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1.
Cochrane Database Syst Rev ; 9: CD004448, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32977351

RESUMO

BACKGROUND: Sickle cell disease, a common recessively inherited haemoglobin disorder, affects people from sub-Saharan Africa, the Middle East, Mediterranean basin, Indian subcontinent, Caribbean and South America. It is associated with complications and a reduced life expectancy. Phytomedicines (medicine derived from plants in their original state) encompass many of the plant remedies from traditional healers which the populations most affected would encounter. Laboratory research and limited clinical trials have suggested positive effects of phytomedicines both in vivo and in vitro. However, there has been little systematic appraisal of their benefits. This is an updated version of a previously published Cochrane Review. OBJECTIVES: To assess the benefits and risks of phytomedicines in people with sickle cell disease of all types, of any age, in any setting. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, the International Standard Randomised Controlled Trial Number Register (ISRCTN), the Allied and Complimentary Medicine Database (AMED), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). Dates of most recent searches: Cochrane Cystic Fibrosis and Genetic Disorders Haemoglobinopathies Trials Register: 17 March 2020; ISRCTN: 19 April 2020; AMED: 18 May 2020; ClinicalTrials.gov: 24 April 2020; and the WHO ICTRP: 27 July 2017. SELECTION CRITERIA: Randomised or quasi-randomised trials with participants of all ages with sickle cell disease, in all settings, comparing the administration of phytomedicines, by any mode to placebo or conventional treatment, including blood transfusion and hydroxyurea. DATA COLLECTION AND ANALYSIS: Both authors independently assessed trial quality and extracted data. MAIN RESULTS: Three trials (212 participants) of three phytomedicines: Niprisan® (also known as Nicosan®), Ciklavit® and a powdered extract of Pfaffia paniculata were included. The Phase IIB (pivotal) trial suggests that Niprisan® may be effective in reducing episodes of severe painful sickle cell disease crisis over a six-month period (low-quality evidence). It did not appear to affect the risk of severe complications or the level of anaemia (low-quality evidence). The single trial of Cajanus cajan (Ciklavit®) reported a possible benefit to individuals with painful crises, and a possible adverse effect (non-significant) on the level of anaemia (low-quality evidence). We are uncertain of the effect of Pfaffia paniculata on the laboratory parameters and symptoms of SCD (very low-quality of evidence). No adverse effects were reported with Niprisan® and Pfaffia paniculata (low- to very low-quality evidence). AUTHORS' CONCLUSIONS: While Niprisan® appeared to be safe and effective in reducing severe painful crises over a six-month follow-up period, further trials are required to assess its role in managing people with SCD and the results of its multicentre trials are awaited. Currently, no conclusions can be made regarding the efficacy of Ciklavit® and the powdered root extract of Pfaffia paniculata in managing SCD. Based on the published results for Niprisan® and in view of the limitations in data collection and analysis of the three trials, phytomedicines may have a potential beneficial effect in reducing painful crises in SCD. This needs to be further validated in future trials. More trials with improved study design and data collection are required on the safety and efficacy of phytomedicines used in managing SCD.


Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Adolescente , Adulto , Amaranthaceae/química , Anemia/induzido quimicamente , Anemia Falciforme/sangue , Antidrepanocíticos/efeitos adversos , Criança , Pré-Escolar , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Lactente , Masculino , Fitoterapia/efeitos adversos , Extratos Vegetais/efeitos adversos , Raízes de Plantas/química , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Ann Hematol ; 99(10): 2279-2288, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32772141

RESUMO

Sickle cell disease (SCD) is a monogenic disease characterized by multisystem morbidity and highly variable clinical course. Inter-individual variability in hemoglobin F (HbF) levels is one of the main modifiers that account for the clinical heterogeneity in SCD. HbF levels are affected by, among other factors, single nucleotide polymorphisms (SNPs) at the BCL11A gene and the HBS1L-MYB intergenic region and Xmn1 gene. Our aim was to investigate HbF-enhancer haplotypes at these loci to obtain a first overview of the genetic situation of SCD patients in Egypt and its impact on the severity of the disease. The study included 100 SCD patients and 100 matched controls. Genotyping of BCL11A (rs1886868 C/T), HBS1L-MYB (rs9389268 A/G) and Xmn1 γG158 (rs7842144 C/T) SNPs showed no statistically significant difference between SCD patients and controls except for the hetero-mutant genotypes of BCL11A which was significantly higher in SCD patients compared with controls. Baseline HbF levels were significantly higher in those with co-inheritance of polymorphic genotypes of BCL11A + HSB1L-MYB and BCL11A + Xmn1. Steady-state HbF levels, used as an indicator of disease severity, were significantly higher in SCD-Sß patients having the polymorphic genotypes of HSB1L-MYB. Fold change of HbF in both patient groups did not differ between those harboring the wild and the polymorphic genotypes of the studied SNPs. In conclusion, BCL11A, HSB1L, and Xmn1 genetic polymorphisms had no positive impact on baseline HbF levels solely but had if coexisted. Discovery of the molecular mechanisms controlling HbF production could provide a more effective strategy for HbF induction.


Assuntos
Anemia Falciforme/genética , DNA Intergênico/genética , Hemoglobina Fetal/análise , Proteínas de Ligação ao GTP/genética , Genes myb , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Proteínas Repressoras/genética , gama-Globinas/genética , Adolescente , Alelos , Anemia Falciforme/sangue , Anemia Falciforme/etnologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Desoxirribonucleases de Sítio Específico do Tipo II , Egito , Feminino , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo de Fragmento de Restrição , Adulto Jovem
3.
PLoS One ; 15(8): e0237543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32776978

RESUMO

Sickle cell disease (SCD) impacts liver and kidney function as well as skin integrity. These complications, as well as the hyperinflammatory state of SCD, could affect serum albumin. Serum albumin has key roles in antioxidant, anti-inflammatory and antithrombotic pathways and maintains vascular integrity. In SCD, these pathways modulate disease severity and clinical outcomes. We used three independent SCD adult cohorts to assess clinical predictors of serum albumin as well its association with mortality. In 2553 SCD adult participants, the frequency of low (<35 g/L) serum albumin was 5%. Older age and lower hemoglobin (P <0.001) were associated with lower serum albumin in all three cohorts. In age and hemoglobin adjusted analysis, higher liver enzymes (P <0.05) were associated with lower serum albumin. In two of the three cohorts, lower kidney function as measured by Glomerular Filtration Rate (P<0.001) was associated with lower serum albumin. Lower serum albumin predicted higher risk of tricuspid regurgitation velocity ≥ 2.5 m/s (OR = 1.1 per g/L, P ≤0.01). In all three cohorts, patients with low serum albumin had higher mortality (adjusted HR ≥2.9, P ≤0.003). This study confirms the role of serum albumin as a biomarker of disease severity and prognosis in patients with SCD. Albumin as a biomarker and possible mediator of SCD severity should be studied further.


Assuntos
Anemia Falciforme/mortalidade , Biomarcadores/sangue , Hemoglobinas/análise , Albumina Sérica/análise , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Prognóstico , Taxa de Sobrevida
4.
Niger Postgrad Med J ; 27(3): 190-195, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687118

RESUMO

Background: Haemoglobin (Hb) disorders are among the most common blood genetic disorders worldwide, and they constitute an important cause of morbidity and mortality, especially in Nigeria. Despite the clinical significance of early diagnosis, newborn screening for these conditions is not routinely done in Nigeria. Objective: This study was undertaken to document the pattern of Hb phenotypes of newborn babies at the National Hospital Abuja and highlight the relevance of neonatal screening for early diagnosis of abnormal Hb phenotypes in Nigeria. Subjects and Methods: A prospective study of eligible newborn babies delivered in the hospital at the study site was undertaken following parental informed consent. Venous blood was collected from the babies into an ethylenediaminetetraacetic acid sample bottles. The samples were analysed using high-performance liquid chromatography (HPLC) techniques, and the Hb phenotypes obtained were documented. Data were analysed using the Statistical Package for Social Sciences (SPSS) version 20 (IBM-SPSS, Armonk, NY, USA). Results: Three hundred and eleven newborns (male = 173, female = 138) aged 0-28 days were recruited. Two hundred and thirty-six (75.9%) babies had Hb AA (FA) phenotype, 63 (20.3%) Hb AS (FAS), 6 (1.9%) Hb SS (FS), 4 (1.3%) Hb AC (FAC) and 2 (0.6%) had abnormal HbA variants. The overall prevalence of abnormal Hb phenotype was 24.1%. The results showed a significant association of sex (P = 0.003) and ethnicity (P = 0.047) with Hb phenotype. Conclusion: There is a wide spectrum of abnormal Hb phenotypes in Nigeria, and these phenotypes can easily be detected at birth using HPLC. We, therefore, recommend routine neonatal screening for sickle cell disease by HPLC in Nigeria.


Assuntos
Anemia Falciforme/sangue , Cromatografia Líquida de Alta Pressão/métodos , Hemoglobinas Anormais/análise , Hemoglobinas/análise , Recém-Nascido/sangue , Traço Falciforme/sangue , Adolescente , Adulto , Grupo com Ancestrais do Continente Africano , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Criança , Pré-Escolar , Hemoglobina Falciforme , Hemoglobinas/classificação , Hemoglobinas Anormais/genética , Humanos , Lactente , Nigéria/epidemiologia , Fenótipo , Prevalência , Estudos Prospectivos , Adulto Jovem
5.
Ann Hematol ; 99(9): 2047-2055, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32691114

RESUMO

Manual erythroexchange (MEEX) was proven to be effective and safe in the management of sickle cell disease (SCD). The goal is to quickly reduce the percentage of hemoglobin S (HbS%). A national survey of the Italian Society for Thalassemia and Hemoglobinopathies (SITE) observed a great variability among MEEX protocols none of which were found to be predictive of the values of HbS% and hemoglobin (Hb) after the exchange. Two equations to estimate the HbS% and Hb values to be obtained after MEEX were developed based on the results of the MEEX procedures in place in the centers participating in the present study. A standard protocol was subsequently defined to evaluate the volumes to exchange to obtain the target values of HbS% and Hb. The protocol was tested in 261 MEEX performed in SCD patients followed in the 5 participating centers that belong to the Italian Hemoglobinopathy Comprehensive Care Network, with the support of the SITE. The results showed a correlation between the estimated and measured values of HbS% and Hb (Rp 0.95 and 0.65 respectively, p < 0.001). A negligible bias was found for the prediction of HbS% and a bias of 1 g/dl for Hb. From consecutive MEEX, a rate of increase of HbS% between two exchanges of around 0.4% per day (p < 0.001) was measured. This protocol was shown to be effective and safe, as all patients reached the target value of HbS%. All the MEEX procedures were carried out with single venous access. No adverse events or reactions such as hypotension or electrolyte imbalance were reported nor were any complaints concerning the procedures received from patients.


Assuntos
Anemia Falciforme/sangue , Anemia Falciforme/terapia , Determinação do Volume Sanguíneo/normas , Volume Sanguíneo/fisiologia , Transfusão de Eritrócitos/normas , Hemoglobina Falciforme/metabolismo , Adulto , Anemia Falciforme/epidemiologia , Determinação do Volume Sanguíneo/métodos , Transfusão de Eritrócitos/métodos , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto Jovem
6.
Clin Appl Thromb Hemost ; 26: 1076029620943671, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702995

RESUMO

Severe acute respiratory syndrome coronavirus 2 infection (COVID-19) is known to induce severe inflammation and activation of the coagulation system, resulting in a prothrombotic state. Although inflammatory conditions and organ-specific diseases have been shown to be strong determinants of morbidity and mortality in patients with COVID-19, it is unclear whether preexisting differences in coagulation impact the severity of COVID-19. African Americans have higher rates of COVID-19 infection and disease-related morbidity and mortality. Moreover, African Americans are known to be at a higher risk for thrombotic events due to both biological and socioeconomic factors. In this review, we explore whether differences in baseline coagulation status and medical management of coagulation play an important role in COVID-19 disease severity and contribute to racial disparity trends within COVID-19.


Assuntos
Afro-Americanos , Betacoronavirus , Infecções por Coronavirus/etnologia , Pandemias , Pneumonia Viral/etnologia , Trombofilia/etnologia , Tromboembolia Venosa/etnologia , Afro-Americanos/genética , Anemia Falciforme/sangue , Anemia Falciforme/etnologia , Anticoagulantes/uso terapêutico , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/genética , Ensaios Clínicos como Assunto , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Fator VIII/análise , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Estudos de Associação Genética , Predisposição Genética para Doença , Disparidades em Assistência à Saúde , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Seleção de Pacientes , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Polimorfismo de Nucleotídeo Único , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etnologia , Fatores de Risco , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Trombofilia/sangue , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
7.
Cochrane Database Syst Rev ; 7: CD003149, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32614473

RESUMO

BACKGROUND: Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Surgical interventions are more common in people with SCD, and occur at much younger ages than in the general population. Blood transfusions are frequently used prior to surgery and several regimens are used but there is no consensus over the best method or the necessity of transfusion in specific surgical cases. This is an update of a Cochrane Review. OBJECTIVES: To determine whether there is evidence that preoperative blood transfusion in people with SCD undergoing elective or emergency surgery reduces mortality and perioperative or sickle cell-related serious adverse events. To compare the effectiveness of different transfusion regimens (aggressive or conservative) if preoperative transfusions are indicated in people with SCD. SEARCH METHODS: We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 28 January 2020 We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 19 September 2019. SELECTION CRITERIA: All randomised controlled trials and quasi-randomised controlled trials comparing preoperative blood transfusion regimens to different regimens or no transfusion in people with SCD undergoing elective or emergency surgery. There was no restriction by outcomes examined, language or publication status. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and the risk of bias and extracted data. MAIN RESULTS: Three trials with 990 participants were eligible for inclusion in the review. There were no ongoing trials identified. These trials were conducted between 1988 and 2011. The majority of people included had haemoglobin (Hb) SS SCD. The majority of surgical procedures were considered low or intermediate risk for developing sickle cell-related complications. Aggressive versus simple red blood cell transfusions One trial (551 participants) compared an aggressive transfusion regimen (decreasing sickle haemoglobin to less than 30%) to a simple transfusion regimen (increasing haemoglobin to 100 g/L). This trial re-randomised participants and therefore quantitative analysis was only possible on two subsets of data: participants undergoing cholecystectomy (230 participants); and participants undergoing tonsillectomy or adenoidectomy surgeries (107 participants). Data were not combined as we do not know if any participant received both surgeries. Overall, the quality of the evidence was very low across different outcomes according to GRADE methodology. This was due to the trial being at high risk of bias primarily due to lack of blinding, indirectness and the outcome estimates being imprecise. Cholecystectomy subgroup results are reported in the abstract. Results for both subgroups were similar. There was no difference in all-cause mortality between people receiving aggressive transfusions and those receiving conservative transfusions. No deaths occurred in either subgroup. There were no differences between the aggressive transfusion group and conservative transfusion group in the number of people developing: • an acute chest syndrome, risk ratio (RR) 0.84 (95% confidence interval (CI) 0.38 to 1.84) (one trial, 230 participants, very low-quality evidence); • vaso-occlusive crisis, risk ratio 0.30 (95% CI 0.09 to 1.04) (one trial, 230 participants, very low quality evidence); • serious infection, risk ratio 1.75 (95% CI 0.59 to 5.18) (one trial, 230 participants, very low-quality evidence); • any perioperative complications, RR 0.75 (95% CI 0.36 to 1.55) (one trial, 230 participants, very low-quality evidence); • a transfusion-related complication, RR 1.85 (95% CI 0.89 to 3.88) (one trial, 230 participants, very low-quality evidence). Preoperative transfusion versus no preoperative transfusion Two trials (434 participants) compared a preoperative transfusion plus standard care to a group receiving standard care. Overall, the quality of the evidence was low to very low across different outcomes according to GRADE methodology. This was due to the trials being at high risk of bias due to lack of blinding, and outcome estimates being imprecise. One trial was stopped early because more people in the no transfusion arm developed an acute chest syndrome. There was no difference in all-cause mortality between people receiving preoperative transfusions and those receiving no preoperative transfusions (two trials, 434 participants, no deaths occurred). There was significant heterogeneity between the two trials in the number of people developing an acute chest syndrome, a meta-analysis was therefore not performed. One trial showed a reduced number of people developing acute chest syndrome between people receiving preoperative transfusions and those receiving no preoperative transfusions, risk ratio 0.11 (95% confidence interval 0.01 to 0.80) (65 participants), whereas the other trial did not, RR 4.81 (95% CI 0.23 to 99.61) (369 participants). There were no differences between the preoperative transfusion groups and the groups without preoperative transfusion in the number of people developing: • a vaso-occlusive crisis, Peto odds ratio (OR) 1.91 (95% confidence interval 0.61 to 6.04) (two trials, 434 participants, very low-quality evidence). • a serious infection, Peto OR 1.29 (95% CI 0.29 to 5.71) (two trials, 434 participants, very low-quality evidence); • any perioperative complications, RR 0.24 (95% CI 0.03 to 2.05) (one trial, 65 participants, low-quality evidence). There was an increase in the number of people developing circulatory overload in those receiving preoperative transfusions compared to those not receiving preoperative transfusions in one of the two trials, and no events were seen in the other trial (no meta-analysis performed). AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised trials to determine whether conservative preoperative blood transfusion is as effective as aggressive preoperative blood transfusion in preventing sickle-related or surgery-related complications in people with HbSS disease. There is very low quality evidence that preoperative blood transfusion may prevent development of acute chest syndrome. Due to lack of evidence this review cannot comment on management for people with HbSC or HbSß+ disease or for those with high baseline haemoglobin concentrations.


Assuntos
Anemia Falciforme/cirurgia , Transfusão de Sangue/métodos , Hemoglobina Falciforme , Cuidados Pré-Operatórios/métodos , Síndrome Torácica Aguda/etiologia , Adenoidectomia , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Colecistectomia/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tonsilectomia , Reação Transfusional
8.
Cochrane Database Syst Rev ; 7: CD003146, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32716555

RESUMO

BACKGROUND: Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Stroke affects around 10% of children with sickle cell anaemia (HbSS). Chronic blood transfusions may reduce the risk of vaso-occlusion and stroke by diluting the proportion of sickled cells in the circulation. This is an update of a Cochrane Review first published in 2002, and last updated in 2017. OBJECTIVES: To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease for primary and secondary stroke prevention (excluding silent cerebral infarcts). SEARCH METHODS: We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 8 October 2019. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 19 September 2019. SELECTION CRITERIA: Randomised controlled trials comparing red blood cell transfusions as prophylaxis for stroke in people with sickle cell disease to alternative or standard treatment. There were no restrictions by outcomes examined, language or publication status. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and the risk of bias and extracted data. MAIN RESULTS: We included five trials (660 participants) published between 1998 and 2016. Four of these trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of sickle cell disease. Three trials compared regular red cell transfusions to standard care in primary prevention of stroke: two in children with no previous long-term transfusions; and one in children and adolescents on long-term transfusion. Two trials compared the drug hydroxyurea (hydroxycarbamide) and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children); and one in secondary prevention (children and adolescents). The quality of the evidence was very low to moderate across different outcomes according to GRADE methodology. This was due to the trials being at a high risk of bias due to lack of blinding, indirectness and imprecise outcome estimates. Red cell transfusions versus standard care Children with no previous long-term transfusions Long-term transfusions probably reduce the incidence of clinical stroke in children with a higher risk of stroke (abnormal transcranial doppler velocities or previous history of silent cerebral infarct), risk ratio 0.12 (95% confidence interval 0.03 to 0.49) (two trials, 326 participants), moderate quality evidence. Long-term transfusions may: reduce the incidence of other sickle cell disease-related complications (acute chest syndrome, risk ratio 0.24 (95% confidence interval 0.12 to 0.48)) (two trials, 326 participants); increase quality of life (difference estimate -0.54, 95% confidence interval -0.92 to -0.17) (one trial, 166 participants); but make little or no difference to IQ scores (least square mean: 1.7, standard error 95% confidence interval -1.1 to 4.4) (one trial, 166 participants), low quality evidence. We are very uncertain whether long-term transfusions: reduce the risk of transient ischaemic attacks, Peto odds ratio 0.13 (95% confidence interval 0.01 to 2.11) (two trials, 323 participants); have any effect on all-cause mortality, no deaths reported (two trials, 326 participants); or increase the risk of alloimmunisation, risk ratio 3.16 (95% confidence interval 0.18 to 57.17) (one trial, 121 participants), very low quality evidence. Children and adolescents with previous long-term transfusions (one trial, 79 participants) We are very uncertain whether continuing long-term transfusions reduces the incidence of: stroke, risk ratio 0.22 (95% confidence interval 0.01 to 4.35); or all-cause mortality, Peto odds ratio 8.00 (95% confidence interval 0.16 to 404.12), very low quality evidence. Several review outcomes were only reported in one trial arm (sickle cell disease-related complications, alloimmunisation, transient ischaemic attacks). The trial did not report neurological impairment, or quality of life. Hydroxyurea and phlebotomy versus red cell transfusions and chelation Neither trial reported on neurological impairment, alloimmunisation, or quality of life. Primary prevention, children (one trial, 121 participants) Switching to hydroxyurea and phlebotomy may have little or no effect on liver iron concentrations, mean difference -1.80 mg Fe/g dry-weight liver (95% confidence interval -5.16 to 1.56), low quality evidence. We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: risk of stroke (no strokes); all-cause mortality (no deaths); transient ischaemic attacks, risk ratio 1.02 (95% confidence interval 0.21 to 4.84); or other sickle cell disease-related complications (acute chest syndrome, risk ratio 2.03 (95% confidence interval 0.39 to 10.69)), very low quality evidence. Secondary prevention, children and adolescents (one trial, 133 participants) Switching to hydroxyurea and phlebotomy may: increase the risk of sickle cell disease-related serious adverse events, risk ratio 3.10 (95% confidence interval 1.42 to 6.75); but have little or no effect on median liver iron concentrations (hydroxyurea, 17.3 mg Fe/g dry-weight liver (interquartile range 10.0 to 30.6)); transfusion 17.3 mg Fe/g dry-weight liver (interquartile range 8.8 to 30.7), low quality evidence. We are very uncertain whether switching to hydroxyurea and phlebotomy: increases the risk of stroke, risk ratio 14.78 (95% confidence interval 0.86 to 253.66); or has any effect on all-cause mortality, Peto odds ratio 0.98 (95% confidence interval 0.06 to 15.92); or transient ischaemic attacks, risk ratio 0.66 (95% confidence interval 0.25 to 1.74), very low quality evidence. AUTHORS' CONCLUSIONS: There is no evidence for managing adults, or children who do not have HbSS sickle cell disease. In children who are at higher risk of stroke and have not had previous long-term transfusions, there is moderate quality evidence that long-term red cell transfusions reduce the risk of stroke, and low quality evidence they also reduce the risk of other sickle cell disease-related complications. In primary and secondary prevention of stroke there is low quality evidence that switching to hydroxyurea with phlebotomy has little or no effect on the liver iron concentration. In secondary prevention of stroke there is low-quality evidence that switching to hydroxyurea with phlebotomy increases the risk of sickle cell disease-related events. All other evidence in this review is of very low quality.


Assuntos
Anemia Falciforme/complicações , Transfusão de Eritrócitos , Prevenção Primária , Prevenção Secundária , Acidente Vascular Cerebral/prevenção & controle , Adolescente , Anemia Falciforme/sangue , Antidrepanocíticos/efeitos adversos , Antidrepanocíticos/uso terapêutico , Transfusão de Sangue , Criança , Pré-Escolar , Término Precoce de Ensaios Clínicos , Transfusão de Eritrócitos/efeitos adversos , Hemoglobina Falciforme , Humanos , Hidroxiureia/efeitos adversos , Hidroxiureia/uso terapêutico , Quelantes de Ferro/uso terapêutico , Flebotomia/efeitos adversos , Acidente Vascular Cerebral/etiologia , Adulto Jovem
9.
Ann Hematol ; 99(9): 2065-2072, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32572524

RESUMO

Sickle hepatopathy is a severe and not rare complication of sickle cell disease (SCD), showing mainly a cholestatic pattern. So far, no effective approaches to prevent or treat this condition have been recognized. We conducted a single-center observational study in 68 adult sickle cell patients, encompassing 17 with sickle cell anemia (SCA), 38 with sickle cell thalassemia (HbS/ß-Thal), and 13 with HbSC disease. The aim of our study was to assess liver damage in the three main forms of SCD, through the evaluation of clinical, laboratory, and imaging findings. In our population, the role of hepatotropic viruses, high BMI, and alcohol consumption in liver damage was ruled out. SCA and HbS/ß-Thal patients with lower Hb (p < 0.001), higher HbS (p < 0.001), and frequent vaso-occlusive crises showed functional (GGT values: SCA and HbS/ß-Thal vs HbSC p = 0.047 and p = 0.009, respectively) and structural liver abnormalities, defined by abdominal ultrasound and vibration-controlled transient elastography (liver stiffness values: SCA and HbS/ß-Thal vs HbSC p 0.022 and p 0.19, respectively), more severe than HbSC patients. Through univariate and multivariate analyses, male sex, SCA genotype, lower HbF, frequent transfusions, increased GGT values, and abnormal liver ultrasound and stiffness were identified as potentially early markers of sickle hepatopathy.


Assuntos
Anemia Falciforme/sangue , Anemia Falciforme/diagnóstico por imagem , Genótipo , Hepatopatias/sangue , Hepatopatias/diagnóstico por imagem , Adulto , Anemia Falciforme/genética , Feminino , Humanos , Hepatopatias/genética , Masculino , Pessoa de Meia-Idade , Fatores de Risco
10.
Ann Hematol ; 99(7): 1453-1463, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32447424

RESUMO

Fetal hemoglobin (HbF) ameliorates clinical severity of sickle cell anemia (SCA). The major loci regulating HbF levels are HBB cluster, BCL11A, and HMIP-2 (HBS1L-MYB). However, the impact of noncoding single-nucleotide polymorphisms (SNPs) in these loci on clinical outcomes and their functional role on regulating HbF levels should be better elucidated. Therefore, we performed comprehensive association analyses of 14 noncoding SNPs in five loci with HbF levels and with clinical outcomes in a cohort of 250 children with SCA from Southeastern Brazil, and further performed functional annotation of these SNPs. We found SNPs independently associated with HbF levels: rs4671393 in BCL11A (ß-coefficient = 0.28), rs9399137 in HMIP-2A (ß-coefficient = 0.16), and rs4895441 in HMIP-2B (ß-coefficient = 0.15). Patients carrying minor (HbF-boosting) alleles for rs1427407, rs93979137, rs4895441, rs9402686, and rs9494145 showed reduced count of reticulocytes (p < 0.01), while those carrying the T allele of rs9494145 showed lower white blood cell count (p = 0.002). Carriers of the minor allele for rs9402686 showed higher peripheral saturation of oxygen (p = 0.002). Patients carrying minor alleles in BCL11A showed lower risk of transfusion incidence rate ratio (IRR ≥ 1.3; p < 0.0001). This effect was independent of HbF effect (p = 0.005). Carriers of minor alleles for rs9399137 and rs9402686 showed lower risk of acute chest syndrome (IRR > 1.3; p ≤ 0.01). Carriers of the reference allele for rs4671393 showed lower risk of infections (IRR = 1.16; p = 0.01). In conclusion, patients carrying HbF-boosting alleles of BCL11A and HMIP-2 were associated with milder clinical phenotypes. Higher HbF concentration may underlie this effect.


Assuntos
Anemia Falciforme/diagnóstico , Anemia Falciforme/genética , Hemoglobina Fetal/metabolismo , Proteínas de Ligação ao GTP/genética , Genes myb , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Alelos , Anemia Falciforme/sangue , Anemia Falciforme/epidemiologia , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hemoglobina Fetal/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos
11.
Pediatr Blood Cancer ; 67(8): e28250, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32386106

RESUMO

BACKGROUND: Hydroxyurea nonadherence is common among children with sickle cell disease (SCD), but it is unclear if current adherence measures are valid compared with video directly observed therapy (VDOT), a reference method. The objectives were to evaluate if hydroxyurea adherence by pharmacy records, urine assay, mean corpuscular volume (MCV), and/or fetal hemoglobin (HbF) correlated with and was sensitive and specific compared with VDOT. METHODS: This was a cross-sectional analysis of adherence data from 34 children with SCD on a single-arm, six-month hydroxyurea adherence study. Spearman correlation coefficient compared participants' adherence by pharmacy records, MCV, and HbF to adherence by VDOT. The sensitivity and specificity of ≥80% adherence by pharmacy records, two urine samples with hydroxyurea, MCV ≥100 fl/L, and HbF ≥20% compared with ≥80% VDOT adherence were also calculated. RESULTS: Median pharmacy and VDOT adherence rates were similar (87.8% vs 88.1%, P = 0.75) and mildly correlated (rs  = 0.45; P = 0.008) but the sensitivity of ≥80% adherence by pharmacy records was 72.7% and specificity was 45.5%. MCV (rs  = -0.02, P = 0.92) and HbF (rs  = -0.2, P = 0.33) did not significantly correlate with VDOT adherence. Sensitivity and specificity were 83.3% and 33.3% for having two urine samples with hydroxyurea, 35% and 71.4% for MCV ≥100 fl/L, and 75% and 0% for HbF ≥20%, respectively. CONCLUSIONS: Commonly used tools to measure hydroxyurea adherence may not correlate with or be valid compared with video adherence. Future studies to refine these measures are needed to effectively target adherence interventions to children with SCD who have the potential to benefit. (ClinicalTrials.gov NCT02578017).


Assuntos
Anemia Falciforme , Hidroxiureia/administração & dosagem , Adesão à Medicação , Gravação em Vídeo , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Criança , Pré-Escolar , Estudos Transversais , Índices de Eritrócitos , Feminino , Hemoglobina Fetal/metabolismo , Humanos , Masculino , Registros Médicos
12.
Ann Hematol ; 99(9): 2073-2079, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32377816

RESUMO

Vasculopathy is a hallmark of sickle cell disease ultimately resulting in chronic end organ damage. Leg ulcer is one of its sequelae, occurring in ~ 5-10% of adult sickle cell patients. The majority of leg ulcer publications to date have emanated from single center cohort studies. As such, there are limited studies on the geographic distribution of leg ulcers and associated risk factors worldwide. The Consortium for the Advancement of Sickle Cell Research (CASiRe) was formed to improve the understanding of the different phenotypes of sickle cell disease patients living in different geographic locations around the world (USA, UK, Italy, Ghana). This cross-sectional cohort sub-study of 659 sickle cell patients aimed to determine the geographic distribution and risk factors associated with leg ulcers. The prevalence of leg ulcers was 10.3% and was associated with older age, SS genotype, male gender, and Ghanaian origin. In fact, the highest prevalence (18.6%) was observed in Ghana. Albuminuria, proteinuria, increased markers of hemolysis (lower hemoglobin, higher total bilirubin), lower oxygen saturation, and lower body mass index were also associated with leg ulceration. Overall, our study identified a predominance of leg ulcers within male hemoglobin SS patients living in sub-Saharan Africa with renal dysfunction and increased hemolysis.


Assuntos
Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Internacionalidade , Úlcera da Perna/diagnóstico , Úlcera da Perna/epidemiologia , Adolescente , Adulto , Idoso , Anemia Falciforme/sangue , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Gana/epidemiologia , Humanos , Lactente , Itália/epidemiologia , Úlcera da Perna/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Reino Unido/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
13.
Cochrane Database Syst Rev ; 5: CD010858, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32462740

RESUMO

BACKGROUND: Sickle cell disease (SCD) is a genetic chronic haemolytic and pro-inflammatory disorder. With increased catabolism and deficits in energy and nutrient intake, individuals with SCD suffer multiple macro- and micro-nutritional deficiencies, including vitamin D deficiency. This is an update of a previous review. OBJECTIVES: To investigate the effects of vitamin D supplementation in children and adults with SCD and to compare different dose regimens. To determine the effects of vitamin D supplementation on general health (e.g. growth status and health-related quality of life), on musculoskeletal health (including bone mineral density, pain crises, bone fracture and muscle health), on respiratory health (including lung function, acute chest syndrome, acute exacerbation of asthma and respiratory infections) and the safety of vitamin D supplementation. SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 19 March 2020. We also searched database such as PubMed, clinical trial registries and the reference lists of relevant articles and reviews. Date of last search: 14 January 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing oral administration of any form of vitamin D supplementation at any dose and for any duration to another type or dose of vitamin D or placebo or no supplementation in people with SCD, of all ages, gender, and phenotypes. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data and assessed the risk of bias of the included studies. They used the GRADE guidelines to assess the quality of the evidence. MAIN RESULTS: Vitamin D versus placebo One double-blind RCT (n = 39) compared oral vitamin D3 (cholecalciferol) supplementation (20 participants) to placebo (19 participants) for six weeks. Only 25 participants completed the full six months of follow-up. The study had a high risk of bias due to incomplete outcome data, but a low risk of bias for randomisation, allocation concealment, blinding (of participants, personnel and outcome assessors) and selective outcome reporting; and an unclear risk of other biases. Vitamin D supplementation probably led to higher serum 25(OH)D levels at eight weeks, mean difference (MD) 29.79 (95% confidence interval (CI) 26.63 to 32.95); at 16 weeks, MD 12.67 (95% CI 10.43 to 14.90); and at 24 weeks, MD 15.52 (95% CI 13.50 to 17.54) (moderate-quality evidence). There was little or no difference in adverse events (tingling of lips or hands) between the vitamin D and placebo groups, risk ratio 3.16 (95% CI 0.14 to 72.84) (low-quality evidence). Vitamin D supplementation probably caused fewer pain days compared to the placebo group at eight weeks, MD -10.00 (95% CI -16.47 to -3.53) (low-quality evidence), but probably led to a lower (worse) health-related quality of life score (change from baseline in physical functioning PedsQL scores); at both 16 weeks, MD -12.56 (95% CI -16.44 to -8.69) and 24 weeks, MD -12.59 (95% CI -17.43 to -7.76), although this may not be the case at eight weeks (low-quality evidence). Vitamin D supplementation regimens compared Two double-blind RCTs (83 participants) compared different regimens of vitamin D. One RCT (n = 62) compared oral vitamin D3 7000 IU/day to 4000 IU/day for 12 weeks, while the second RCT (n = 21) compared oral vitamin D3 100,000 IU/month to 12,000 IU/month for 24 months. Both RCTs had low risk of bias for blinding (of participants, personnel and outcome assessors) and incomplete outcome data, but the risk of selective outcome reporting bias was high. The bias from randomisation and allocation concealment was low in one study but not in the second. There was an unclear risk of other biases. When comparing oral vitamin D 100,000 IU/month to 12,000 IU/month, the higher dose may have resulted in higher serum 25(OH)D levels at one year, MD 16.40 (95% CI 12.59 to 20.21) and at two years, MD 18.96 (95% CI 15.20 to 22.72) (low-quality evidence). There was little or no difference in adverse events between doses (low-quality evidence). There were more episodes of acute chest syndrome in the high-dose group, at one year, MD 0.27 (95% CI 0.02 to 0.52) but there was little or no difference at two years, MD 0.09 (95% CI -0.04 to 0.22) (moderate-quality evidence). At one year and two years there was also little or no difference between the doses in the presence of pain (moderate-quality evidence) or forced expiratory volume in one second % predicted. However, the high-dose group had lower values for % predicted forced vital capacity at both one and two years, MD -7.20% predicted (95% CI -14.15 to -0.25) and MD -7.10% predicted (95% CI -14.03 to -0.17), respectively. There were little or no differences between dose regimens in the muscle health of either hand or the dominant hand. The study comparing oral vitamin D3 7000 IU/day to 4000 IU/day (21 participants) did not provide data for analysis, but median serum 25(OH)D levels were reported to be lower in the low-dose group at both six and 12 weeks. At 12 weeks the median serum parathyroid hormone level was lower in the high-dose group. AUTHORS' CONCLUSIONS: We included three RCTs of varying quality. We consider that the current evidence presented in this review is not of sufficient quality to guide clinical practice. Until further evidence becomes available, clinicians should consider the relevant existing guidelines for vitamin D supplementation and dietary reference intakes for calcium and vitamin D. Well-designed RCTs of parallel design, are required to determine the effects and the safety of vitamin D supplementation as well as to assess the relative benefits of different doses in children and adults with SCD.


Assuntos
Anemia Falciforme/sangue , Anemia Falciforme/complicações , Colecalciferol/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/administração & dosagem , Administração Oral , Viés , Criança , Colecalciferol/efeitos adversos , Humanos , Dor/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Vitamina D/efeitos adversos , Vitamina D/sangue , Deficiência de Vitamina D/terapia
15.
PLoS One ; 15(4): e0229959, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32243480

RESUMO

Sickle cell disease (SCD) is characterized by deoxygenation-induced polymerization of hemoglobin in red blood cells, leading to hemolytic anemia, vaso-occlusion, and the development of multiple clinical complications. To characterize the clinical burden associated with differences in hemoglobin concentration and hemolysis measures, a systematic literature review of MEDLINE, EMBASE, and related meta-analyses was undertaken. For quantitative analyses related to hemoglobin concentration, pooled results were analyzed using random effects models to control for within-and between-study variability. To derive risk ratios associated with hemoglobin concentration change, we combined ratios of means from select studies, which reported hazard and odds ratios in meta-analyses for hemoglobin concentration-related outcomes and changes between groups. Forty-one studies were identified for inclusion based on relating hemoglobin concentration to clinical outcomes. Meta-analyses demonstrated that mean hemoglobin concentration was significantly lower in patients with cerebrovascular disease (0.4 g/dL), increased transcranial Doppler velocity in cerebral arteries (0.6 g/dL), albuminuria (0.6 g/dL), elevated estimated pulmonary artery systolic pressure (0.9 g/dL), and in patients that subsequently died (0.6 g/dL). In a risk reduction meta-analysis, modeled increased hemoglobin concentrations of 1 g/dL or greater resulted in decreased risk of negative clinical outcomes of 41% to 64%. In conclusion, chronic anemia is associated with worse clinical outcomes in individuals with SCD and even modest increases in hemoglobin concentration may be beneficial in this patient population. This systematic review has been registered on Prospero (Registration number CRD42018096860; https://www.crd.york.ac.uk/prospero/).


Assuntos
Anemia Falciforme/sangue , Transtornos Cerebrovasculares/sangue , Hemoglobinas/metabolismo , Nefropatias/sangue , Anemia/sangue , Anemia/epidemiologia , Anemia/patologia , Anemia Falciforme/mortalidade , Anemia Falciforme/patologia , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/patologia , Hemoglobina Falciforme/genética , Hemoglobina Falciforme/metabolismo , Hemólise , Humanos , Nefropatias/epidemiologia , Nefropatias/patologia , Razão de Chances , Ultrassonografia Doppler Transcraniana
16.
PLoS One ; 15(4): e0218880, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32267841

RESUMO

People with sickle cell disease (SCD) are reported to have low rates of HIV infection, slower progression to AIDS and lower HIV-associated mortality compared to the general population. Mechanisms of potential resistance to HIV in SCD are incompletely understood. We retrospectively reviewed the Transfusion Safety Study to compare HIV status between people with SCD and other congenital anemias who were routinely exposed to blood products during the high-risk period before HIV screening implementation. Non-SCD congenital anemia diagnosis was associated with a higher risk of HIV acquisition compared to SCD (OR 13.1 95%CI 1.6-108.9). In addition, we prospectively enrolled 30 SCD cases and 30 non-SCD controls to investigate potential mechanisms of resistance to HIV in SCD. CCR5 and CCR7 expression was lower and CD4 expression was higher on CD4+ T cells from SCD cases compared to controls. Surface expression of CD4+ T cell CXCR4, CD38 and HLA-DR did not differ between the groups. SCD CD4+ T cells were not less susceptible to HIV infection than controls. Levels of multiple cytokines were elevated in the SCD plasma, but SCD plasma compared to control plasma did not inhibit HIV infection of target cells. In conclusion, our epidemiological data support people with SCD being resistant to HIV infection. Potential mechanisms include lower CD4+ T cell expression of CCR5 and CCR7, balanced by increased CD4 expression and cytokine levels, which did not result in in vitro resistance to HIV infection. Further study is needed to define the risk and pathophysiology of HIV in persons with SCD.


Assuntos
Anemia Falciforme/terapia , Segurança do Sangue/efeitos adversos , Infecções por HIV/etiologia , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/imunologia , Transfusão de Sangue , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular , Citocinas/sangue , Citocinas/imunologia , Suscetibilidade a Doenças , Feminino , HIV/isolamento & purificação , Infecções por HIV/sangue , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Reação Transfusional , Adulto Jovem
17.
Am J Hematol ; 95(7): 766-774, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32243618

RESUMO

In the US, mortality in sickle cell disease (SCD) increases after age 18-20 years. Biomarkers of mortality risk can identify patients who need intensive follow-up and early or novel interventions. We prospectively enrolled 510 SCD patients aged 3-20 years into an observational study in 2006-2010 and followed 497 patients for a median of 88 months (range 1-105). We hypothesized that elevated pulmonary artery systolic pressure as reflected in tricuspid regurgitation velocity (TRV) would be associated with mortality. Estimated survival to 18 years was 99% and to 25 years, 94%. Causes of death were known in seven of 10 patients: stroke in four (hemorrhagic two, infarctive one, unspecified one), multiorgan failure one, parvovirus B19 infection one, sudden death one. Baseline TRV ≥2.7 m/second (>2 SD above the mean in age-matched and gender-matched non-SCD controls) was observed in 20.0% of patients who died vs 4.6% of those who survived (P = .012 by the log rank test for equality of survival). The baseline variable most strongly associated with an elevated TRV was a high hemolytic rate. Additional biomarkers associated with mortality were ferritin ≥2000 µg/L (observed in 60% of patients who died vs 7.8% of survivors, P < .001), forced expiratory volume in 1 minute to forced vital capacity ratio (FEV1/FVC) <0.80 (71.4% of patients who died vs 18.8% of survivors, P < .001), and neutrophil count ≥10x109 /L (30.0% of patients who died vs 7.9% of survivors, P = .018). In SCD children, adolescents and young adults, steady-state elevations of TRV, ferritin and neutrophils and a low FEV1/FVC ratio may be biomarkers associated with increased risk of death.


Assuntos
Anemia Falciforme , Insuficiência da Valva Tricúspide , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Anemia Falciforme/mortalidade , Anemia Falciforme/fisiopatologia , Biomarcadores/sangue , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Ferritinas/sangue , Seguimentos , Humanos , Contagem de Leucócitos , Masculino , Neutrófilos , Estudos Prospectivos , Taxa de Sobrevida , Insuficiência da Valva Tricúspide/sangue , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/mortalidade , Insuficiência da Valva Tricúspide/fisiopatologia , Estados Unidos/epidemiologia , Adulto Jovem
19.
Ann Hematol ; 99(5): 937-945, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32166377

RESUMO

Hydroxyurea (HU) is used as a therapy in sickle cell anemia (SCA). Many studies have established that HU improves patient quality of life by reducing symptoms. However, the effect of HU on erythrocytes is not well-described. We evaluated several parameters related to oxidative stress and total lipid content of erythrocytes in patients with SCA. The patient cohort consisted of 7 SCA patients treated with HU, 17 untreated SCA patients, and 15 healthy subjects. Erythrocytes from patients with SCA displayed increased oxidative stress relative to the control group, including higher thiobarbituric acid reactive substances (TBARS), Fe3+ content, and osmotic fragility, and decreased total cholesterol. We observed that treatment of SCA patients with HU increased Fe3+ content and activity of glutathione peroxidase, and decreased glutathione reductase activity, glutathione levels, total cholesterol, and phospholipid content comaperaded to patients untreated with HU. Thus, HU alters biochemical characteristics of erythrocytes; future studies will determine whether they are beneficial or not.


Assuntos
Anemia Falciforme , Eritrócitos Anormais/metabolismo , Hidroxiureia/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Colesterol/sangue , Feminino , Humanos , Masculino , Fragilidade Osmótica/efeitos dos fármacos , Fosfolipídeos/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
20.
Ann Hematol ; 99(5): 947-953, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32140892

RESUMO

Sickle cell anemia (SCA) pathophysiology is characterized by the activation of sickle red blood cells, reticulocytes, leukocytes, platelets, and endothelial cells, and with the expression of several inflammatory molecules. Therefore, it is conceivable that variations in levels of proinflammatory cytokines may act as a signaling of differential clinical course in SCA. Here, we evaluated the clinical impact of proinflammatory cytokines interleukin 1-ß (IL-1ß), interleukin 6 (IL-6), and interleukin 8 (IL-8) in 79 patients with SCA, followed in a single reference center from northeastern Brazil. The main clinical/laboratory data were obtained from patient interview and medical records. The proinflammatory markers IL-1ß, IL-6, and IL-8 were evaluated by using commercially available enzyme-linked immunosorbent assay kits. According to levels of the proinflammatory markers, we observed that patients who had a higher frequency of VOC per year (P = 0.0236), acute chest syndrome (P = 0.01), leg ulcers (P = 0.0001), osteonecrosis (P = 0.0006), stroke (P = 0.0486), and priapism (P = 0.0347) had higher IL-6 levels compared with patients without these clinical complications. Furthermore, increased levels of IL-8 were found in patients who presented leg ulcers (P = 0.0184). No significant difference was found for IL-1ß levels (P > 0.05). In summary, the present study emphasizes the role of inflammation in SCA pathophysiology, reveals an association of IL-8 levels and leg ulcer occurrence, and indicates that IL-6 levels can be used as a useful predictor for poor outcomes in SCA.


Assuntos
Anemia Falciforme/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Úlcera da Perna/sangue , Adulto , Anemia Falciforme/epidemiologia , Brasil , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Interleucina-1beta/sangue , Úlcera da Perna/epidemiologia , Masculino , Pessoa de Meia-Idade
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