases in patients aged ≤ 21 years) and 95 confirmed ACS diagnoses (pretest probability of 15.2%). The summary sensitivity was 0.92 (95% CI, 0.68-0.98) and the summary specificity was 0.89 (95% CI, 0.69-0.97) with an area under the curve of the summary receiver operating characteristic curve of 0.96 (95% CI, 0.94-0.97). INTERPRETATION: LUS has excellent sensitivity and very good specificity for ACS diagnosis and may serve as an initial point-of-care test to facilitate rapid treatment of ACS and spare pediatric patients from ionizing radiation; however, further research is warranted to improve the generalizability to the adult sickle cell disease population.
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Síndrome Torácica Aguda , Anemia Falciforme , Adulto , Humanos , Criança , Síndrome Torácica Aguda/diagnóstico por imagem , Síndrome Torácica Aguda/etiologia , Sensibilidade e Especificidade , Pulmão/diagnóstico por imagem , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico por imagem , Testes Diagnósticos de RotinaRESUMO
BACKGROUND: Bronchodilators are used to treat bronchial hyper-responsiveness in asthma. Bronchial hyper-responsiveness may be a component of acute chest syndrome in people with sickle cell disease. Therefore, bronchodilators may be useful in the treatment of acute chest syndrome. This is an update of a previously published Cochrane Review. OBJECTIVES: The aim of the review is to determine whether the use of inhaled, short-acting bronchodilators for acute chest syndrome reduces morbidity and mortality in people with sickle cell disease and to assess whether this treatment causes adverse effects. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional searches were carried out on MEDLINE (1966 to 2004) and Embase (1981 to 2004) and ongoing trial registries (28 September 2022). Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 25 July 2022. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials. Trials using quasi-randomisation methods will be included in future updates of this review if there is sufficient evidence that the treatment and control groups are similar at baseline. DATA COLLECTION AND ANALYSIS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. MAIN RESULTS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: If bronchial hyper-responsiveness is an important component of some episodes of acute chest syndrome in people with sickle cell disease, the use of inhaled bronchodilators may be indicated. There is need for a well-designed, adequately-powered randomised controlled trial to assess the benefits and risks of the addition of inhaled bronchodilators to established therapies for acute chest syndrome in people with sickle cell disease.
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Síndrome Torácica Aguda , Anemia Falciforme , Asma , Humanos , Síndrome Torácica Aguda/tratamento farmacológico , Síndrome Torácica Aguda/etiologia , Broncodilatadores/uso terapêutico , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , BrônquiosRESUMO
BACKGROUND: Acute chest syndrome (ACS) is a leading cause of morbidity and mortality in sickle cell patients, and it is often challenging to establish its diagnosis. PROCEDURE: This was a prospective observational study conducted in a pediatric emergency (PEM) department. We aimed to investigate the performance characteristics of point-of-care lung ultrasound (LUS) for diagnosing ACS in sickle cell children. LUS by trained PEM physicians was performed and interpreted as either positive or negative for consolidation. LUS results were compared to chest X-ray (CXR) and discharge diagnosis as reference standards. RESULTS: Four PEM physicians performed the LUS studies in 79 suspected ACS cases. The median age was 8 years (range 1-17 years). Fourteen cases (18%) received a diagnosis of ACS based on CXR and 21 (26.5%) had ACS discharge diagnosis. Comparing to CXR interpretation as the reference standard, LUS had a sensitivity of 100% (95% CI: 77%-100%), specificity of 68% (95% CI: 56%-79%), positive predictive value of 40% (95% CI: 24%-56%), and negative predictive value of 100% (95% CI: 92%-100%). Overall LUS accuracy was 73.42% (95% CI: 62%-83%). Using discharge diagnosis as the endpoint for both CXR and LUS, LUS had significantly higher sensitivity (100% vs. 62%, p = .0047) and lower specificity (76% vs.100%, p = .0002). LUS also had lower positive (60% vs.100%, p < .0001) and higher negative (100% vs.77%, p = .0025) predictive values. The overall accuracy was similar for both tests (82% vs. 88%, p = .2593). CONCLUSION: The high negative predictive value, with narrow CIs, makes LUS an excellent ruling-out tool for ACS.
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Síndrome Torácica Aguda , Pneumonia , Síndrome Torácica Aguda/diagnóstico por imagem , Síndrome Torácica Aguda/etiologia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Pulmão/diagnóstico por imagem , Pneumonia/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Prospectivos , Radiografia Torácica/métodos , Ultrassonografia/métodos , Raios XRESUMO
Sickle cell anaemia (SCA) is a debilitating genetic haemoglobinopathy predominantly affecting the disenfranchised strata of society in Africa and the Americas. The most common pharmacological treatment for this disease is the administration of hydroxycarbamide (HC) for which questions remain regarding its mechanism of action, efficacy and long-term toxicity specifically in paediatric individuals. A multiplatform metabolomics approach was used to assess the metabolome of plasma samples from a population of children and adolescents with SCA with and without HC treatment along with non-SCA individuals. Fifty-three metabolites were identified by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and 1 H nuclear magnetic resonance (NMR) with a predominance of membrane lipids, amino acids and organic acids. The partial least-squares discriminant analysis (PLS-DA) analysis allowed a clear discrimination between the different studied groups, revealing clear effects of the HC treatment in the patients' metabolome including rescue of specific metabolites to control levels. Increased creatine/creatinine levels under HC treatment suggests a possible increase in the arginine pool and increased NO synthesis, supporting existing models for HC action in SCA. The metabolomics results extend the current knowledge on the models for SCA pathophysiology including impairment of Lands' cycle and increased synthesis of sphingosine 1-phosphate. Putative novel biomarkers are suggested.
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Anemia Falciforme/sangue , Antidrepanocíticos/uso terapêutico , Hidroxiureia/uso terapêutico , Metabolômica , Ácidos/sangue , Síndrome Torácica Aguda/etiologia , Adolescente , Aminoácidos/sangue , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/farmacologia , Arteriopatias Oclusivas/etiologia , Biomarcadores , Butiratos/sangue , Criança , Cromatografia Líquida de Alta Pressão , Creatina/sangue , Creatinina/sangue , Feminino , Humanos , Hidroxiureia/farmacologia , Lisofosfolipídeos/sangue , Masculino , Espectrometria de Massas , Lipídeos de Membrana/sangue , Modelos Biológicos , Ressonância Magnética Nuclear Biomolecular , Esfingosina/análogos & derivados , Esfingosina/sangueRESUMO
BACKGROUND: The greatest disease burden of sickle cell disease occurs early in life. Understanding factors that reduce disease related events in this period is therefore important. Hence, we assessed the impact of early care at a specialist center on the incidence of acute events during the first five years. METHODS: This was a retrospective cohort study among Jamaican children with sickle cell disease. Medical records of patients born January, 2004 to December, 2009, who were registered at the Sickle Cell Unit, a specialist care facility, were abstracted for dates of initiation to care, first occurrence and frequency of the outcomes of interest (vaso-occlusive crises, acute splenic sequestration, acute chest syndrome, and infection). Patients were classified according to whether initiation of care was before (early) or after 5 months of age (late). Using standardized t-tests, χ2 tests, and a multiple-failure survival analysis the rates of acute events between groups were compared. RESULTS: Of the total study group (n= 290), homozygous sickle cell disease accounted for 97% and 95% of the early (n=113) and late groups (n=177) respectively. The mean age of presentation in the early and late group was 0.2 and 2.3 years (p<0.01), with a mean length of follow-up of 5.2 and 3.2 years respectively (p<0.01). Vaso-occlusive crisis (n=880) and acute chest syndrome (n= 571) together accounted for 91.6% of the total number of events (n=1584). The risk of vaso-occlusive crisis and acute chest syndrome (among patients who presented with these acute events) was significantly higher in the "late" group, by 43% (Incidence rate ratio, (IRR) = 1.43, p<0.001); 95% CI (1.18-1.72) and 40% (IRR=1.40. p=0.002), 95% CI (1.12-1.75) respectively compared to "early" group. There was no difference in risk between groups for acute splenic sequestration and infection among persons presenting with these events. CONCLUSION: The risk of acute events in children with sickle cell disease exposed to early care at a specialist care is significantly less. Therefore, widespread screening with rapid referral to a specialist center stands to reduce substantial morbidity in Jamaica and other regions with high prevalence of sickle cell disease.
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Síndrome Torácica Aguda , Anemia Falciforme , Síndrome Torácica Aguda/epidemiologia , Síndrome Torácica Aguda/etiologia , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Criança , Pré-Escolar , Homozigoto , Humanos , Lactente , Estudos Retrospectivos , EspecializaçãoRESUMO
Stroke is a severe clinical manifestation of sickle cell anemia (SCA). Despite the prognostic relevance of transcranial Doppler (TCD), more accurate tools to assess stroke risk in children with SCA are required. Here, we describe the effect of clinical, laboratory, and molecular features on the risk of stroke and high-risk TCD in children from the newborn cohort of Minas Gerais, Brazil. Outcomes studied were acute cerebral ischemia and high-risk TCD. Clinical and hematological data were retrieved from children's records. Genetic markers, which were known for their association with stroke risk, were genotyped by polymerase chain reaction/restriction fragment length polymorphism and sequencing. The cumulative incidence of acute cerebral ischemia by the age of 8 years was 7.4 % and that of high-risk TCD by the age of 11.5 years was 14.2 %. The final multivariate model for acute cerebral ischemia risk included high white blood cell count and reticulocyte count, acute chest syndrome rate, and the single nucleotide polymorphisms (SNPs) TEK rs489347 and TNF-α rs1800629. The model for high-risk TCD included high reticulocyte count and the SNPs TEK rs489347 and TGFBR3 rs284875. Children with risk factors should be considered for intensive risk monitoring and for intervention therapy.
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Anemia Falciforme/complicações , Isquemia Encefálica/sangue , Contagem de Reticulócitos , Síndrome Torácica Aguda/etiologia , Doença Aguda , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Criança , Feminino , Seguimentos , Haplótipos , Humanos , Incidência , Recém-Nascido , Contagem de Leucócitos , Masculino , Polimorfismo de Nucleotídeo Único , Proteoglicanas/genética , Receptor TIE-2/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Risco , Fatores de Risco , Fator de Necrose Tumoral alfa/genética , Ultrassonografia Doppler Transcraniana , Globinas beta/genéticaRESUMO
Phenotypic heterogeneity for sickle cell disease is associated to several genetic factors such as genotype for sickle cell disease, ß-globin gene cluster haplotypes and Hb F levels. The coinheritance of Hb S (HBB: c.20A > T) and Hb D-Punjab (HBB: c.364G > C) results in a double heterozygosity, which constitutes one of the genotypic causes of sickle cell disease. This study aimed to assess the phenotypic diversity of sickle cell disease presented by carriers of the Hb S/Hb D-Punjab genotype and the Bantu [- + - - - -] haplotype. We evaluated medical records from 12 patients with sickle cell disease whose Hb S/Hb D-Punjab genotype and Bantu haplotype were confirmed by molecular analysis. Hb S and Hb D-Punjab levels were quantified by chromatographic analysis. Mean concentrations of Hb S and Hb D-Punjab were 44.8 ± 2.3% and 43.3 ± 1.8%, respectively. Painful crises were present in eight (66.7%) patients evaluated, representing the most common clinical event. Acute chest syndrome (ACS) was the second most prevalent manifestation, occurring in two individuals (16.7%). Three patients were asymptomatic, while another two exhibited greater diversity of severe clinical manifestations. Medical records here analyzed reported a significant clinical diversity in sickle cell disease ranging from the absence of symptoms to wide phenotypic variety. The sickle cell disease genotype, Bantu haplotype and hemoglobin (Hb) levels did not influence the clinical diversity. Thus, we concluded that the phenotypic variation in sickle cell disease was present within a specific genotype for disease regardless of the ß-globin gene cluster haplotypes.
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Anemia Falciforme/genética , Hemoglobina Falciforme/análise , Hemoglobinas Anormais/análise , Fenótipo , Síndrome Torácica Aguda/etiologia , Anemia Falciforme/complicações , Anemia Sideroblástica , Genótipo , Haplótipos , Heterozigoto , Humanos , Dor/etiologia , Globinas beta/genéticaRESUMO
In spite of significant strides in the treatment of sickle cell disease (SCD), SCD crises are still responsible for high morbidity and early mortality. While most patients initially seek care in the acute setting for a seemingly uncomplicated pain episode (pain crisis or vaso-occlusive crisis), this initial event is the primary risk factor for potentially life-threatening complications. The pathophysiological basis of these illnesses is end-organ ischemia and infarction combined with the downstream effects of hemolysis that results from red blood cell sickling. These pathological changes can occur acutely and lead to a dramatic clinical presentation, but are frequently superimposed over a milieu of chronic vasculopathy, immune dysregulation, and decreased functional reserve. In the lungs, acute chest syndrome is a particularly ominous lung injury syndrome with a complex pathogenesis and potentially devastating sequelae, but all organ systems can be affected. It is, therefore, critical to understand the SCD patients' susceptibility to acute complications and their risk factors so that they can be recognized promptly and managed effectively. Blood transfusions remain the mainstay of therapy for all severe acute crises. Recommendations and indications for the safest and most efficient implementation of transfusion strategies in the critical care setting are therefore presented and discussed, together with their pitfalls and potential future therapeutic alternatives. In particular, the importance of extended phenotypic red blood cell matching cannot be overemphasized, due to the high prevalence of severe complications from red cell alloimmunization in SCD.