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Gregory J Kato, Frédéric B Piel, Clarice D Reid, Marilyn H Gaston, Kwaku Ohene-Frempong, Lakshmanan Krishnamurti, Wally R Smith, Julie A Panepinto, David J Weatherall, Fernando F Costa, Elliott P Vichinsky
Sickle cell disease (SCD) is a group of inherited disorders caused by mutations in HBB, which encodes haemoglobin subunit β. The incidence is estimated to be between 300,000 and 400,000 neonates globally each year, the majority in sub-Saharan Africa. Haemoglobin molecules that include mutant sickle β-globin subunits can polymerize; erythrocytes that contain mostly haemoglobin polymers assume a sickled form and are prone to haemolysis. Other pathophysiological mechanisms that contribute to the SCD phenotype are vaso-occlusion and activation of the immune system...
March 15, 2018: Nature Reviews. Disease Primers
Hitomi Hosoya, Jeffrey Levine, Peter Abt, David Henry, David L Porter, Saar Gill
Sickle-cell disease (SCD) leads to recurrent vaso-occlusive crises, chronic end-organ damage, and resultant physical, psychological, and social disabilities. Although hematopoietic stem-cell transplantation (HSCT) is potentially curative for SCD, this procedure is associated with well-recognized morbidity and mortality and thus is ideally offered only to patients at high risk of significant complications. However, it is difficult to identify patients at high risk before significant complications have occurred, and once patients experience significant organ damage, they are considered poor candidates for HSCT...
March 13, 2018: Blood Advances
Isabela Cristina Cordeiro Farias, Taciana Furtado Mendonça-Belmont, Andreia Soares da Silva, Kleyton Palmeira do Ó, Felipe Ferreira, Fernanda Silva Medeiros, Luydson Richardson da Silva Vasconcelos, Marcos André Cavalcanti Bezerra, Aderson da Silva Araújo, Patricia Muniz Mendes Freire de Moura, Betânia Lucena Domingues Hatzlhofer, Ana Claudia Mendonça Dos Anjos, Maria do Socorro de Mendonça Cavalcanti
The SOD2 polymorphism Val16Ala T→C influences the antioxidative response. This study investigated the association of the SOD2 polymorphism and superoxide dismutase (SOD) activity with the vaso-occlusive crisis (VOC) and acute splenic sequestration (ASS) in children with sickle cell anemia (SCA). One hundred ninety-five children with SCA aged 1-9 years old were analyzed. The TC and CC genotypes were associated with lower SOD activity compared with the TT genotype (p=0.0321; p=0.0253, respectively). Furthermore, TC and CC were more frequent in patients with VOC or ASS (p=0...
2018: Mediterranean Journal of Hematology and Infectious Diseases
Benjamin Zielonka, Alan R Cohen, Kim Smith-Whitley, Bhavya S Doshi
Although musculoskeletal pain in patients with sickle cell disease (SCD) is most frequently the result of vaso-occlusive episodes, clinicians often consider other etiologies including osteomyelitis, avascular necrosis, and trauma. In this study, we report the case of a young female with SCD with hip and back pain secondary to a nontraumatic iliopsoas periosteal hematoma with evidence of adjacent bone infarction. The pathophysiology, diagnostic considerations, and management of periosteal hematomas in SCD are reviewed...
March 12, 2018: Pediatric Blood & Cancer
Ilknur Kozanoglu, Hakan Ozdogu
Sickle cell disease (SCD) is a life-threatening chronic condition primarily caused by genetic mutation. The disease is characterized by intermittent vaso-occlusive events and chronic hemolytic anemia. Acute complications in patients with SCD are difficult to manage due to the pathophysiological nature of the disease. Transfusion therapy is the cornerstone of management of acute complications and significantly reduces SCD morbidity and mortality. Red cell exchange (RCE), which is characterized by low iron accumulation and volume overload, has been widely used for transfusion therapy in recent years...
February 21, 2018: Transfusion and Apheresis Science
Milton Packer
Although dipeptidyl peptidase (DPP)-4 inhibitors have been reported to have a neutral effect on thromboembolic vaso-occlusive events in large-scale trials, they act to potentiate several endogenous peptides that can exert deleterious cardiovascular effects. Experimentally, DPP-4 inhibitors may augment the ability of glucagon-like peptide-1 to stimulate cyclic adenosine monophosphate in cardiomyocytes, and potentiation of the effects of stromal cell-derived factor-1 by DPP-4 inhibitors may aggravate cardiac fibrosis...
March 1, 2018: JACC. Heart Failure
Cheryl L Maier, Phillip J Gross, Christina L Dean, Satheesh Chonat, Andrew Ip, Morgan McLemore, Fuad El Rassi, Sean R Stowell, Cassandra D Josephson, Ross M Fasano
BACKGROUND: Fever accompanying vaso-occlusive crisis is a common presentation in patients with sickle cell disease (SCD) and carries a broad differential diagnosis. Here, we report a case of transfusion-transmitted malaria in a patient with SCD presenting with acute vaso-occlusive crisis and rapidly decompensating to multisystem organ failure (MSOF). CASE REPORT: An 18-year-old African American male with SCD was admitted after multiple days of fever and severe generalized body pain...
March 9, 2018: Transfusion
Christine C Helms, Mark T Gladwin, Daniel B Kim-Shapiro
Erythrocytes regulate vascular function through the modulation of oxygen delivery and the scavenging and generation of nitric oxide (NO). First, hemoglobin inside the red blood cell binds oxygen in the lungs and delivers it to tissues throughout the body in an allosterically regulated process, modulated by oxygen, carbon dioxide and proton concentrations. The vasculature responds to low oxygen tensions through vasodilation, further recruiting blood flow and oxygen carrying erythrocytes. Research has shown multiple mechanisms are at play in this classical hypoxic vasodilatory response, with a potential role of red cell derived vasodilatory molecules, such as nitrite derived nitric oxide and red blood cell ATP, considered in the last 20 years...
2018: Frontiers in Physiology
Rustam Al-Shahi Salman, Martin S Dennis, Gordon D Murray, Karen Innes, Jonathan Drever, Lynn Dinsmore, Carol Williams, Philip M White, William N Whiteley, Peter A G Sandercock, Cathie L M Sudlow, David E Newby, Nikola Sprigg, David J Werring
BACKGROUND: For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. METHODS/DESIGN: The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom...
March 5, 2018: Trials
Marie-Laure Lalanne-Mistrih, Philippe Connes, Yann Lamarre, Nathalie Lemonne, Marie-Dominique Hardy-Dessources, Vanessa Tarer, Maryse Etienne-Julan, Dominique Mougenel, Benoît Tressières, Marc Romana
BACKGROUND: The pathophysiology of sickle cell disease (SCD) and the variability of its clinical expression remain not fully understood, whether within or between different SCD genotypes. Recent studies have reported associations between lipid levels and several SCD complications. If lipid levels have been previously described as low in sickle cell anemia (SCA), few data have been provided for sickle cell SC disease (SCC). We designed our epidemiological study to isolate lipid levels and profiles by genotype in Guadeloupian cohorts of SCA and SCC adult patients, at steady state...
March 5, 2018: Lipids in Health and Disease
Nitya Bakshi, Ines Lukombo, Inna Belfer, Lakshmanan Krishnamurti
Introduction: Sickle cell disease (SCD) is an inherited blood disorder characterized by abnormally shaped sickle cells. The hallmark of this disease is intermittent, painful vaso-occlusive episodes (VOE), but a subset of individuals with SCD experience chronic pain. The mechanism of transition to chronic pain is not well understood in SCD, but there is evidence of altered pain processing in individuals with SCD. The impact of VOE on pain sensitivity is not established. The objective of this study was to determine the feasibility and tolerability of quantitative sensory testing (QST) in SCD following a VOE to better understand the contribution of VOE to the development of chronic pain...
2018: Journal of Pain Research
Rosario Di Maggio, Matthew M Hsieh, Xiongce Zhao, Giuseppina Calvaruso, Paolo Rigano, Disma Renda, John F Tisdale, Aurelio Maggio
In sickle cell disease (SCD), hydroxyurea (HU) treatment decreases the number of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) by increasing fetal hemoglobin (HbF). Data are lacking regarding the frequency of HU dose modification or whether sub-therapeutic doses (<15 mg/kg/day) are beneficial. We reviewed the medical records of 140 patients from 2010 to 2014. The laboratory parameters and SCD complications were compared between the first and last visits based on HU use. Fifty patients (36%) never took HU or suspended HU ("no HU" group)...
February 28, 2018: International Journal of Molecular Sciences
Lynn Calvin Shaw, Sergio Li Calzi, Nan Li, Leni Moldovan, Nilanjana Sengupta-Caballero, Judith Lindsey Quigley, Mircea Ivan, Bokkyoo Jun, Nicolas G Bazan, Michael Edwin Boulton, Julia Busik, Josef Neu, Maria B Grant
Purpose: Low levels of the long chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) have been implicated in retinopathy of prematurity (ROP). However, oral DHA suffers from poor palatability and is associated with increased bleeding in premature infants. We asked whether oral administration of the neutraceutical arginine-glutamine (Arg-Glu) could increase retinal DHA and improve outcomes in a mouse model of oxygen-induced retinopathy (OIR). Methods: Postnatal day 7 (P7) pups were maintained at 75% oxygen for 5 days and then returned to room air on P12...
February 1, 2018: Investigative Ophthalmology & Visual Science
Marina Viegas Moura Rezende Ribeiro, João Vitor de Omena Jucá, Anna Luyza Correia Dos Santos Alves, Caio Victor Oliveira Ferreira, Fabiano Timbó Barbosa, Êurica Adélia Nogueira Ribeiro
Hemoglobinopathies are a group of hereditary diseases that cause quantitative or qualitative changes in the shape, function or synthesis of hemoglobin. One of the most common is sickle cell anemia, which, due to sickling of erythrocytes, causes vaso-occlusive phenomena. Among the possible ocular manifestations, the most representative is retinopathy, which can lead to blindness if left untreated. Therefore, periodic ophthalmologic monitoring of these patients is important for early diagnosis and adequate therapeutic management, which can be done localy by treating the lesions in the eyes, or systemically...
December 2017: Revista da Associação Médica Brasileira
Santosh L Saraf, Justin R Sysol, Alexandru Susma, Suman Setty, Xu Zhang, Krishnamurthy P Gudehithlu, Jose A L Arruda, Ashok K Singh, Roberto F Machado, Victor R Gordeuk
Homozygosity for the hemoglobin (Hb) S mutation (HbSS, sickle cell anemia) results in hemoglobin polymerization under hypoxic conditions leading to vaso-occlusion and hemolysis. Sickle cell anemia affects 1:500 African Americans and is a strong risk factor for kidney disease, although the mechanisms are not well understood. Heterozygous inheritance (HbAS; sickle cell trait) affects 1:10 African Americans and is associated with an increased risk for kidney disease in some reports. Using transgenic sickle mice, we investigated the histopathologic, ultrastructural, and gene expression differences with the HbS mutation...
February 2, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Chantal Lagresle-Peyrou, François Lefrère, Elisa Magrin, Jean-Antoine Ribeil, Oriana Romano, Leslie Weber, Alessandra Magnani, Hanem Sadek, Clémence Plantier, Aurélie Gabrion, Brigitte Ternaux, Tristan Félix, Chloé Couzin, Aurélie Stanislas, Jean-Marc Tréluyer, Lionel Lamhaut, Laure Joseph, Marianne Delville, Annarita Miccio, Isabelle André-Schmutz, Marina Cavazzana
Sickle cell disease is characterized by chronic anaemia and vaso-occlusive crises, which eventually lead to multi-organ damage and premature death. Haematopoietic stem cell transplantation is the only curative treatment but it is limited by toxicity and poor availability of HLA-compatible donors. A gene therapy approach based on the autologous transplantation of lentiviral-corrected haematopoietic stem and progenitor cells was shown to be efficacious in one patient. However, alterations of the bone marrow environment and the red blood cells' properties hamper the harvesting and immunoselection of patient stem cells from bone marrow...
February 22, 2018: Haematologica
Dipty Jain, Dipika Mohanty
PURPOSE OF REVIEW: In the past, milder clinical manifestations of sickle cell disease (SCD) have been described from India. However, recent data from some parts of India suggest that the severity of the disease can be compared to that of African phenotypes. This review therefore describes the varied clinical manifestation of SCD, the success of newborn screening programme, prenatal diagnosis and low dose hydroxyurea therapy in India. RECENT FINDINGS: The varied clinical manifestations such as anemia, vaso-occlusive crisis, acute chest syndrome, renal involvement, stroke and so on vary from one part of the country to the other and also among different communities of India...
February 19, 2018: Current Opinion in Hematology
Hui Zhong, Karina Yazdanbakhsh
PURPOSE OF REVIEW: Hemolytic anemias caused by premature destruction of red blood cells occur in many disorders including hemoglobinopathies, autoimmune conditions, during infection or following reaction to drugs or transfusions. Recent studies which will be reviewed here have uncovered several novel mechanisms by which hemolysis can alter immunological functions and increase the risk of severe complications in hemolytic disorders. RECENT FINDINGS: Plasma-free heme can induce the formation of neutrophil extracellular traps (NETs) through reactive oxygen species signaling...
February 15, 2018: Current Opinion in Hematology
Céline Renoux, Philippe Joly, Camille Faes, Pauline Mury, Buse Eglenen, Mine Turkay, Gokce Yavas, Ozlem Yalcin, Yves Bertrand, Nathalie Garnier, Daniela Cuzzubbo, Alexandra Gauthier, Marc Romana, Berenike Möckesch, Giovanna Cannas, Sophie Antoine-Jonville, Vincent Pialoux, Philippe Connes
OBJECTIVES: To investigate the associations between several sickle cell disease genetic modifiers (beta-globin haplotypes, alpha-thalassemia, and glucose-6-phosphate dehydrogenase deficiency) and the level of oxidative stress and to evaluate the association between oxidative stress and the rates of vaso-occlusive events. STUDY DESIGN: Steady-state oxidative and nitrosative stress markers, biological variables, genetic modulators, and vaso-occlusive crisis events requiring emergency admissions were measured during a 2-year period in 62 children with sickle cell anemia (58 SS and 4 Sβ 0 )...
February 13, 2018: Journal of Pediatrics
Farid Boulad, Tsiporah Shore, Koen van Besien, Caterina Minniti, Mihaela Barbu-Stevanovic, Sylvie Wiener Fedus, Fabiana Perna, June Greenberg, Danielle Guarneri, Vijay Nandi, Audrey Mauguen, Karina Yazdanbakhsh, Michel Sadelain, Patricia A Shi
Gene therapy for sickle cell disease is limited by the yield of hematopoietic progenitor cell harvest for transduction or gene editing. We therefore performed a Phase I dose-escalation study of the hematopoietic progenitor cell mobilizing agent plerixafor to evaluate the efficacy and safety of standard dosing on peripheral blood CD34+ cell mobilization. Of 15 patients enrolled to date, only one was chronically transfused and 10 were on hydroxyurea. Of 8 patients achieving a CD34+ cell concentration >30 cells/μl, 6 were on hydroxyurea...
February 1, 2018: Haematologica
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