Studies In Sickle Cell Anemia Research Articles

A clinical study of sickle cell anemia and its management through Kiratatikta (Swertia chirayata) Ghanvati and Guduchi (Tinospora Cordifolia) Ghanvati

Introduction and Aim: Sickle cell anemia (SCA) is a genetic condition of mutation of beta globin chain and has been acknowledged to have a global public health impact. This disease is very common among many tribal and backward populations in India. In the central part of India its prevalence varies from 10-40% and in western area of Odisha varying from 10-17%. It can be classified as two types of homozygous sickle cell disease and heterozygous sickle cell trait. In Classical Ayurveda texts word to word correlation with SCA is not found. Clinical features of SCA correspond and are in line with Sannipataja Pandu Roga as described in classical texts. In the present work, a scientific effort was made for management of sickle cell disease through Ayurvedic interventions.
 
 Materials and Methods: A prospective clinical study was carried out in a total of thirty (30) patients of both sexes and randomly registered according to the clinical features of SCA from OPD and IPD of Government Ayurvedic College hospital, Bilaspur, Chhattisgarh. After assessment of subjective and objective criteria Kiratatikta Ghanvati and Guduchi Ghanvati were given 500 mg. each drug after meal with suitable fluid twice a day for a period of two months. Efficacy of therapy was inferred in 15 days interval and evaluated statistically by student’s paired ‘t’ test.
 
 Results: The overall improvement was assessed after study. The mean score before treatment was 3.53 while the mean score after treatment was 1.52. The statistical evaluation revealed that the mean difference was ± 2.01, SD±0.85, SE± 0.22 and t value 8.803. Trial medications were statistically highly significant with p<0.001.
 
 Conclusion: From the present study, it can be concluded that the trial drugs are very effective in the management of SCA; they reduce the subjective and objective parameters and its complications.

Disease genotype, haplotypes, diagnosis and associated studies in sickle cell anemia

Sickle cell anemia is a type of hemoglobinopathy characterized by a specific mutation in the beta globin gene with the consequent generation of an unstable hemoglobin that crystallizes in a state of hypoxia. This causes a change in the structure of the red blood cell, which ends up producing vaso-occlusion with the corresponding clinical complications for the patient. Worldwide, various diagnostic tests have been developed that allow the appropriate approach to the affected patient. These include techniques for the determination of hemoglobin and the use of molecular markers, among others. There are new therapeutic alternatives to the use of hydroxyurea and L-glutamine, such as the use of gene therapy tools. The most recent experimental trials are exploring gene editing techniques.

A Pilot Study of Sickle Cell Anemia in the Belizean Population

Background: Sickle Cell Anemia (Sickle Cell Disease) is an inherited disease resulting from a genetic mutation in the hemoglobin protein found in red blood cells. Screening is a requirement in the United States and in U.S. territories, and is considered a component of routine prenatal care. In resource limited countries such as Belize, there are no screening programs in place for testing newborns for Sickle Cell Anemia, and the disease is largely undefined. Children often go undiagnosed until they exhibit clinical symptoms. Untreated Sickle Cell Anemia in children under the age of 5 can lead to poor clinical outcomes. Oftentimes, those suspected of having the disease obtain diagnostic testing from a foreign country, and the test frequently used is the Sickle Prep Test. While the Sickle Prep Test is able to identify the presence of hemoglobin mutations, it cannot differentiate between sickle cell disease and sickle cell trait, a distinction which has profound clinical implications. A new technology, the Sickle SCAN test, utilizes a chromatographic, immunologic approach to qualitatively identify the presence of select variants of the hemoglobin protein (HbS, HbA, HbC), thereby allowing clinicians to differentiate between sickle cell disease and sickle cell trait. This test is a powerful tool that it is cost effective and timely; it does not require complicated testing equipment, and can disclose one's hemoglobin genetic profile in under 6 minutes. Methods: 87 patients were enrolled and tested for sickle cell disease and sickle cell trait in the towns of Dangriga and Hopkins, Belize. Testing took place over the course of 4 days. A survey was administered to collect key demographic information and information regarding participant's knowledge about Sickle Cell Anemia, past diagnosis, and family history of disease. Results: 13% were found to have sickle cell disease (n=12), and 25% were found to have the trait (n=22). For those with the disease or trait, the majority were found to belong to the Garifuna ethnic group. 26% of the participants had no knowledge of Sickle Cell Anemia. It was also reported that 51% had a family member with the disease, and 23% were unsure whether a family member had the disease.Conclusions: This pilot study demonstrates the feasibility ofusing the Sickle SCAN test to gather knowledge about the prevalence of Sickle Cell Anemia in a population where the disease remains largely undocumented. DisclosuresNo relevant conflicts of interest to declare.

Study of sickle cell anemia in females of Maharashtra population

Study of sickle cell anemia in females of Maharashtra population

Comparative study of sickle cell anemia and hemoglobin SC disease: clinical characterization, laboratory biomarkers and genetic profiles

BackgroundIn this study, we evaluate the association of different clinical profiles, laboratory and genetic biomarkers in patients with sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in attempt to characterize the sickle cell disease (SCD) genotypes.MethodsWe conducted a cross-sectional study from 2013 to 2014 in 200 SCD individuals (141 with SCA; 59 with HbSC) and analyzed demographic data to characterize the study population. In addition, we determined the association of hematological, biochemical and genetic markers including the βS-globin gene haplotypes and the 3.7 Kb deletion of α-thalassemia (−α3.7Kb-thal), as well as the occurrence of clinical events in both SCD genotypes.ResultsLaboratory parameters showed a hemolytic profile associated with endothelial dysfunction in SCA individuals; however, the HbSC genotype was more associated with increased blood viscosity and inflammatory conditions. The BEN haplotype was the most frequently observed and was associated with elevated fetal hemoglobin (HbF) and low S hemoglobin (HbS). The -α3.7Kb-thal prevalence was 0.09 (9%), and it was associated with elevated hemoglobin and hematocrit concentrations. Clinical events were more frequent in SCA patients.ConclusionsOur data emphasize the differences between SCA and HbSC patients based on laboratory parameters and the clinical and genetic profile of both genotypes.

Study of Sickle Cell Anemia with Clinical and Hematological Correlation (Provincial Hospital EL Idrissi, Morocco)

Sickle cell anemia is an autosomal recessive genetic disease by mutation of the β globin gene. This mutation induces the synthesis of abnormal hemoglobin (Hb) HbS, Mainly responsible for all clinical manifestations vaso-occlusives and chronic hemolysis with variable anemia. The objective of this study is the determination profile of haematological parameters of sickle cell children of the province of Kenitra (Morocco). In order to know the usual values and the particularities which are its own, we have observed that 50% of sickle cell children in our case study have severe anemia and 84% in patients aged 5 to 11 years. In addition, there is no significant difference among gender. The cases of hemoglobinosis S are divided into: Homozygous hemoglobinosis S (43%), Heterozygous sickle cell disease (17%), Hemoglobinosis S associated with alpha-thalassemia (1%), Hemoglobinosis S composite heterozygosity S/beta-thalassemia (5%), S/PHHF composite heterozygosity (6%), eventually composite heterozygosity S/beta+ thalassemia (28%). Homozygous sickle cell children have a long hospital stay, the highest number of hospitalizations and very severe sickle cell syndromes compared to the other phenotypic status of our population.

107. Ultrasound investigations in sickle cell anemia. Initial assessment and follow up

This study was proposed to compare two different equipment: TCD (trans-cranial doppler) and TCCS (transcranial color-coded sonography) with or without using the angular correction, in a group of patients with the sickle cell anemia in order to identify the most suitable technique for the sampling of blood velocity (TAMM). 35 pediatric patients without previus history of neurological disease or transfusion were enrolled. Arteries examined were the middle cerebral artery, the anterior cerebral artery, the posterior cerebral and the basilar arteries. TAMM values greater than 200 cm/s identify patients at high risk of stroke who are candidates for transfusion therapy. Our study demonstrated that there was a good correlation between TCCS and TCD. In addition, we found that if applied the angular correction to the TCCS increases the number of false-positive doppler examination. According to our study, we recommend to perform an initial assessment of the intracranial circulation with a method that allows to have morphological information, without the application of the angular correction. Indeed, the study of sickle cell anemia is complicated by the peculiar small diameter of the arteries and numerous variant of the circle of Willis.

Transcranial Doppler sonography in children with sickle cell disease and silent ischemic lesions

Sickle cell disease (SCD) is considered the most frequent cause of stroke in childhood. According to the STOP (stroke prevention trial in sickle cell anemia study) criteria, patients with abnormal values (>200 cm/s) of time-averaged mean velocities of maximum blood flow (TAMM), detected by transcranial Doppler sonography (TCD), should undergo blood transfusion in order to reduce the risk of ischemic stroke. However, patients with normal TAMM might harbor silent strokes on magnetic resonance imaging (MRI) scan. Our aim was to verify whether SCD patients with normal velocities but with a significant side-to-side asymmetry of TAMM are more prone to develop silent strokes. Thirty-one consecutive SCD patients, (15 females; mean age: 9.23 ± 3.66 years), categorized as “normal” according to the STOP protocol (<170 cm/s) and without a history of blood transfusions and TIA/stroke, underwent a cerebral MRI scan and complete TCD evaluation in order to detect significant asymmetries in the main intracranial arteries. Then, we subdivided this cohort into two groups according to the detection of TAMM asymmetry: “normal and symmetric” (NS), “normal and asymmetric” (NA). We found 13/31 patients (41.9%) harboring a significant TAMM asymmetry (NA group), while brain MRI detected silent ischemic lesions in 13/31 (41.9%) patients. No significant differences were found between NA and NS regarding silent strokes frequencies (Chi-square test with continuity correction, χ 2 = 0.598), lesion number ( t -student test, p = 0.09) and lesion burden ( t -student test, p = 0.227). According to our study, TAMM asymmetry is not a significant predictor of silent cerebral ischemia.

Entre negros e miscigenados: a anemia e o traço falciforme no Brasil nas décadas de 1930 e 1940

Aborda os estudos médicos e científicos sobre a anemia falciforme publicados no Brasil nas décadas de 1930 e 1940. A miscigenação foi apontada, pela maioria dos médicos e cientistas, como interferência significativa na epidemiologia da doença no país. Destaca a atuação do hematologista do Instituto Oswaldo Cruz Ernani Martins da Silva, que efetuou análises sanguíneas no interior no Brasil para determinar os grupos populacionais miscigenados e puros, baseado na identificação de hemácias falciformes e da distribuição racial dos grupos sanguíneos. Analisam-se as ambivalências existentes na associação entre a anemia falciforme e 'raça negra' durante os anos de 1930 e 1940 no Brasil.

50 Years Ago in The Journal of Pediatrics: Studies in Sickle Cell Anemia. XVI. Sudden Death During Sickle Cell Anemia Crises in Young Children

50 Years Ago in The Journal of Pediatrics: Studies in Sickle Cell Anemia. XVI. Sudden Death During Sickle Cell Anemia Crises in Young Children

Genome-wide association studies and the genetic dissection of complex traits.

The availability of affordable high throughput technology for parallel genotyping has opened the field of genetics to genome-wide association studies (GWAS), and in the last few years hundreds of articles reporting results of GWAS for a variety of heritable traits have been published. What do these results tell us? Although GWAS have discovered a few hundred reproducible associations, this number is underwhelming in relation to the huge amount of data produced, and challenges the conjecture that common variants may be the genetic causes of common diseases. We argue that the massive amount of genetic data that result from these studies remains largely unexplored and unexploited because of the challenge of mining and modeling enormous data sets, the difficulty of using nontraditional computational techniques and the focus of accepted statistical analyses on controlling the false positive rate rather than limiting the false negative rate. In this article, we will review the common approach to analysis of GWAS data and then discuss options to learn more from these data. We will use examples from our ongoing studies of sickle cell anemia and also GWAS in multigenic traits.

High oxygen environment during pregnancy rescues sickle cell anemia mice from prenatal death

Several mouse models of sickle cell disease have been developed for the study of the pathophysiology of sickle cell disease and the investigation of drug and gene therapies. In previous years, we produced a sickle cell anemia mouse model in which the endogenous mouse α- and β-globin genes were knocked out and replaced by the human α- and β s-globin transgenes. The β s-globin gene was contained in a 240 kb YAC that preserved the entire native genomic context of the β-globin locus. These mice have hemolytic anemia, reticulocytosis and irreversible sickle cells in the peripheral blood, as well as other pathological features of sickle cell disease. However, in the embryo, the γ-globin, like the mouse embryonic globin, declined quickly, and was replaced by β s-globin expression from 12 days of gestation. The low level of fetal hemoglobin expression in utero led to intrauterine sickling and fetal death so that very few live-born sickle cell anemia mice could be obtained. To rescue these mice from intrauterine death, we investigated the effect of placing the pregnant mothers in a high O 2 environment. From the tenth day of gestation onwards, we placed the mothers into a chamber containing 50% O 2 and kept them with the newborn pups in it for another 10 days after birth. The frequency of sickle cell anemia mice we obtained was increased from less than 2% to 35%. The survived sickle cell anemia mice develop congestion, atrophy, and infarcts in multiple organs similar to those found in patients with sickle cell disease. We conclude that a high oxygen environment can be used to obtain more sickle cell anemia mice in those models that have a high perinatal mortality. The higher yield of these mice has facilitated physiological and therapeutic studies of sickle cell anemia.

High Oxygen Environment during Pregnancy Rescues Sickle Cell Animia Mouse from Prenatal Death.

Several mouse models for sickle cell disease have been developed for the studies of the pathophysiology of sickle cell disease and the investigations of drug and gene therapies. In previous years, we have also succeeded in producing a sickle cell anemia mouse model. In this model the endogenous mouse α and β globin genes were knocked out and replaced by the human α and βs globin transgenes. The βs globin gene is contained in a 240kb YAC that preserves the entire native genomic context of the β-globin locus. These mice have anemia, reticulocytosis and irreversible sickle cells in the peripheral blood, as well as other pathological features of sickle cell disease. However, their γ globin switches to βs globin expression from around 12 days of gestation. The low level of fetal hemoglobin expression in utero led to intrauterine sickling and fetal death so that very few live-born sickle cell anemia mice could be obtained. To rescue these mice from intrauterine death we investigated the effect of placing the pregnant mothers into a high O2 environment. From the tenth day of gestation onwards, we placed the mothers into a chamber containing 50% O2 and kept the newborn pups in it for another 10 days after birth. The frequency of sickle cell anemia mice we obtained was increased from 0.2% to 32%. Moreover, 55% to 88% of the newborn sickle cell anemia mice survived in the oxygen treated group, whereas none of the sickle cell anemia mice survived in regular air breeding conditions. The survived sickle cell anemia mice develop congestion, atrophy, and infarcts in multiple organs by histological analysis. These pathological finding are very similar to those find in patients with sickle cell disease. We conclude that a high oxygen environment can be used to obtain more sickle cell anemia mice in those models that have a high perinatal mortality. The higher yield of these mice will facilitate physiological and therapeutic studies of sickle cell anemia.

Thalassemia and Learning: Neurocognitive Functioning in Children

As more effective management and even cure of thalassemia become possible, attention is beginning to be directed to the potential neurologic and resulting neurocognitive effects of this illness on adults and children. Recent studies indicate that for adults with beta-thalassemia major and intermedia, and for children with sickle beta-thalassemia (Sbeta-thalassemia), there is a substantial risk for silent brain infarcts that may be associated with neurocognitive impairment similar to that reported for children with sickle cell anemia. Here the available literature in this area is reviewed and the limited outcomes are compared with those available from large, multicenter longitudinal studies of sickle cell anemia. On the basis of these comparisons, it is recommend that children with thalassemia be screened for specific neuropsychological impairments and that they be provided early intervention and special education access as available under the Individuals with Disabilities Education Act (IDEA) or the 504 Regulations of the Rehabilitation Act of 1973.

From a dry bone to a genetic portrait: a case study of sickle cell anemia.

The potential and reliability of DNA analysis for the identification of human remains are demonstrated by the study of a recent bone sample, which represented a documented case of sickle cell anemia. beta-globin gene sequences obtained from the specimen revealed homozygosity for the sickle cell mutation, proving the authenticity of the retrieved residual DNA. Further investigation of mitochondrial and Y chromosome DNA polymorphic markers indicated that this sample came from a male of maternal West African (possibly Yoruban) and paternal Bantu lineages. The medical record, which became available after the DNA analyses had been completed, revealed that it belonged to a Jamaican black male. These findings are consistent with this individual being a descendent of Africans brought to Jamaica during the trans-Atlantic slave trade. This study exemplifies how a "reverse population genetics" approach can be applied to reconstruct a genetic profile from a bone specimen of an unknown individual.

The Expression of Pathologic Reticulocyte Adhesion Proteins in Premature Infants and its Role in Necrotizing Enterocolitis. † 958

Prematurity is recognized as the primary risk factor which predisposes infants to necrotizing enterocolitis (NEC). However, the pathophysiology of NEC is poorly understood. Recent studies in sickle cell anemia suggest that the expression of adhesive proteins on reticulocytes may result in pathologic red cell binding to endothelial cells (EC). The resultant vascular occlusion may occur via an α4β1 integrin binding to the TNF induced EC ligand VCAM-1. To address whether this mechanism may play a role in NEC, we determined whether erythrocytes from premature infants express theα4β1 integrin complex. Blood specimens from premature infants (mean age 28 wks, range 23-32 wks) were examined for expression of α4β1 utilizing flow cytommetry. Bowel specimens from patients with NEC were examined for VCAM-1 by immunohistochemistry. Data are expressed as mean± SEM. Statistical analysis was performed by Student's unpaired t-test. Premature infants (n=40) had both increased circulating reticulocytes andα4β1 expression verses normal term control infants (n=20, p<.001). This expression was consistent with the integrin expression observed in patients with NEC (n=20). Table

Augmentation of fetal hemoglobin (HbF) synthesis in culture by human erythropoietic precursors in the marrow and peripheral blood: studies in sickle cell anemia and nonhemoglobinopathic adults

We cultured marrow and peripheral blood erythropoietic precrusors in methylcellulose clonal assay and measured the synthetic rates of HbA, A2, F, and S in patients with and without sickle cell anemia. Hb was labeled with 14C-amino acid in culture, separated by slab gel isoelectric focusing techniques, and quantitated by autoradiographic methods. Comparison of marrow late (CFU-E) and early (BFU-E) precursors from patients without hemoglobinopathies showed that preferential synthesis of HbF is limited to early precursors. Simultaneous examinations of Hb synthesis by blood and marrow early erythropoietic precursors confirmed the similarity of the biosynthetic capabilities of the precursors from the two sources. Increasing concentrations of erythropoietin (Ep) in culture corresponded with increases in the percentages of HbF synthesized by blood BFU-E of normal individuals. HbF biosynthesis by blood BFU-E from sickle cell anemia patients was significantly higher than that synthesized by nonanemic individuals and showed significant individual variations. HbF synthesis in patients with sickle cell anemia was partially dependent on Ep concentrations in culture. Cell culture of circulating erythropoietic precursors in man appears to provide a unique tool for studying the control mechanisms of Hb synthesis in man.

Augmentation of Fetal Hemoglobin (HbF) Synthesis in Culture by Human Erythropoietic Precursors in the Marrow and Peripheral Blood: Studies in Sickle Cell Anemia and Nonhemoglobinopathic Adults

We cultured marrow and peripheral blood erythropoietic precrusors in methylcellulose clonal assay and measured the synthetic rates of HbA, A2, F, and S in patients with and without sickle cell anemia. Hb was labeled with 14C-amino acid in culture, separated by slab gel isoelectric focusing techniques, and quantitated by autoradiographic methods. Comparison of marrow late (CFU-E) and early (BFU-E) precursors from patients without hemoglobinopathies showed that preferential synthesis of HbF is limited to early precursors. Simultaneous examinations of Hb synthesis by blood and marrow early erythropoietic precursors confirmed the similarity of the biosynthetic capabilities of the precursors from the two sources. Increasing concentrations of erythropoietin (Ep) in culture corresponded with increases in the percentages of HbF synthesized by blood BFU-E of normal individuals. HbF biosynthesis by blood BFU-E from sickle cell anemia patients was significantly higher than that synthesized by nonanemic individuals and showed significant individual variations. HbF synthesis in patients with sickle cell anemia was partially dependent on Ep concentrations in culture. Cell culture of circulating erythropoietic precursors in man appears to provide a unique tool for studying the control mechanisms of Hb synthesis in man.

Prospective study of sickle cell anemia in infancy

Twelve infants with sickle cell anemia identified in the course of a cord blood screening program have been followed prospectively for up to three years of age. The development of hemolytic anemia paralleled the postnatal decline in fetal hemoglobin and was evident in all infants by 12 weeks of age. Vasoocclusive episodes occurred in more than half the infants and seven aplastic crises were documented in four patients. Febrile illnesses were common and one of the twelve infants developed pneumococcal sepsis. This study also demonstrated that functional asplenia is an acquired defect in sickle cell disease. The onset of functional asplenia was documented with splenic scans in six of the nine infants followed for more than one year after birth. There have been no deaths in this series.

STUDIES IN SICKLE CELL ANEMIA. XXII. CLINICAL MANIFESTATIONS OF SICKLE CELL ANEMIA DURING THE FIRST TWO YEARS OF LIFE.

STUDIES IN SICKLE CELL ANEMIA. XXII. CLINICAL MANIFESTATIONS OF SICKLE CELL ANEMIA DURING THE FIRST TWO YEARS OF LIFE.