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

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          Abstract

          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.

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          Most cited references29

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          Sickle-cell disease.

          With the global scope of sickle-cell disease, knowledge of the countless clinical presentations and treatment of this disorder need to be familiar to generalists, haematologists, internists, and paediatricians alike. Additionally, an underlying grasp of sickle-cell pathophysiology, which has rapidly accrued new knowledge in areas related to erythrocyte and extra-erythrocyte events, is crucial to an understanding of the complexity of this molecular disease with protean manifestations. We highlight studies from past decades related to such translational research as the use of hydroxyurea in treatment, as well as the therapeutic promise of red-cell ion-channel blockers, and antiadhesion and anti-inflammatory therapy. The novel role of nitric oxide in sickle-cell pathophysiology and the range of its potential use in treatment are also reviewed. Understanding of disease as the result of a continuing interaction between basic scientists and clinical researchers is best exemplified by this entity.
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            Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes.

            Hemolysis, long discounted as a critical measure of sickle cell disease severity when compared with sickle vaso-occlusion, may be the proximate cause of some disease complications. New mechanistic information about hemolysis and its effects on nitric oxide (NO) biology and further examination of the subphenotypes of disease requires a reappraisal and deconstruction of the clinical features of sickle cell disease. The biology underlying clinical phenotypes linked to hemolysis may increase our understanding of the pathogenesis of other chronic hemolytic diseases while providing new insights into treating sickle cell disease. The pathophysiological roles of dysregulated NO homeostasis and sickle reticulocyte adherence have linked hemolysis and hemolytic rate to sickle vasculopathy. Nitric oxide binds soluble guanylate cyclase which converts GTP to cGMP, relaxing vascular smooth muscle and causing vasodilatation. When plasma hemoglobin liberated from intravascularly hemolyzed sickle erythrocytes consumes NO, the normal balance of vasoconstriction:vasodilation is skewed toward vasoconstriction. Pulmonary hypertension, priapism, leg ulceration and stroke, all subphenotypes of sickle cell disease, can be linked to the intensity of hemolysis. Hemolysis plays less of a role in the vaso-occlusive-viscosity complications of disease like the acute painful episode, osteonecrosis of bone and the acute chest syndrome. Agents that decrease hemolysis or restore NO bioavailability or responsiveness may have potential to reduce the incidence and severity of the hemolytic subphenotypes of sickle cell disease. Some of these drugs are now being studied in clinical trials.
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              Single-tube multiplex-PCR screen for common deletional determinants of alpha-thalassemia.

              Alpha-thalassemia is very common throughout all tropical and subtropical regions of the world. In Southeast Asia and the Mediterranean regions, compound heterozygotes and homozygotes may have anemia that is mild to severe (hemoglobin [Hb] H disease) or lethal (Hb Bart's hydrops fetalis). We have developed a reliable, single-tube multiplex-polymerase chain reaction (PCR) assay for the 6 most frequently observed determinants of alpha-thalassemia. The assay allows simple, high throughput genetic screening for these common hematological disorders. (Blood. 2000;95:360-362)
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: InvestigationRole: Methodology
                Role: InvestigationRole: Methodology
                Role: InvestigationRole: MethodologyRole: Supervision
                Role: Formal analysisRole: InvestigationRole: Methodology
                Role: InvestigationRole: Methodology
                Role: InvestigationRole: MethodologyRole: Project administration
                Role: InvestigationRole: MethodologyRole: Project administration
                Role: InvestigationRole: Methodology
                Role: InvestigationRole: Methodology
                Role: Project administrationRole: Resources
                Role: Project administrationRole: Resources
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: Project administrationRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                29 January 2020
                2020
                : 15
                : 1
                : e0228399
                Affiliations
                [1 ] Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, FIOCRUZ-BA, Salvador, Bahia, Brasil
                [2 ] Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz, UESC, Bahia, Brasil
                [3 ] Laboratório de Pesquisa em Anemias, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, Bahia, Brasil
                [4 ] Fundação de Hematologia e Hemoterapia do Estado da Bahia, HEMOBA, Salvador, Bahia, Brasil
                Helen Keller International, SIERRA LEONE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-3000-1437
                Article
                PONE-D-19-29368
                10.1371/journal.pone.0228399
                6988974
                31995624
                52ffe708-c159-40cf-ae56-94b1d9f719d5
                © 2020 da Guarda et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 October 2019
                : 14 January 2020
                Page count
                Figures: 2, Tables: 4, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: 470959/2014-2
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: 405595/2016-6
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002322, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior;
                Award ID: 001
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002322, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior;
                Award ID: 001
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002322, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior;
                Award ID: 001
                Award Recipient :
                The work from MSG was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 470959/2014-2 and 405595/2016-6). SCMAY, RPS, and SPC received scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES), Finance Code 001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Proteins
                Hemoglobin
                Medicine and Health Sciences
                Hematology
                Medicine and Health Sciences
                Hematology
                Anemia
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Bone Marrow Cells
                Reticulocytes
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                Animal Cells
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                Medicine and Health Sciences
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