TGFBR3 Polymorphisms (rs1805110 and rs7526590) Are Associated with Laboratory Biomarkers and Clinical Manifestations in Sickle Cell Anemia

Individuals with sickle cell anemia (SCA) present chronic anemia, hemolysis, an exacerbated inflammatory response, and heterogeneous clinical complications, which may be modulated by the transforming growth factor beta (TGF-β) pathway. Thus, we aimed to investigate polymorphisms (rs1805110 and rs7526590) of the transforming growth factor beta receptor III gene (TGFBR3) with regard to laboratory biomarkers and clinical manifestations in individuals with SCA. Hematological, biochemical, immunological, and genetic analyses were carried out, as well as serum endothelin-1 measurements. The minor allele (A) of the TGFBR3 rs1805110 polymorphism was associated with increased hemoglobin, hematocrit, reticulocyte counts, total cholesterol, low-density lipoprotein, uric acid, and endothelin levels, as well as decreased platelet distribution width (PDW) and the occurrence of bone alterations. The minor allele (T) of TGFBR3 rs7526590 was associated with increased red cell distribution width, PDW, alkaline phosphatase, aspartate aminotransferase, total and indirect bilirubin, and lactate dehydrogenase levels, as well as lower ferritin levels and the occurrence of leg ulcers. Our data suggest that the minor allele (A) of TGFBR3 rs1805110 is associated with inflammation and bone alterations, while the minor allele (T) of TGFBR3 rs7526590 is related to hemolysis and the occurrence of leg ulcers

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

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-03T15:47:25Z No. of bitstreams: 1 Santiago RP Laboratory and Genetic Biomarkers ....pdf: 1064827 bytes, checksum: f8adf15050f31e72f748e3bd19b819aa (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-03T16:19:03Z (GMT) No. of bitstreams: 1 Santiago RP Laboratory and Genetic Biomarkers ....pdf: 1064827 bytes, checksum: f8adf15050f31e72f748e3bd19b819aa (MD5)Made available in DSpace on 2018-04-03T16:19:03Z (GMT). No. of bitstreams: 1 Santiago RP Laboratory and Genetic Biomarkers ....pdf: 1064827 bytes, checksum: f8adf15050f31e72f748e3bd19b819aa (MD5) Previous issue date: 2017Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) (SUS0034/2013 and 8133/2014).Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Ambulatório Pediátrico de Doença Cerebrovascular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Hospital Universitário Professor Edgard Santos. Serviço de Pediatria. Salvador, BA, Brasil / Universidade Salvador. Laureate International Universities. Salvador, BA, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilReference 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

Leptin − 2548 G > A gene polymorphism is associated with lipids metabolism and TGF-β alteration in sickle cell disease

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-03-20T17:31:26Z No. of bitstreams: 1 Figueiredo CVB Leptin - 2548 G....pdf: 553428 bytes, checksum: e391c0811c0d246083cb39c47fcac391 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-03-20T17:41:54Z (GMT) No. of bitstreams: 1 Figueiredo CVB Leptin - 2548 G....pdf: 553428 bytes, checksum: e391c0811c0d246083cb39c47fcac391 (MD5)Made available in DSpace on 2017-03-20T17:41:54Z (GMT). No. of bitstreams: 1 Figueiredo CVB Leptin - 2548 G....pdf: 553428 bytes, checksum: e391c0811c0d246083cb39c47fcac391 (MD5) Previous issue date: 2016Brazilian National Council of Research (CNPq) (3065427/2007-5 and 484457/2007-1) (M.S.G.); the Foundation of Research and Extension of Bahia (FAPESB) (1431040053063 and 9073/2007) (M.S.G.); and MCD/CNPq/MS-SCTIE-DECIT (409800/2006-6), (M.S.G.).Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilComplexo Hospitalar Universitário Professor Edgard Santos. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação de Hematologia e Hemoterapia da Bahia (HEMOBA). Salvador, BA, BrasilComplexo Hospitalar Universitário Professor Edgard Santos. Salvador, BA, Brasil / Fundação de Hematologia e Hemoterapia da Bahia (HEMOBA). Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilBackground: Leptin is a proteinwith regulatory role in several body systems such as the immune system, and energy balance. Given that patients with sickle cell disease (SCD) have changes in cellular immunity and lipid metabolism, it is important to conduct research aimed understand the role of leptin in the pathophysiology of SCD. Results:We studied 103 patients with SCD from Northeast of Brazil in a case-control study. The investigation of the leptin −2548 G N A polymorphism in SCD individuals shows the frequency of 60.20% (62/103) for the wild genotype (GG); 34.95% (36/103) for the heterozygous genotype (AG) and 4.85% (5/103) for the variant homozygote genotype (AA). In the healthy volunteers group the polymorphism investigation indicated the frequency of 58.24% (53/91) for the wild genotype (GG); 37.36% (34/91) for the heterozygous genotype (AG) and 4.40% (4/ 91) for the variant homozygote genotype (AA). The AA genotype was associated with increased levels of verylow- density lipoprotein cholesterol (VLDL-C) and triglycerides among SCD patients. Furthermore, the presence of allele A was associated with the highest levels of transforming growth factor beta (TGF-β) in SCD patients. Conclusion: The results suggest that the presence of the variant allele may influence the disturbances in lipidmetabolism and serum levels of TGF-β described in SCD patients

Association of classical markers and establishment of the dyslipidemic sub-phenotype of sickle cell anemia

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-02-27T12:18:31Z No. of bitstreams: 1 Aleluia MM Association of classical markers .....pdf: 860152 bytes, checksum: 3d350917bf35d954035fab3e69fc707f (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-02-27T12:31:07Z (GMT) No. of bitstreams: 1 Aleluia MM Association of classical markers .....pdf: 860152 bytes, checksum: 3d350917bf35d954035fab3e69fc707f (MD5)Made available in DSpace on 2018-02-27T12:31:07Z (GMT). No. of bitstreams: 1 Aleluia MM Association of classical markers .....pdf: 860152 bytes, checksum: 3d350917bf35d954035fab3e69fc707f (MD5) Previous issue date: 2017Gonçalo Moniz Institute at the Oswaldo Cruz Foundation (IGM-FIOCRUZ – Bahia - Brazil) (CAAE 08452913.9.0000.0040).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia e Genética Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia e Genética Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia e Genética Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Centro de Referência a Doença Falciforme de Itabuna. Itabuna, BA, Brasil / Universidade Estadual de Santa Cruz. Ilhéus, BA, Brasil.Centro de Referência a Doença Falciforme de Itabuna. Itabuna, BA, Brasil.Centro de Referência a Doença Falciforme de Itabuna. Itabuna, BA, Brasil / Universidade Estadual de Santa Cruz. Ilhéus, BA, Brasil.Universidade Estadual de Santa Cruz. Ilhéus, BA, Brasil.Universidade Estadual de Santa Cruz. Ilhéus, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia e Genética Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia e Genética Computacional. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia e Genética Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Universidade Federal da Bahia. Salvador, BA, Brasil.Universidade Estadual da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Hematologia e Genética Computacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Sickle cell anemia (SCA) patients exhibit sub-phenotypes associated to hemolysis and vaso-occlusion. The disease has a chronic inflammatory nature that has been also associated to alterations in the lipid profile. This study aims to analyze hematological and biochemical parameters to provide knowledge about the SCA sub-phenotypes previously described and suggest a dyslipidemic sub-phenotype. Methods: A cross-sectional study was conducted from 2013 to 2014, and 99 SCA patients in steady state were enrolled. We assessed correlations and associations with hematological and biochemical data and investigated the co-inheritance of -α3.7Kb-thalassemia (-α3.7Kb-thal). Correlation analyses were performed using Spearman and Pearson coefficient. The median of quantitative variables between two groups was compared using t-test and Mann-Whitney. P-values <0.05 were considered statistically significant. Results: We found significant association of high lactate dehydrogenase levels with decreased red blood cell count and hematocrit as well as high levels of total and indirect bilirubin. SCA patients with low nitric oxide metabolites had high total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol and reduced very low-density cholesterol, triglycerides, direct bilirubin level and reticulocyte counts. In SCA patients with high-density lipoprotein cholesterol greater than 40 mg/dL, we observed increased red blood cell count, hemoglobin, hematocrit, and fetal hemoglobin and decreased nitric oxide metabolites levels. The presence of -α3.7Kb-thal was associated with high red blood cell count and low mean corpuscular volume, mean corpuscular hemoglobin, platelet count and total and indirect bilirubin levels. Conclusions: Our results provide additional information about the association between biomarkers and co-inheritance of -α3.7Kb-thal in SCA, and suggest the role of dyslipidemia and nitric oxide metabolites in the characterization of this sub-phenotype

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

A Description of the Hemolytic Component in Sickle Leg Ulcer: The Role of Circulating miR-199a-5p, miR-144, and miR-126

Sickle leg ulcers (SLU) are malleoli lesions with exuberant hemolytic pathophysiology. The microRNAs are potential genetic biomarkers for several pathologies. Thereby, we aimed to assess the expression of circulating miR-199a-5p, miR-144, and miR-126 in association with hemolytic biomarkers in SLU. This cross-sectional study included 69 patients with sickle cell disease, 52 patients without SLU (SLU-) and 17 patients with active SLU or previous history (SLU+). The results demonstrated elevated expression of circulating miR-199a-5p and miR-144 in SLU+ patients while miR-126 expression was reduced. Circulating miR-199a-5p and miR-144 were associated with hemolytic biomarkers such as LDH, indirect bilirubin, AST, GGT, iron, ferritin, RBC, hemoglobin, and NOm, in addition to association with impaired clinical profile of SLU. Furthermore, in silico analyses indicated interactions of miR-199a-5p with HIF1A, Ets-1, and TGFB2 genes, which are associated with vasculopathy and reduced NO. In contrast, miR-126 was associated with an attenuating clinical profile of SLU, in addition to not characterizing hemolysis. In summary, this study demonstrates, for the first time, that hemolytic mechanism in SLU can be characterized by circulating miR-199a-5p and miR-144. The circulating miR-126 may play a protective role in SLU. Thus, these microRNAs can support to establish prognosis and therapeutic strategy in SLU

Genetic Polymorphisms Associated with Environmental Exposure to Polycyclic Derivatives in African Children

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-09-27T12:54:12Z No. of bitstreams: 1 Oliveira RM Genetic Polymorphisms Associated .....pdf: 1817455 bytes, checksum: 0b4f5adc5ac0494c103edf631918739c (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-09-27T13:38:49Z (GMT) No. of bitstreams: 1 Oliveira RM Genetic Polymorphisms Associated .....pdf: 1817455 bytes, checksum: 0b4f5adc5ac0494c103edf631918739c (MD5)Made available in DSpace on 2018-09-27T13:38:49Z (GMT). No. of bitstreams: 1 Oliveira RM Genetic Polymorphisms Associated .....pdf: 1817455 bytes, checksum: 0b4f5adc5ac0494c103edf631918739c (MD5) Previous issue date: 2018Fundação de Amparo à Pesquisa do Estado da Bahia under Grant no. PET0018/2010.Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, BrasilThe nonracial leukopenia may be a result of exposure to polycyclic derivatives (benzene-toluene-xylene (BTX)) and may arise from a possible change in the bone marrow microenvironment. The present study sought to evaluate the association of genetic polymorphisms in xenobiotic-metabolizing enzymes with hematological and biochemical profiles. Methods. We evaluated 89 African descendant children, exposed indirectly to benzene derivatives. Laboratory parameters were investigated by automated methods and genetic polymorphisms by PCR-RFLP and PCR multiplex. Results. Children with leukopenia had significantly decreased white blood cells (WBCs) and platelet counts, which is not consistent with benign leukopenia. In the same group, we have found that carriers of the CYP2E1 variant allele had decreased WBC and lymphocytes. Those with NQO1 variant allele had decreased WBC, neutrophil, eosinophil, monocyte, and lymphocyte counts. Carriers of the MPO variant allele had decreased WBC, neutrophil, eosinophil, basophil, monocyte, lymphocyte, and platelet counts and an elevated free iron level. Children with GSTT and GSTM null exhibited decreased WBC, neutrophil, basophil, and lymphocyte counts. Our multivariate analysis model reveals that females were independently associated with leukopenia. Conclusion. Our results suggest that the polymorphisms investigated were associated with hematological changes in the studied population. These alterations could be heightened by exposure to benzene derivatives

Sickle cell disease: A distinction of two most frequent genotypes (HbSS and HbSC).

Sickle cell disease (SCD) consists of a group of hemoglobinopathies in which individuals present highly variable clinical manifestations. Sickle cell anemia (SCA) is the most severe form, while SC hemoglobinopathy (HbSC) is thought to be milder. Thus, we investigated the clinical manifestations and laboratory parameters by comparing each SCD genotype. We designed a cross-sectional study including 126 SCA individuals and 55 HbSC individuals in steady-state. Hematological, biochemical and inflammatory characterization was performed as well as investigation of previous history of clinical events. SCA patients exhibited most prominent anemia, hemolysis, leukocytosis and inflammation, whereas HbSC patients had increased lipid determinations. The main cause of hospitalization was pain crises on both genotypes. Vaso-occlusive events and pain crises were associated with hematological, inflammatory and anemia biomarkers on both groups. Cluster analysis reveals hematological, inflammatory, hemolytic, endothelial dysfunction and anemia biomarkers in HbSC disease as well as SCA. The results found herein corroborate with previous studies suggesting that SCA and HbSC, although may be similar from the genetic point of view, exhibit different clinical manifestations and laboratory alterations which are useful to monitor the clinical course of each genotype

Serum haptoglobin and hemopexin levels are depleted in pediatric sickle cell disease patients

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-09-27T12:08:03Z No. of bitstreams: 1 Santiago RP Serum haptoglobin and hemopexin....pdf: 558545 bytes, checksum: 573c37ecedf17c3ca8fb53b59dabb35a (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-09-27T12:26:56Z (GMT) No. of bitstreams: 1 Santiago RP Serum haptoglobin and hemopexin....pdf: 558545 bytes, checksum: 573c37ecedf17c3ca8fb53b59dabb35a (MD5)Made available in DSpace on 2018-09-27T12:26:56Z (GMT). No. of bitstreams: 1 Santiago RP Serum haptoglobin and hemopexin....pdf: 558545 bytes, checksum: 573c37ecedf17c3ca8fb53b59dabb35a (MD5) Previous issue date: 2018FAPESB SUS0034/2013 and 8133/2014 and by NIH R01 HL114567.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFundação de Hematologia e Hemoterapia da Bahia. Salvador, BA, Brasil / Universidade Salvador. Laureate University. Salvador, BA, BrasilFundação de Hematologia e Hemoterapia da Bahia. Salvador, BA, BrasilUniversity of Minnesota. Department of Medicine. Division of Hematology, Oncology and Transplantation. Minneapolis, MN, USAUniversity of Minnesota. Department of Medicine. Division of Hematology, Oncology and Transplantation. Minneapolis, MN, USAFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasi

Hydroxyurea alters hematological, biochemical and inflammatory biomarkers in Brazilian children with SCA: Investigating associations with βS 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 βS 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 βS haplotypes or α-thalassemia, HU seems to be linked to alterations in hemolytic, inflammatory, hepatic, lipid and glycemic profiles