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3.
Malar J ; 18(1): 14, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30665411

RESUMO

BACKGROUND: Glucose-6-phosphate dehydrogenase deficiency (G6PDd), haemoglobin C (HbC) and S (HbS) are inherited blood disorders (IBD) common in populations in malaria endemic areas. All are associated to some degree with protection against clinical malaria whilst additionally G6PDd is associated with haemolysis following treatment with 8-aminoquinolines. Measuring the prevalence of these inherited blood disorders in affected populations can improve understanding of disease epidemiology. Current methodologies in epidemiological studies commonly rely on individual target amplification and visualization; here a method is presented to simultaneously detect the polymorphisms and that can be expanded to include other single nucleotide polymorphisms (SNPs) of interest. METHODS: Human DNA from whole blood samples was amplified in a novel, multiplex PCR reaction and extended with SNP-specific probes in an allele specific primer extension (ASPE) to simultaneously detect four epidemiologically important human markers including G6PD SNPs (G202A and A376G) and common haemoglobin mutations (HbS and HbC). The products were hybridized to magnetic beads and the median fluorescence intensity (MFI) was read on MAGPIX® (Luminex corp.). Genotyping data was compared to phenotypical data generated by flow cytometry and to established genotyping methods. RESULTS: Seventy-five samples from Burkina Faso (n = 75/78, 96.2%) and 58 samples from The Gambia (n = 58/61, 95.1%) had a G6PD and a HBB genotype successfully assigned by the bead-based assay. Flow cytometry data available for n = 61 samples further supported the concordance between % G6PD normal/deficient cells and genotype. CONCLUSIONS: The bead based assay compares well to alternative measures of genotyping and phenotyping for G6PD. The screening is high throughput, adaptable to inclusion of multiple targets of interest and easily standardized.


Assuntos
Anemia Falciforme/diagnóstico , Técnicas de Genotipagem/métodos , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Doença da Hemoglobina C/diagnóstico , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Burkina Faso , Criança , Glucosefosfato Desidrogenase/genética , Hemoglobina C/genética , Hemoglobina Falciforme/genética , Humanos , Malária/complicações , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Am J Hematol ; 94(1): 39-45, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30290004

RESUMO

Sickle cell disease (SCD) is a common, life-threatening genetic disorder that is best managed when diagnosed early by newborn screening. However, SCD is most prevalent in low-resource regions of the world where newborn screening is rare and diagnosis at the point-of-care is challenging. In many such regions, the majority of affected children die, undiagnosed, before the age of 5 years. A rapid and affordable point-of-care test for SCD is needed. The diagnostic accuracy of HemoTypeSC, a point-of-care immunoassay, for SCD was evaluated in individuals who had SCD, hemoglobin C disease, the related carrier (trait) states, or a normal hemoglobin phenotype. Children and adults participated in low-, medium- and high-resource environments (Ghana [n = 383], Martinique [n = 46], and USA [n = 158]). Paired blood specimens were obtained for HemoTypeSC and a reference diagnostic assay. HemoTypeSC testing was performed at the site of blood collection, and the reference test was performed in a laboratory at each site. In 587 participants, across all study sites, HemoTypeSC had an overall sensitivity of 99.5% and specificity of 99.9% across all hemoglobin phenotypes. The test had 100% sensitivity and specificity for sickle cell anemia. Sensitivity and specificity for detection of normal and trait states were >99%. HemoTypeSC is an inexpensive (<$2 per test), accurate, and rapid point-of-care test that can be used in resource-limited regions with a high prevalence of SCD to provide timely diagnosis and support newborn screening programs.


Assuntos
Anemia Falciforme/diagnóstico , Imunoensaio , Sistemas Automatizados de Assistência Junto ao Leito , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/epidemiologia , Anticorpos Monoclonais/imunologia , Criança , Países em Desenvolvimento , Diagnóstico Precoce , Feminino , Gana/epidemiologia , Hemoglobina A/análise , Hemoglobina C/análise , Doença da Hemoglobina C/sangue , Doença da Hemoglobina C/diagnóstico , Doença da Hemoglobina C/epidemiologia , Hemoglobina Falciforme/análise , Humanos , Imunoensaio/economia , Recém-Nascido , Masculino , Martinica/epidemiologia , Triagem Neonatal/economia , Triagem Neonatal/métodos , Prevalência , Estudos Prospectivos , Sensibilidade e Especificidade , Traço Falciforme/sangue , Traço Falciforme/diagnóstico , Traço Falciforme/epidemiologia , Método Simples-Cego
6.
Pediatr Blood Cancer ; 64(8)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28121068

RESUMO

A 17-year-old male presented with acute hemolysis with stomatocytosis, elevated mean corpuscular hemoglobin concentration (MCHC), and osmotic gradient ektacytometry consistent with marked erythrocyte dehydration. Erythrocytes from both parents also demonstrated evidence of dehydration with elevated MCHC and abnormal ektacytometry, but neither to the degree of the patient. Genetic studies revealed the patient had hereditary xerocytosis (HX) due to a novel PIEZO1 mutation inherited from his mother and hemoglobin C (HbC) trait inherited from his father. HbC trait accentuated the erythrocyte dehydration of HX. Coinheritance of interrelated disorders and/or modifier alleles should be considered whenever severe erythrocyte dehydration is observed.


Assuntos
Anemia Hemolítica Congênita/complicações , Anemia Hemolítica Congênita/genética , Eritrócitos/patologia , Doença da Hemoglobina C/complicações , Doença da Hemoglobina C/genética , Hidropisia Fetal/genética , Adolescente , Anemia Hemolítica Congênita/sangue , Índices de Eritrócitos , Doença da Hemoglobina C/sangue , Humanos , Hidropisia Fetal/sangue , Canais Iônicos/genética , Masculino , Mutação
7.
Tunis Med ; 95(12): 229-233, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29878289

RESUMO

BACKGROUND: - Hemoglobin C is a hemoglobin variant encountered worldwide. The regionswith high prevalence are West Africa and South-East Asia.The objective of this study is to report cases of hemoglobin C disease brought together during these last twelve years in the Laboratory of Biochemistry and Toxicology of RabatMilitary Hospital Mohammed V (MHIMV). METHODS: - This was a retrospective study including111 cases of hemoglobin C disease collected in the Laboratory of Biochemistry of the MHIMVover the past 12 years. A questionnairewasfulfilledwith the epidemiological data,clinical data and the results of the biological explorations. The screening of the hemoglobin variant in this study included several biochemical (hemoglobin electrophoresis at acid and alkalinepH) and hematological tests. RESULTS: - Sex-ratio was equal to 1,22. The age at the time of diagnosis ranges between 4 and 80years old, with the mean of 38. North-West regions of Morocco seem most affected. The most frequent reasons for prescription of the hemoglobin's studywere: biological abnormalities, splenomegaly and anemic syndrome. Blood smear reveals frequently anisopoikilocytosis and red blood target. The biochemical tests contribute to the diagnosis and reveal various and varied etiological groups: heterozygous A/C (75%),homozygous C/C (8%), double heterozygous S/C (9%),C/ß+-thal (6%) andC/O-Arab (2%). Conclusion - The results of the present descriptive study are in line with the literature data. The importance of genetic counseling and the installation of a national card of systematic neonatal tracking seemto be unavoidable.


Assuntos
Doença da Hemoglobina C/diagnóstico , Doença da Hemoglobina C/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletroforese das Proteínas Sanguíneas , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Testes Genéticos , Testes Hematológicos , Hemoglobina C/análise , Hemoglobina C/genética , Hemoglobina C/metabolismo , Doença da Hemoglobina C/sangue , Doença da Hemoglobina C/genética , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos/epidemiologia , Estudos Retrospectivos , Adulto Jovem
8.
Clin Hemorheol Microcirc ; 61(4): 571-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25335812

RESUMO

Patients with hemoglobin C disease (CC) usually do not develop severe complications in comparison with individuals with sickle cell anemia (SS) or with sickle cell hemoglobin C disease (SC). The present study compared the hematological, biochemical, hemorheological and clinical characteristics of CC patients to those of SS, SC and healthy individuals (AA). Blood viscosity was measured at 225 s(-1) with a cone plate viscometer. The hematocrit-to-blood viscosity ratio (HVR), i.e. an index of red blood cell (RBC) oxygen transport effectiveness, was calculated. RBC deformability was determined at 30 Pa by ektacytometry, and RBC aggregation properties by syllectometry. CC and SC had higher blood viscosity and lower HVR than AA. Nevertheless, HVR was higher in CC compared to SS and tended to be higher than in SC. The CC group exhibited very rigid hyperchromic RBC compared to the three other groups. RBC aggregation abnormalities were observed in CC: low RBC aggregation index and high RBC aggregates strength. Despite these hemorheological abnormalities, CC never had hospitalized painful vaso-occlusive crisis or acute chest syndrome. In contrast, all of them had splenomegaly. Of note, 2 out of 7 CC developed retinopathy or otologic disorders. Whether the blood hyperviscosity and decreased RBC deformability are responsible for these complications is unknown. The higher oxygen transport effectiveness (i.e., HVR) of CC compared to SS is probably at the origin of the very low risk of medical complication in this population.


Assuntos
Eritrócitos/metabolismo , Doença da Hemoglobina C/sangue , Hemorreologia , Adulto , Viscosidade Sanguínea , Contagem de Eritrócitos , Deformação Eritrocítica , Feminino , Doença da Hemoglobina C/patologia , Humanos , Masculino , Pessoa de Meia-Idade
9.
J Am Soc Nephrol ; 27(5): 1300-4, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26546258

RESUMO

Sickle cell nephropathy is a common complication in patients with sickle cell hemoglobinopathies. In these disorders, polymerization of mutated hemoglobin S results in deformation of red blood cells, which can cause endothelial cell injury in the kidney that may lead to thrombus formation when severe or manifest by multilayering of the basement membranes (glomerular and/or peritubular capillaries) in milder forms of injury. As the injury progresses, the subsequent ischemia, tubular dysfunction, and glomerular scarring can result in CKD or ESRD. Sickle cell nephropathy can occur in patients with homozygous hemoglobin SS or heterozygous hemoglobin S (hemoglobin SC, hemoglobin S/ß(0)-thalassemia, and hemoglobin S/ß(+)-thalassemia). Clinical manifestations resulting from hemoglobin S polymerization are often milder in patients with heterozygous hemoglobin S. These patients may not present with clinically apparent acute sickle cell crises, but these milder forms can provide a unique view of the kidney injury in sickle cell disease. Here, we report a patient with hemoglobin SC disease who showed peritubular capillary and vasa recta thrombi and capillary basement membrane alterations primarily involving the renal medulla. This patient highlights the vascular occlusion and endothelial cell injury in the medulla that contribute to sickle cell nephropathy.


Assuntos
Anemia Falciforme/complicações , Doença da Hemoglobina C/complicações , Nefropatias/etiologia , Medula Renal/irrigação sanguínea , Trombose/etiologia , Adulto , Biópsia , Feminino , Humanos , Medula Renal/patologia , Microvasos , Traço Falciforme , Trombose/patologia
10.
Transfusion ; 56(1): 119-24, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26337929

RESUMO

BACKGROUND: Pregnancy represents a challenge for women with sickle cell disease (SCD), with higher rates of both maternal and fetal complications. The aim of this study was to evaluate the impact of prophylactic transfusion support administered specifically to pregnant women with sickle hemoglobin C disease. MATERIALS AND METHODS: Patients were divided into two groups according to the type of transfusion support received: 10 women received prophylactic erythrocytapheresis or manual exchange transfusion at 28 weeks of gestation, and 14 received transfusions only on demand, due to acute complications, or received no transfusions at all. RESULTS: Our results indicated higher frequencies of SCD-related complications in the group that did not receive prophylactic transfusion support (35.7% vs. only 10% in the erythrocytapheresis group). Furthermore, these complications were more severe in this group and included all cases of acute chest syndrome. A significant difference was observed concerning gestational age at birth (38.7 weeks in the transfusion group vs. 34.4 weeks, p = 0.037), with a higher frequency of preterm births in the nontransfused group (69.23% vs. 30% in the transfusion group). CONCLUSION: We demonstrated a clear reduction of unfavorable outcomes in patients receiving prophylactic transfusions, probably reflecting better maternal and fetal conditions, which corroborated to the more satisfactory indices of vitality, observed in newborns. Considering that erythrocytapheresis or manual exchange transfusions both represent feasible and safe procedures, they could represent important tools for the optimal management of these patients.


Assuntos
Remoção de Componentes Sanguíneos , Transfusão de Eritrócitos , Transfusão Total , Doença da Hemoglobina C/terapia , Complicações Hematológicas na Gravidez/terapia , Cuidado Pré-Natal/métodos , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações na Gravidez/prevenção & controle , Resultado do Tratamento
12.
Hemoglobin ; 38(5): 316-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25271992

RESUMO

The aim of this study was the determination of hemoglobin (Hb) variants and ABO blood groups in a school population aged 6 to 9 years in the township of Agbandé-Yaka in North Togo. A cross-sectional study was carried out on 570 children of four primary schools at Agbande-Yaka, between March and July 2010. Hemoglobin characterization was done by alkaline buffer electrophoresis and the blood types ABO-Rhesus (Rh) D by immuno-hematological methods. A Hb variant was detected in 37.0% of the schoolchildren. Among them, the AS trait accounted for 11.9% and the AC trait for 20.2%. Homozygous Hb S (HBB: c.20A>T) was not found but Hb C (HBB: c.19G>A) appeared at a frequency of 3.3%, while compound heterozygotes carrying Hb SC were seen at a frequency of 1.6%. The O, B and A blood groups accounted for 49.0, 26.8 and 21.9%, respectively. The Hb anomalies reached a high prevalence in this school population. These results are remarkable by the absence of homozygous Hb S individuals compared to homozygous Hb C individuals, which were as numerous as expected. The frequencies of the ABO blood groups are similar to what has been found in other West African populations.


Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Doença da Hemoglobina C/epidemiologia , Hemoglobina C/análise , Doença da Hemoglobina SC/epidemiologia , Hemoglobina Falciforme/análise , Polimorfismo de Nucleotídeo Único , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Alelos , Criança , Estudos Transversais , Feminino , Frequência do Gene , Hemoglobina C/genética , Doença da Hemoglobina C/sangue , Doença da Hemoglobina C/genética , Doença da Hemoglobina SC/sangue , Doença da Hemoglobina SC/genética , Hemoglobina Falciforme/genética , Heterozigoto , Homozigoto , Humanos , Masculino , Programas de Rastreamento , Prevalência , Instituições Acadêmicas , Togo/epidemiologia
14.
Clin Hemorheol Microcirc ; 58(2): 307-16, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23302597

RESUMO

Vascular function has been found to be impaired in patients with sickle cell disease (SCD). The present study investigated the determinants of systemic vascular resistance in two main SCD syndromes in children: sickle cell anemia (SCA) and sickle cell-hemoglobin C disease (SCC). Nitric oxide metabolites (NOx), hematological, hemorheological, and hemodynamical parameters were investigated in 61 children with SCA and 49 children with SCC. While mean arterial pressure was not different between SCA and SCC children, systemic vascular resistance (SVR) was greater in SCC children. Although SVR and blood viscosity (ηb) were not correlated in SCC children, the increase of ηb (+18%) in SCC children compared to SCA children results in a greater mean SVR in this former group. SVR was positively correlated with ηb, hemoglobin (Hb) level and RBC deformability, and negatively with NOx level in SCA children. Multivariate linear regression model showed that both NOx and Hb levels were independently associated with SVR in SCA children. In SCC children, only NOx level was associated with SVR. In conclusion, vascular function of SCC children seems to better cope with higher ηb compared to SCA children. Since the occurrence of vaso-occlusive like complications are less frequent in SCC than in SCA children, this finding suggests a pathophysiological link between the vascular function alteration and these clinical manifestations. In addition, our results suggested that nitric oxide metabolism plays a key role in the regulation of SVR, both in SCA and SCC.


Assuntos
Anemia Falciforme/sangue , Doença da Hemoglobina C/sangue , Óxido Nítrico/metabolismo , Viscosidade Sanguínea , Criança , Feminino , Humanos , Masculino , Reologia , Resistência Vascular
15.
Blood ; 122(22): 3698, 2013 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-24263962
17.
Am J Hematol ; 88(8): 661-4, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23657867

RESUMO

The known biophysical variations of hemoglobin (Hb) S and Hb C may result in hemodynamic differences between subjects with SS and SC disease. The purpose of this study was to measure and compare conjunctival hemodynamics between subjects with Hb SS and SC hemoglobinopathies. Image sequences of the conjunctival microcirculation were acquired in 9 healthy control subjects (Hb AA), 24 subjects with SC disease, and 18 subjects with SS disease, using a prototype imaging system. Diameter (D) and blood velocity (V) measurements were obtained in multiple venules of each subject. Data were categorized according to venule caliber by averaging V and D for venules with diameters less than (vessel size 1) or greater than (vessel size 2) 15 µm. V in vessel size 2 was significantly greater than V in vessel size 1 in the AA and SS groups (P ≥ 0.009), but not in the SC group (P = 0.1). V was significantly lower in the SC group as compared to the SS group (P = 0.03). In AA and SS groups, V correlated with D (P ≤ 0.005), but the correlation was not statistically significant in the SC group (P = 0.08). V was inversely correlated with hematocrit in the SS group for large vessels (P = 0.03); however, no significant correlation was found in the SC group (P ≥ 0.2). Quantitative assessment of conjunctival microvascular hemodynamics in SS and SC disease may advance understanding of sickle cell disease pathophysiology and thereby improve therapeutic interventions.


Assuntos
Anemia Falciforme/fisiopatologia , Túnica Conjuntiva/irrigação sanguínea , Túnica Conjuntiva/fisiopatologia , Doença da Hemoglobina C/fisiopatologia , Adulto , Anemia Falciforme/genética , Anemia Falciforme/patologia , Velocidade do Fluxo Sanguíneo , Feminino , Hematócrito , Doença da Hemoglobina C/genética , Doença da Hemoglobina C/patologia , Hemoglobina Falciforme/genética , Humanos , Masculino , Pessoa de Meia-Idade , Vênulas/fisiopatologia
18.
Sci Rep ; 3: 1671, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23591685

RESUMO

Haemoglobin C (HbC) is one of the commonest structural haemoglobin variants in human populations. Although HbC causes mild clinical complications, its diagnosis and genetic counselling are important to prevent inheritance with other haemoglobinopathies. Little is known about its contemporary distribution and the number of newborns affected. We assembled a global database of population surveys. We then used a Bayesian geostatistical model to create maps of HbC frequency across Africa and paired our predictions with high-resolution demographics to calculate heterozygous (AC) and homozygous (CC) newborn estimates and their associated uncertainty. Data were too sparse outside Africa for this methodology to be applied. The highest frequencies were found in West Africa but HbC was commonly found in other parts of the continent. The expected annual numbers of AC and CC newborns in Africa were 672,117 (interquartile range (IQR): 642,116-705,163) and 28,703 (IQR: 26,027-31,958), respectively. These numbers are about two times previous estimates.


Assuntos
Doença da Hemoglobina C/sangue , Doença da Hemoglobina C/epidemiologia , Hemoglobina C/análise , Modelos de Riscos Proporcionais , África/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Prevalência , Fatores de Risco
19.
Clin Hemorheol Microcirc ; 55(2): 205-12, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23076002

RESUMO

Little is known about the impact of blood rheology on the occurrence of retinopathy in sickle cell disease (SCD). Fifty-nine adult SCD patients in steady-state condition participated to the study: 32 with homozygous SCD (sickle cell anemia; SCA) and 27 with sickle cell hemoglobin-C disease (SCC). The patients underwent retinal examination and were categorized according to the classification of Goldberg: 1) no retinopathy (group 1), 2) non-proliferative or proliferative stage I-II retinopathy (group 2) and 3) proliferative stage III-IV-V retinopathy (group 3). Hematological and hemorheological (whole blood viscosity, RBC deformability and aggregation properties) measurements were performed for each patient. In the whole SCD group (SCA + SCC patients) and in SCC patients, the group 3 had higher platelets count than group 2 but the difference between group 3 and group 1 did not reach statistical significance. No difference was observed for the other parameters between the three groups. SCC patients from the group 3 exhibited higher whole blood viscosity than SCC patients from the group 1. No significant difference was observed between the three groups in SCA patients. This study revealed that severe sickle proliferative retinopathy is associated with blood hyperviscosity in SCC patients but not in SCA patients.


Assuntos
Anemia Falciforme/complicações , Doença da Hemoglobina C/complicações , Doenças Retinianas/sangue , Adulto , Anemia Falciforme/sangue , Viscosidade Sanguínea , Feminino , Doença da Hemoglobina C/sangue , Humanos , Masculino , Doenças Retinianas/diagnóstico , Reologia/métodos , Adulto Jovem
20.
Br J Haematol ; 158(6): 788-97, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22775554

RESUMO

Chronic vascular inflammation and endothelial activation may initiate vaso-occlusion in sickle cell disease (SCD). TNFSF14 (CD258; LIGHT), a recently-identified pro-thrombotic and pro-inflammatory tumour necrosis factor (TNF)-superfamily cytokine, has a potent activating effect on endothelial cells. We evaluated whether TNFSF14 production is altered in SCD and whether platelets contribute to this production. TNFSF14 was measured in platelet-free plasma from healthy-control individuals (CON), steady-state sickle cell anaemia (SCA), SCA on hydroxycarbamide therapy (SCAHC) and haemoglobin SC (HbSC) patients. Mean plasma TNFSF14 was significantly increased in SCA, SCAHC and HbSC, compared to CON individuals. In SCA/SCAHC patients, plasma TNFSF14, showed no correlation with haematological variables, but was significantly correlated with serum lactate dehydrogenase and inflammatory markers (CD40LG , IL8 and ICAM1). Platelet-membrane TNFSF14 expression was significantly augmented on SCA platelets, and correlated with platelet activation; furthermore, measurement of platelet TNFSF14 release indicated that platelets may be a major source of circulating TNFSF14 in SCA. Interestingly, high plasma TNFSF14 was significantly associated with elevated tricuspid regurgitant velocity (≥2·5 m/s) in a population of SCA/SCAHC patients. The pro-inflammatory and atherogenic cytokine, TNFSF14, could contribute to endothelial activation and inflammation in SCA; future investigations may confirm whether this protein contributes to major clinical complications of the disease, such as pulmonary hypertension, and represents a potential therapeutic target.


Assuntos
Anemia Falciforme/sangue , Plaquetas/metabolismo , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/genética , Anemia Falciforme/patologia , Biomarcadores , Endotélio Vascular/patologia , Feminino , Genótipo , Hemoglobina C/genética , Doença da Hemoglobina C/sangue , Doença da Hemoglobina C/genética , Humanos , Hidroxiureia/uso terapêutico , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária , Membro 14 de Receptores do Fator de Necrose Tumoral/sangue , Traço Falciforme/sangue , Traço Falciforme/genética , Trombofilia/etiologia , Trombofilia/metabolismo , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/fisiologia , Adulto Jovem
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