Role of paraoxonase 1 activity and PON1 gene polymorphisms in sickle cell disease.

Sickle cell disease (SCD) patients often exhibit a dyslipidemic sub-phenotype. Paraoxonase 1 (PON 1) is a serum glycoprotein associated with the high-density lipoproteins cholesterol (HDL-C), and variability in PON1 activity depends on the PON1 genotypes. We investigated the influence of PON1c.192Q > R and PON1c.55L > M polymorphisms on PON1 activity and laboratory parameters and the association between PON1 activity and clinical manifestations in SCD patients. We recruited 350 individuals, including 154 SCD patients and 196 healthy volunteers, which comprised the control group. Laboratory parameters and molecular analyses were investigated from the participants' blood samples. We have found increased PON1 activity in SCD individuals compared to the control group. In addition, carriers of the variant genotype of each polymorphism presented lower PON1 activity. SCD individuals carrying the variant genotype of PON1c.55L > M polymorphism had lower platelet and reticulocyte counts, C-reactive protein, and aspartate aminotransferase levels; in addition to higher creatinine levels. SCD individuals carrying the variant genotype of PON1c.192Q > R polymorphism had lower triglyceride, VLDL-c, and indirect bilirubin levels. Furthermore, we observed an association between PON1 activity history of stroke and splenectomy. The present study confirmed the association between PON1c.192Q > R and PON1c.55L > M polymorphisms and PON1 activity, in addition to demonstrate their effects on markers of dislipidemia, hemolysis and inflammation, in SCD individuals. Moreover, data suggest PON1 activity as a potential biomarker related to stroke and splenectomy.

Association of laboratory markers and cerebral blood flow among sickle cell anemia children.

Background: Stroke is one of the highest complications of sickle-cell anemia (SCA). The Transcranial Doppler (TCD) has been adopted worldwide as a gold standard method for detecting alterations in the blood velocity in cerebral arteries. In this study, we investigated the association between laboratory parameters and increased cerebral blood flow velocity in Brazilian SCA pediatric patients. Methods: The study included 159 pediatric patients with SCA, submitted to TCD velocity screening, and the time-averaged maximum mean velocity (TAMMV) was determined in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and distal intracranial internal carotid artery (ICA). We compared cerebral blood flow in patients stratified by the following: TCD1-defined as normal, with TAMMV inferior to 170 cm/s; TCD2-conditional, with TAMMV above 170 cm/s, but less than 199 cm/s; TCD3-altered, with TAMMV greater than or equal to 200 cm/s. Results: TAMMV was negatively correlated with age and weight (p < 0.05). Moreover, TAMMV was associated or correlated with reductions in HbF, RBC, hemoglobin, hematocrit, HDL, and haptoglobin and, increases in MCV, MCH, RDW, reticulocytes, WBC, lymphocytes, monocytes, eosinophils, total and indirect bilirubin, LDH, AST, ALT, glucose, ferritin, and AAT (p < 0.05). Conclusion: The current study highlights the importance of the investigation of hemolytic and inflammatory biomarkers for monitoring the clinical outcome of SCA pediatric patients, to avoid acute or chronic stroke. Moreover, glucose and HDL-C appear useful for predicting higher TAMMV.

Prevalence of clinical manifestations suggestive of depression in patients with sickle cell disease: a review / Prevalência de manifestações clínicas sugestivas de depressão em pacientes portadores de doença falciforme: uma revisão

OBJECTIVE: To assess the prevalence of clinical manifestations suggestive of depression in patients with sickle cell disease. METHODS: A systematic search was performed in the electronic databases PubMed® , LILACS and SciELO, with the following inclusion criteria: cross-sectional studies that assessed the prevalence of depression in patients with sickle cell disease, published in English or Portuguese in the last 10 years. The selection of the articles was performed in two stages by two independent researchers following the PRISMA (Preferred reporting items for systematic reviews and meta-analyses) recommendations. The first stage consisted on screening the titles and abstracts, and in the second stage the full text was appraised, both following the pre-defined inclusion and exclusion criteria. RESULTS: From the 42 articles available, nine were included in this review. Seven instruments were used to screen for depression with different cutoff points, and the Patient Health Questionnaire-9 (PHQ-9) was the most used instrument. The worldwide prevalence of clinical manifestations suggestive of depression ranged from 11 to 40%, according to several variables. CONCLUSION: The prevalence of clinical manifestations suggestive of depression in patients with sickle cell disease is higher compared to the prevalence of depression in the general population. Thus, the multidisciplinary follow-up for these people, with a focus on mental health, is of great importance.

OBJETIVO: Avaliar a prevalência mundial de manifestações clínicas sugestivas de depressão em portadores de doença falciforme. MÉTODOS: Realizou-se uma busca sistemática nas bases de dados eletrônicas PubMed® , LILACS e SciELO, para identificação dos estudos transversais, publicados em inglês ou português nos últimos 10 anos, que avaliaram a prevalência de depressão em portadores de doença falciforme. A seleção dos artigos foi realizada em duas etapas e por dois pesquisadores independentes seguindo a recomendação PRISMA (Preferred reporting items for systematic reviews and meta-analyses). A primeira etapa consistiu na triagem dos títulos e resumos e na segunda etapa foi realizada a análise completa do artigo, ambas seguindo os critérios de inclusão e exclusão predefinidos. RESULTADOS: Dos 42 artigos disponíveis, nove foram incluídos na revisão. Foram utilizados sete instrumentos diferentes para rastreio de depressão com diferentes pontos de corte, sendo The Patient Health Questionnaire-9 (PHQ-9) o instrumento mais utilizado. A prevalência mundial de manifestações clínicas sugestivas de depressão variou de 11% a 40%, conforme diversas variáveis verificadas. CONCLUSÃO: A prevalência de manifestações clínicas sugestivas de depressão encontrada para os portadores de doença falciforme é superior à prevalência de depressão descrita na população geral. Desse modo, é de suma importância o acompanhamento multidisciplinar para essas pessoas, com enfoque na saúde mental.

Priapism in sickle cell disease: Associations between NOS3 and EDN1 genetic polymorphisms and laboratory biomarkers.

Priapism is a urologic emergency characterized by an uncontrolled, persistent and painful erection in the absence of sexual stimulation, which can lead to penile fibrosis and impotence. It is highly frequent in sickle cell disease (SCD) associated with hemolytic episodes. Our aim was to investigate molecules that may participate in the regulation of vascular tone. Eighty eight individuals with SCD were included, of whom thirty-seven reported a history of priapism. Priapism was found to be associated with alterations in laboratory biomarkers, as well as lower levels of HbF. Patients with sickle cell anemia using hydroxyurea and those who received blood products seemed to be less affected by priapism. Multivariate analysis suggested that low HbF and NOm were independently associated with priapism. The frequency of polymorphisms in genes NOS3 and EDN1 was not statistically significant between the studied groups, and the presence of the variant allele was not associated with alterations in NOm and ET-1 levels in patients with SCD. The presence of the variant allele in the polymorphisms investigated did not reveal any influence on the occurrence priapism. Future studies involving larger samples, as well as investigations including patients in priapism crisis, could contribute to an enhanced understanding of the development of priapism in SCD.

An evaluation of ticagrelor for the treatment of sickle cell anemia.

INTRODUCTION: Ticagrelor is an antiplatelet agent approved for the treatment of patients with an acute coronary syndrome or a history of myocardial infarction. Considering the evidence demonstrating that ticagrelor-mediated inhibition of platelet activation and aggregation have beneficial effects in the treatment of thrombotic conditions, clinical studies have been conducted to evaluate the use of this drug for the treatment of sickle cell disease (SCD), demonstrating satisfactory tolerability and safety. AREAS COVERED: Clinical investigation has characterized the pharmacokinetic and pharmacodynamical profile, as well as the efficacy and safety of ticagrelor to prevent painful vaso-occlusive crisis (painful episodes and acute chest syndrome) in SCD patients. EXPERT OPINION: While phase 1 and 2 clinical trials demonstrated satisfactory tolerability and safety, the conclusion of phase 3 clinical trials is crucial to prove the efficacy of ticagrelor as a therapeutic option for the treatment of SCD. Thus, it is expected that ticagrelor, especially in combination with other drugs, will improve the clinical profile and quality of life of patients with SCD.

Effect of N(Epsilon)-(carboxymethyl)lysine on Laboratory Parameters and Its Association with ß S Haplotype in Children with Sickle Cell Anemia.

The present study aimed to investigate the association of N ε -carboxymethyllysine (CML) with laboratory parameters and ß S haplotypes in pediatric sickle cell anemia (SCA) patients with or without hydroxyurea (HU) therapy. We included 55 children with SCA (SCAtotal), where 27 were on HU treatment (SCA-HU+) and 28 without HU treatment (SCA-HU-). Laboratory characteristics were determined using electronic methods while CML was measured using competitive ELISA. ß S haplotypes were determined by RFLP-PCR. Significant increases in MCV and MCH and significant decreases in leukocytes, eosinophils, basophils, atypical lymphocytes, lymphocytes, and monocytes were found in SCA-HU+ compared to SCA-HU-. SCA-HU+ presented significant reduction in aspartate transaminase and lactate dehydrogenase and increase in creatinine levels compared to SCA-HU-. CML levels were significantly higher in both SCA-HU+ and SCA-HU- compared to the healthy control. In addition, a negative correlation was found between CML and alanine transaminase in SCA-HU+ and SCAtotal (p < 0.01). A significant association was found between CML levels and ß S haplotypes. The results suggest that CML has a role to play in SCA complications, independent of HU therapy.

Hydroxyurea alters hematological, biochemical and inflammatory biomarkers in Brazilian children with SCA: Investigating associations with ßS haplotype and α-thalassemia.

This study investigated the effects of hydroxyurea (HU) on hematological, biochemical and inflammatory parameters in children with sickle cell anemia (SCA) in association with ßS haplotype and α-thalassemia. We included 22 children with SCA who were followed for an average of 14.5 months. Laboratory parameters were assessed by electronic methods, and molecular analysis was investigated by PCR-RFLP and allele-specific PCR. Results showed significant increases in hemoglobin, HbF, hematocrit, MCV, MCH, glucose, HDL-C and albumin levels, as well as significant decreases in MCHC and AST levels, WBC, neutrophils, eosinophils, lymphocytes and reticulocytes, in children during HU therapy. HbF levels were positively correlated with hemoglobin, hematocrit, MCV and total protein, yet negatively correlated with MCHC, RDW, AAT and AST during HU therapy (p<0.05). Children who carried the Central African Republic haplotype, in response to HU therapy, presented significant increases in hemoglobin, hematocrit, triglycerides and uric acid levels, as well as significant decreases in MCHC, AST and direct bilirubin levels, WBC, neutrophils, eosinophils, lymphocytes and reticulocytes. Those with the Benin haplotype presented increases in HbF and albumin levels, and a reduction in platelet counts (p<0.05). Children with α-thalassemia presented decreased ALT during HU use, while those without this deletion presented increases in hemoglobin, hematocrit, MCV, MCH, HDL-C and albumin, as well as decreases in MCHC, neutrophils, lymphocytes, reticulocytes and AST (p<0.05). Hence, regardless of its use in association with ßS haplotypes or α-thalassemia, HU seems to be linked to alterations in hemolytic, inflammatory, hepatic, lipid and glycemic profiles.

Hidden hearing loss in children and adolescents with sickle cell anemia.

OBJECTIVE: To evaluate the auditory system for hidden hearing loss (HHL) and its association with clinical variables and endothelial dysfunction (ED) in children and adolescents with sickle cell anemia (SCA). METHODS: Participants included 37 patients with stable SCA and 44 healthy controls (HC group) (aged 6-18 years) with hearing thresholds ≤ 20 dB (dB) were evaluated for pure tone audiometry, tympanometry, acoustic reflex, otoacoustic emission, and auditory evoked potentials. Laboratory analysis of the lipid profile, and C-reactive protein levels and endothelial function using ultrasonographic imaging of the brachial artery to assess flow-mediated dilation were performed. RESULTS: The SCA group presented with a higher rate of increased contralateral acoustic reflex thresholds, compared to those in the HC group at all frequencies and in both ears (p < 0.05). There were significant differences in the brainstem auditory evoked potentials between the SCA and HC groups. In the SCA group, the waves III and V latencies were increased (p = 0.006 and 0.004 respectively), and the I-III and I-V interpeak intervals were longer (p = 0.015 and 0.018 respectively) than those in the HC group. There was no association between the audiological measures and clinical and metabolic variables and sickle cell anemia complications including endothelial function and therapy. CONCLUSION: In conclusion, our findings suggest that damage in the auditory system in SCA patients can be present involving retrocochlear structures, causing functional deficits without deterioration of auditory sensitivity.

Sensorineural hearing loss in children with sickle cell anemia and its association with endothelial dysfunction.

OBJECTIVES: To investigate the prevalence of sensorineural hearing loss (SNHL) in children and adolescents with sickle cell anemia (SCA) and its association with endothelial dysfunction (ED). METHODS: Fifty-two participants with stable SCA and 44 apparently healthy (AA genotype) participants aged 6-18 years were evaluated for pure tone audiometry and endothelial function using ultrasonographic imaging of the brachial artery to assess flow-mediated dilation (FMD). Laboratory analysis of the lipid profile and C-reactive protein levels was performed. RESULTS: In the SCA group, 15 (28.8%) patients presented with SNHL. The FMD values were reduced in the SCA with SNHL group compared with the SCA without SNHL and healthy groups. Logistic regression analysis showed that FMD was associated with SNHL independent of the lipid profile and SCA characteristics (odds ratio [95% confidence interval] = 0.614 [0.440-0.858]; p = 0.004). DISCUSSION: SNHL is a common complication in SCA; furthermore, this study identified a significant association between ED and SNHL. Damage to the vascular endothelium because of inflammation in SCA reduced blood flow in the inner ear. Thus, this circulatory disorder culminates in vaso-occlusive process and induces auditory disorders, such as SNHL.

Associations between endothelial dysfunction and clinical and laboratory parameters in children and adolescents with sickle cell anemia.

BACKGROUND: Hematological changes can drive damage of endothelial cells, which potentially lead to an early endothelial dysfunction in patients with sickle cell anemia (SCA). An association may exist between endothelial dysfunction and several clinical manifestations of SCA. The present study aims to evaluate the links between changes in endothelial function and clinical and laboratory parameters in children and adolescents with SCA. METHODS: This study included 40 children and adolescents with stable SCA as well as 25 healthy children; aged 6-18 years. All study subjects were evaluated for endothelial function using Doppler ultrasonography. In addition, a number of laboratory assays were performed, including reticulocyte and leukocyte counts as well as measurement of circulating levels of total bilirubin, C-reactive protein (CRP), glucose, lipoproteins and peripheral oxyhemoglobin saturation. These parameters were also compared between SCA patients who were undertaking hydroxyurea (HU) and those who were not. RESULTS: Flow-mediated vasodilation (FMD) values were found to be reduced in SCA patients compared with those detected in healthy controls. SCA individuals with lower FMD values exhibited higher number of hospital admissions due to vaso-occlusive events. Additional analyses revealed that patients who had decreased FMD values exhibited higher odds of acute chest syndrome (ACS) episodes. A preliminary analysis with limited number of individuals failed to demonstrate significant differences in FMD values between SCA individuals who were treated with HU and those who were not. CONCLUSIONS: Children and adolescents with SCA exhibit impaired endothelial function. Reductions in FMD values are associated with ACS. These findings underline the potential use of FMD as screening strategy of SCA patients with severe prognosis at early stages.

Laboratory and Genetic Biomarkers Associated with Cerebral Blood Flow Velocity in Hemoglobin SC Disease.

Reference values for cerebral blood flow velocity (CBFV) in hemoglobin SC disease (HbSC) have not been established. We aimed to investigate associations between laboratory and genetic biomarkers associated with CBFV in HbSC children. Sixty-eight HbSC children were included; CBFV was analyzed by transcranial Doppler, and the time-averaged maximum mean velocity (TAMMV) was estimated. Hematological, biochemical, immunological, and genetic analyses were performed. TAMMV was negatively correlated with red blood cell count (RBC) count, hemoglobin, hematocrit, and direct bilirubin (DB), yet positively correlated with monocytes and ferritin. We found that children with TAMMV ≥ 128 cm/s had decreased red blood cell distribution width (RDW) and nitric oxide metabolite (NOx) concentration. Children with TAMMV ≥ 143.50 cm/s had decreased hemoglobin and hematocrit, as well as increased ferritin levels. Decreased hemoglobin, hematocrit, RDW, and NOx and increased ferritin were detected in children with TAMMV ≥ 125.75 cm/s. The CAR haplotype was associated with higher TAMMV. In association analyses, RBC, hemoglobin, hematocrit, RDW, monocyte, DB, NOx, and ferritin, as well as the CAR haplotype, were found to be associated with higher TAMMV in HbSC children. Multivariate analysis suggested that high TAMMV was independently associated with hematocrit, RDW, and NOx. Additional studies are warranted to validate the establishment of a cutoff value of 125.75 cm/s associated with elevated TAMMV in HbSC children.

Heme-mediated cell activation: the inflammatory puzzle of sickle cell anemia.

INTRODUCTION: Hemolysis triggers the onset of several clinical manifestations of sickle cell anemia (SCA). During hemolysis, heme, which is derived from hemoglobin (Hb), accumulates due to the inability of detoxification systems to scavenge sufficiently. Heme exerts multiple harmful effects, including leukocyte activation and migration, enhanced adhesion molecule expression by endothelial cells and the production of pro-oxidant molecules. Area covered: In this review, we describe the effects of heme on leukocytes and endothelial cells, as well as the features of vascular endothelial cells related to vaso-occlusion in SCA. Expert commentary: Free Hb, heme and iron, potent cytotoxic intravascular molecules released during hemolysis, can exacerbate, modulate and maintain the inflammatory response, a main feature of SCA. Endothelial cells in the vascular environment, as well as leukocytes, can become activated via the molecular signaling effects of heme. Due to the hemolytic nature of SCA, hemolysis represents an interesting therapeutic target for heme-scavenging purposes.

The DAU Allele and Anti-D Alloimmunization Present With High Frequency in Brazilian Sickle Cell Disease Patients.

BACKGROUND: Antigens DIIIa, DAR and DAU are common in people of African descent and are involved in anti-D alloimmunization. Sickle cell disease (SCD) patients frequently need blood therapy and are vulnerable to alloimmunization. METHODS: The study included SCD patients from the Brazilian state of Bahia, which has the highest incidence of the disease in Brazil; 241 SCD patients and 220 healthy individuals were studied. Alleles were characterized by PCR-RFLP and PCR-SSP techniques. RESULTS: The DAU allele was found in 22.3% (43/193) of the SCD patients. Two (1%) patients had the DIIIa/D wild-type genotype, one (0.5%) had the DIIIa/D- genotype, 11 (5.7%) had the DAR/D wild-type genotype and three (1.6%) had the DAR/D- genotype. Two patients were positive for the 667T>G mutation and the 1136C>T mutation, one (0.5%) had the genotype DIIIa/DAU, and one (0.5%) had the genotype DAR/DAU. CONCLUSION: There was statistical significance when the allele frequencies were evaluated among SCD, sickle cell anemia (HbSS) patients and healthy individuals. The frequencies of the DIIIa, DAR and DAU alleles among SCD patients differ from those of healthy individuals from the same population, and a high frequency of the DAU variant was associated with anti-D alloimmunization in these patients.

Transcranial Doppler in hemoglobin SC disease.

BACKGROUND: Stroke is a severe clinical disorder in sickle cell disease (SCD), and few studies have evaluated transcranial Doppler (TCD) flow velocities in hemoglobin SC disease (HbSC). The guidelines for stroke risk are based on evaluations in sickle cell anemia (SCA) or HbS/ß thalassemia. PROCEDURE: In this study, we compare cerebral blood flow in patients with SCD stratified by genotypes. A total of 1,664 pediatric patients with SCD underwent TCD velocity screening, and the time-averaged maximum mean velocity (TAMM) was determined in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and distal intracranial internal carotid artery (ICA). RESULTS: Abnormal velocities were not identified in the ACA; therefore, we only use ICA and MCA velocities. TAMM from the left and right in the ICA and MCA was 134.3 ± 32.0 and 134.4 ± 32.6 cm/s in patients with SCA, and 105.2 ± 20.6 and 104.7 ± 20.0 cm/s in the patients with HbSC, respectively. Mean TAMM between right and left ICA/MCA was 134.5 ± 30.5 cm/s in the SCA group, and 104.9 ± 19.3 cm/s in the HbSC group. Notably, our data show that TCD velocities were significantly lower among the patients with HbSC compared to SCA. TAMM was negatively correlated with hemoglobin and hematocrit in both genotypes. CONCLUSION: These results suggest that a different cut-off value for abnormal TCD velocities could be considered for patients with HbSC. Additional studies are warranted to determine the actual risk of stroke in HbSC genotype associated with this possible TCD risk value.

The association of infection and clinical severity in sickle cell anaemia patients.

Sickle cell anaemia (SCA) patients have a high risk of infection. We retrospectively investigated the prevalence of infection among SCA patients from Bahia, Brazil. A total of 1415 SCA patients were studied between 1995 and 2009: 190 (13.4%) had hepatitis C virus (HCV), 67 (4.7%) had human T-lymphotropic virus type I (HTLV-I), 44 (3.1%) had hepatitis B virus (HBV), 40 (2.8%) had Chagas' disease, 11 (0.8%) had human immunodeficiency virus (HIV), and 5 (0.4%) had syphilis. Patients with HCV infection had a higher risk of hospitalisation (OR=1.52, 95% Cl: 1.07-2.17, P=0.020), bone disorders (OR=1.94, 95% Cl: 1.15-3.27, P=0.011), stroke (OR=2.17, 95% Cl: 1.12-4.14, P=0.017), painful crisis (OR=1.61, 95% Cl: 1.17-2.22, P=0.004) and leg ulcers (OR=1.61, 95% Cl: 1.04-3.03, P=0.031). Patients with HBV infection had a higher risk for bone disorders (OR=4.90, 95% Cl: 2.08-11.54, P<.010), stroke (OR=3.01, 95% Cl: 1.29-6.04, P=0.007), painful crisis (OR=3.51, 95% Cl: 1.62-7.63, P<0.001), acute chest syndrome (ACS) (OR=2.66, 95% Cl: 1.34-5.28, P=0.004), leg ulcers (OR=6.60, 95% Cl: 3.37-12.91, P<.001) and vaso-occlusive crisis (OR=6.34, 95% Cl: 1.96-20.66, P<0.001). Patients with HTLV-I infection had a high risk for bone disorders (OR=2.94, 95% Cl: 1.28-6.74, P=0.011), respiratory failure (OR=2.66, 95% Cl: 1.26-5.51, P=0.012), leg ulcers (OR=3.27, 95% Cl: 1.69-6.11, P<.001), painful crisis (OR=1.82, 95% Cl: 1.07-3.13, P=0.025) and ACS (OR=1.85, 95% Cl: 1.10-3.41, P<.047). SCA patients with HCV infection had increased triglycerides and low-density lipoprotein cholesterol (P=0.036; P=0.027), iron serum (P=0.016) and ferritin (P=0.007). These results reveal important roles for these infections in SCA patients' clinical outcomes, and studies are warranted to determine the mechanisms utilised by these agents and their involvement in disease severity.

Ocular lesions in sickle cell disease patients from Bahia, Brazil / Lesões oculares em pacientes com doença falciforme da Bahia, Brasil

OBJECTIVE: The present study aims to describe ocular alterations in sickle cell disease patients in Bahia, a Northeast state, with the highest prevalence of the disease in Brazil. METHODS: We carried out a cross-sectional study in a group of 146 (292 eyes) sickle cell disease patients (90 HBSS and 56 HBSC). Ophthalmologic examination including indirect binocular ophthalmoscopy was performed. Examination was completed by fluorescein angiography to detect retinal lesions. RESULTS: The most frequent ocular lesions identified were "vascular tortuosity" and "black sunburst". Proliferative retinopathy was found in 22 (12.2 percent) eyes of HBSS patients and 25 (22.3 percent) eyes of HBSC patients (OR=2.06; CI95 percent: 1.5-4.06, p=0.022); Its frequency was higher among HBSS patients aged 20-39 years, while in HBSC patients, it peaked after 40 years (35.7 percent and 42.8 percent) and dropped sharply afterwards. CONCLUSION: Proliferative retinopathy was described as early as 10 years of age in both patients groups. Proliferative sickle retinopathy can result in blindness and the knowledge of the most prevalent ocular alterations and age risk will be important to establish a protocol of ophthalmologic follow-up, in order to prevent a severe visual loss and increase patient's life quality.

OBJETIVO: O presente estudo teve como objetivo descrever as alterações oculares em pacientes portadores de doença falciforme, na Bahia, um estado do Nordeste, que tem a maior prevalência da doença no Brasil. MÉTODOS: Nós conduzimos um estudo de corte transversal em um grupo de 146 (292 olhos) pacientes com Doença Falciforme (90 HBSS e 56 HBSC). Para exame oftalmológico foi realizada oftalmoscopia binocular indireta complementada pela retinografia fluorescente para detecção de lesões retinianas decorrentes da Doença Falciforme. RESULTADOS: As lesões mais frequentemente encontradas foram o aumento da tortuosidade vascular e "black sumburst" Retinopatia proliferativa foi encontrada em 22 (12,2 por cento) olhos de pacientes HBSS e 25 (22,3 por cento) olhos de pacientes HBSC (OR=2.06; CI95 por cento: 1.5-4.06, p=0. 022); essa frequência foi maior entre os pacientes HBSS com idade entre 20 - 39 anos, enquanto que nos pacientes HBSC foi maior nos acima de 40 anos (35.7 por cento e 42.8 por cento), decaindo abruptamente após essa idade. CONCLUSÃO: Retinopatia proliferativa foi descrita por volta dos dez anos de idade em ambos os grupos. A prevalência da retinopatia falciforme proliferativa pode resultar em cegueira e o conhecimento das alterações oculares mais prevalentes e idade de risco destas em pacientes com Doença Falciforme será importante para estabelecer um protocolo de acompanhamento oftalmológico, para prevenir um dano visual clinicamente grave, aumentando a qualidade de vida destes pacientes.

Clinical, hematological, and molecular characterization of sickle cell anemia pediatric patients from two different cities in Brazil

O objetivo desse estudo foi avaliar aspectos clínicos, hematológicos e moleculares de pacientes pediátricos portadores de anemia falciforme em duas cidades brasileiras: Salvador e São Paulo. Foram estudados 71 pacientes com idades variando entre 3 a 18 anos, analisando-se os seguintes aspectos: perfis hematológicos, haplótipos dos genes da globina b, presença de talassemia a-23.7kb, número de internações por vaso-oclusão, infecção, presença de acidente vascular cerebral e litíase biliar. O genótipo Ben/CAR predominou nas duas cidades. Talassemia a-23.7kb teve freqüência de 28,2 por cento em Salvador e 22,5 por cento em São Paulo. Os pacientes de São Paulo apresentaram um número maior de internações por vaso-oclusão nos diferentes genótipos. Esses dados sugeriram um fenótipo com menor gravidade clínica nos pacientes de Salvador, possivelmente relacionados a fatores genéticos, ambientais e sócio-econômicos. Estudos adicionais necessitam ser realizados com intuito de elucidar os efeitos moduladores na expressão gênica da doença.

Clinical, hematological, and molecular characterization of sickle cell anemia pediatric patients from two different cities in Brazil.

This study focused on clinical, hematological, and molecular aspects of sickle cell anemia pediatric patients from two different cites in Brazil. Seventy-one patients from São Paulo and Salvador, aged 3 to 18 years, were evaluated. Hematological analyses, betaS globin gene haplotypes, and alpha2 3.7kb-thalassemia were performed. Numbers of hospitalizations due to vaso-occlusive crises, infections, stroke, and cholelithiasis were investigated. São Paulo had more hospitalizations from vaso-occlusion, cholelithiasis, and stroke than Salvador. The Ben/CAR genotype predominated in both cities. Alpha2 3.7kb-thalassemia had a frequency of 28.2% in Salvador, mostly with Ben/CAR genotype (45.0%), while São Paulo had 22.5% with similar frequencies of the Ben/ CAR and CAR/CAR genotypes. Sickle cell anemia patients from São Paulo also had more episodes of stroke, which was observed among CAR/CAR, atypical, and BEN/CAR haplotypes. In Salvador stroke was only observed in the Ben/CAR genotype. Cholelithiasis had similar frequencies in the two cities. These data suggest a milder phenotype among patients in Salvador, possibly due to genetic, environmental, and socioeconomic factors. Further studies are needed to elucidate modulating factors and phenotype association.