scholarly journals The Fc Receptor Polymorphisms and Expression of Neutrophil Activation Markers in Patients with Sickle Cell Disease from Western India

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Harshada K. Kangne ◽  
Farah F. Jijina ◽  
Yazdi M. Italia ◽  
Dipti L. Jain ◽  
Anita H. Nadkarni ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Manifestations ◽  
Western India ◽  
Genotypic Frequency ◽  
Cell Disease ◽  
Activation Markers ◽  
Initiation And Propagation ◽  
Significant Difference ◽  
The Common

Objective. Sickle cell disease has variable clinical manifestations. Activation of neutrophils plays an important role in the initiation and propagation of vaso occlusive crises which can be analysed by determining the expression of neutrophil antigens such as CD16, CD32, and CD62L. The common FcγR polymorphisms (FcγRIIA and FcγRIIIB) are considered to influence clinical presentation. This study focuses on distribution of FcγR polymorphisms and their association with neutrophil activity among the patients from western India.Methods. In this paper 127 sickle cell anemia patients and 58 patients with sickle-β-thalassemia (median age12±8.58 years) with variable clinical phenotypes along with 175 normals were investigated. FcγRs polymorphisms were analysed by RFLP and AS-PCR. Activation of neutrophils was measured by flow cytometry.Results. The genotypic frequency of the H/R genotype of FcγRIIA and the NA1/NA1 genotype of FcγRIIIB was significantly decreased in patients compared to normals (P-0.0074,P-0.0471, resp.). We found a significant difference in the expression of CD32 and CD62L among the patients as against normals. A significantly higher expression of CD32 was seen in the milder patients with the H/H genotype (P-0.0231), whereas the expression of CD16 was higher in severe patients with the NA2/NA2 genotype (P-0.0312).Conclusion. The two FcγR polymorphisms had significant association with variable phenotypes of sickle cell disease. The expression of CD62L decreased in our patients indicating activation of neutrophils.

scholarly journals A study of clinical and hematological profile of children with sickle cell disease in a tertiary care hospital, Valsad, India

2017 ◽  
Vol 4 (4) ◽  
pp. 1317 ◽  
Author(s):  
Kinjal G. Patel ◽  
Chintu Chaudhari ◽  
Diwakar Sharma
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Tertiary Care ◽  
Morbidity And Mortality ◽  
Care Hospital ◽  
Age Group ◽  
Cell Disease ◽  
Significant Difference ◽  
The Common

Background: Sickle cell disease is commonly seen in rural population of south part of Gujarat in India. It is one of the common causes of recurrent hospitalization, morbidity and mortality in pediatric population. This study was therefore undertaken to evaluate the clinical profile of sickle cell disease in a tertiary care hospital.Methods: This was the prospective observational study done from November 2015 to October 2016. All the hospitalized diagnosed case of sickle cell disease and trait in age group of 6 months to 14 years were taken in this study. Sickle cell disease with some genetic or metabolic disease and sickle-beta-thalassemia patients were not included in this study.Results: Total 61 patients were admitted over a one year of study period, out of which 47 were sickle cell disease and 14 sickle cell trait patients. Morbidity events were commonly observed in 5-12 years of age groups (68.85%). Seasonal variation also observed, 47.54% of total cases are seen in winter season. Pain (60.65%) was the most common presenting symptom. Severe pallor (39.34%) and splenomegaly (24.59%) was the most common sign in both groups. Vaso-occlusive crisis (59.01%) was the most common morbidity event observed, of which abdominal pain was the most common site of pain involvement. On laboratory analysis, there was statistically significant difference observed in disease and trait. In patients with sickle cell disease acute painful crisis (59.57%) was the common morbidity event observed while in sickle cell trait patients acute febrile illness (71.42%) observed.Conclusions: Vaso-occlusive crisis is the commonest manifestation in pediatric age group. Comprehensive medical care and management is required to decrease the morbidity and mortality. 

Heme Concentration As a Biomarker of Sickle Cell Disease Severity: Its Role in Steady-State and in Crisis Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 975-975 ◽  
Author(s):  
Magda Oliveira Seixas Carvalho ◽  
Larissa Carneiro Rocha ◽  
João Henrique Oliveira Reis ◽  
Théo de Araújo Santos ◽  
Valma Maria Lopes do Nascimento ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Healthy Individuals ◽  
Cell Disease ◽  
High Concentration ◽  
Significant Difference ◽  
Free Heme

Abstract Background: Sickle cell disease (SCD) is a heredity group of anemia characterized by hemolysis, chronic inflammation, and vaso-occlusive/painful crisis. The heme is a product of erythrocytes' lyses and is increased in hemolytic diseases. Objectives: To investigate associations between hematological/biochemistry biomarkers and total plasma heme levels between SCD patients groups (in crisis and in steady-state) and healthy controls. To identify molecules related to hemolysis, inflammation, hepatic dysfunction, renal and lipid metabolism. Methods: We evaluated a total of 125 SCD steady-state patients, 22 SCD in crisis patients, and 32 healthy individuals age- and sex-matched with patients groups. Hematological analyses were performed by automatic cell counter, and hemoglobin profile by HPLC. Biochemistry analyses of inflammatory and infection markers, as well as lipid, hepatic, and kidney metabolism markers were investigated by immunochemistry assays. Plasma concentration of total free heme was measured by QuantiChrom Heme Assay Kit. Results: SCD patients groups (steady state and crisis) had higher heme concentration when compared to healthy individuals (p < 0.0001). However, significant difference of heme level was not finding in the comparison between SCD in steady state and SCD crisis patients groups. Biomarkers analyses of steady-state SCD patients showed negative correlation between heme levels and: red blood cell (r = -0.36, p<0.0001); hematocrit (r = -0.38, p <0.0001); hemoglobin (r = -0.34, p <0.0001); and HDL-C (r = -0.42, p <0.0001). Heme level showed positive correlation with: platelets (r = 0.35, p <0.0001); lactic dehidrogenase (r = 0.40, p <0.0001); reticulocytes count (r = 0.19, p =0.04); monocytes count (r = 0.36, p <0.0001); HbS concentration (r = 0.54, p <0.0001); total proteins (r = 0.22, p =0.01); AST (r = 0.41, p <0.0001); ALT (r = 0.18, p= 0.04); serum iron (r =0.21, p =0.03); total cholesterol (r = 0.23, p =0.01); LDL-C (r = 0.22, p= 0.02); VLDL-C (r = 0.65, p <0.0001); and triglycerides (r = 0.63, p <0.0001). In steady state SCD patients there was no difference of clinical manifestations history and heme levels. Conclusions: The finding of similar heme concentration between steady state and crisis SCD patients may be explained by the hyperhemolysis phenomenon, showing that even in steady-state, these patients continue to have hemolysis and generate heme and reactive oxygen species. It was also shown that high concentration of free heme increases hemolytic and inflammatory biomarkers, such as LDH, bilirubin's, reticulocytes count, and lipids, contributing to a severe clinical modulation of SCD. Disclosures No relevant conflicts of interest to declare.

scholarly journals Predictors of musculoskeletal manifestations in paediatric patients presenting with sickle cell disease at a tertiary teaching hospital in Lusaka, Zambia

2020 ◽  
Vol 1 (6) ◽  
pp. 175-181
Author(s):  
Raymond Mpanjilwa Musowoya ◽  
Patrick Kaonga ◽  
Alick Bwanga ◽  
Catherine Chunda-Lyoka ◽  
Christopher Lavy ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Teaching Hospital ◽  
Clinical Manifestations ◽  
Classification Systems ◽  
University Teaching ◽  
Cell Disease ◽  
Tertiary Teaching ◽  
Musculoskeletal Manifestations

Aims Sickle cell disease (SCD) is an autosomal recessive inherited condition that presents with a number of clinical manifestations that include musculoskeletal manifestations (MM). MM may present differently in different individuals and settings and the predictors are not well known. Herein, we aimed at determining the predictors of MM in patients with SCD at the University Teaching Hospital, Lusaka, Zambia. Methods An unmatched case-control study was conducted between January and May 2019 in children below the age of 16 years. In all, 57 cases and 114 controls were obtained by systematic sampling method. A structured questionnaire was used to collect data. The different MM were identified, staged, and classified according to the Standard Orthopaedic Classification Systems using radiological and laboratory investigations. The data was entered in Epidata version 3.1 and exported to STATA 15 for analysis. Multiple logistic regression was used to determine predictors and predictive margins were used to determine the probability of MM. Results The cases were older median age 9.5 (interquartile range (IQR) 7 to 12) years compared to controls 7 (IQR 4 to 11) years; p = 0.003. After multivariate logistic regression, increase in age (adjusted odds ratio (AOR) = 1.2, 95% confidence interval (CI) 1.04 to 1.45; p = 0.043), increase in the frequency of vaso-occlusive crisis (VOC) (AOR = 1.3, 95% CI 1.09 to 1.52; p = 0.009) and increase in percentage of haemoglobin S (HbS) (AOR = 1.18, 95% CI 1.09 to 1.29; p < 0.001) were significant predictors of MM. Predictive margins showed that for a 16-year-old the average probability of having MM would be 51 percentage points higher than that of a two-year-old. Conclusion Increase in age, frequency of VOC, and an increase in the percentage of HbS were significant predictors of MM. These predictors maybe useful to clinicians in determining children who are at risk. Cite this article: Bone Joint Open 2020;1-6:175–181.

scholarly journals Pregnancies and Neonatal Outcomes in Patients with Sickle Cell Disease (SCD): Still a (High-)Risk Constellation?

2021 ◽  
Vol 11 (9) ◽  
pp. 870
Author(s):  
Pia Proske ◽  
Laura Distelmaier ◽  
Carmen Aramayo-Singelmann ◽  
Nikolaos Koliastas ◽  
Antonella Iannaccone ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Neonatal Outcomes ◽  
University Hospital ◽  
High Rate ◽  
Successful Outcome ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Significant Difference ◽  
Tract Infections

Background: This monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany. Methods/Results: 46 pregnancies in 22 patients were followed. None of the patients died. In total, 35% (11/31) of pregnancies were preterm. 15 pregnancies in eight patients were conceived on hydroxycarbamide (HC), of which nine had a successful outcome and three were terminated prematurely. There was no difference regarding the rate of spontaneous abortions in patients receiving HC compared to HC-naive patients prior to conception. In patients other than HbS/C disease, pregnancies were complicated by vaso-occlusive crises (VOCs)/acute pain crises (APCs) (96%, 23/24); acute chest syndrome (ACS) (13%, 3/24), transfusion demand (79%, 19/24), urinary tract infections (UTIs) (42%, 10/24) and thromboembolic events (8%, 2/24). In HbS/C patients complications included: VOCs/APCs (43%, 3/7; ACS: 14%, 1/7), transfusion demand (14%, 1/7), and UTIs (14%, 1/7). Independent of preterm deliveries, a significant difference with respect to neonatal growth in favor of neonates from HbS/C mothers was observed. Conclusion: Our data support the results of previous studies, highlighting the high rate of maternal and fetal/neonatal complications in pregnant SCD patients.

scholarly journals Genome editing using CRISPR-Cas9 to create the HPFH genotype in HSPCs: An approach for treating sickle cell disease and β-thalassemia

2016 ◽  
Vol 113 (38) ◽  
pp. 10661-10665 ◽  
Author(s):  
Lin Ye ◽  
Jiaming Wang ◽  
Yuting Tan ◽  
Ashley I. Beyer ◽  
Fei Xie ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Genome Editing ◽  
Sickle Cell ◽  
Globin Gene ◽  
Autologous Transplantation ◽  
Clinical Manifestations ◽  
Fetal Hemoglobin ◽  
Compound Heterozygous ◽  
Cell Disease ◽  
Hematopoietic Stem

Hereditary persistence of fetal hemoglobin (HPFH) is a condition in some individuals who have a high level of fetal hemoglobin throughout life. Individuals with compound heterozygous β-thalassemia or sickle cell disease (SCD) and HPFH have milder clinical manifestations. Using RNA-guided clustered regularly interspaced short palindromic repeats-associated Cas9 (CRISPR-Cas9) genome-editing technology, we deleted, in normal hematopoietic stem and progenitor cells (HSPCs), 13 kb of the β-globin locus to mimic the naturally occurring Sicilian HPFH mutation. The efficiency of targeting deletion reached 31% in cells with the delivery of both upstream and downstream breakpoint guide RNA (gRNA)-guided Staphylococcus aureus Cas9 nuclease (SaCas9). The erythroid colonies differentiated from HSPCs with HPFH deletion showed significantly higher γ-globin gene expression compared with the colonies without deletion. By T7 endonuclease 1 assay, we did not detect any off-target effects in the colonies with deletion. We propose that this strategy of using nonhomologous end joining (NHEJ) to modify the genome may provide an efficient approach toward the development of a safe autologous transplantation for patients with homozygous β-thalassemia and SCD.

Evaluation of Intravenous Diphenhydramine Use in Patients with Sickle Cell Vaso-Occlusive Crisis

2020 ◽  
pp. 001857872095417
Author(s):  
Katherine Rector ◽  
Shelby Merchant ◽  
Rachel Crawford ◽  
Justin R. Arnall ◽  
James Symanowski ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Sickle Cell ◽  
Cell Disease ◽  
Median Length ◽  
Significant Difference ◽  
Oral Group ◽  
Icd 10 ◽  
Secondary Endpoints ◽  
Group 2

Purpose: To compare the incidence of oversedation between oral and parenteral diphenhydramine therapy for treatment of opioid-induced pruritus in patients with sickle cell disease vaso-occlusive crisis (SCD VOC). Methods: This retrospective, single-center, cohort study included patients greater than or equal to 18 years old with sickle cell disease admitted for vaso-occlusive crisis who received either intravenous or oral diphenhydramine for opioid-induced pruritus. Patients were identified through ICD-9 and ICD-10 codes from June 1, 2016 through July 1, 2017. Rates of oversedation were compared between the 2 formulations. Secondary endpoints included length of stay, amount and duration of diphenhydramine, rate of acute chest and indication for IV therapy. Results: Fifty unique patients were included in the analysis representing 121 admissions. Seven patients received both formulations on separate admissions and were included in both groups. Twenty-nine percent of patients in the IV diphenhydramine group experienced oversedation (12/42) versus 13% in the oral diphenhydramine group (2/15, P = .312). The average number of admissions was significantly higher in the IV versus oral group (2.45 vs 1.20; P = .005) with average and median length of stay also significantly higher in the IV versus oral group (30.57, 16.0 vs 10.67, 10.0; P = .003). Conclusion: While there was no statistically significant difference in the rates of oversedation with use of IV versus oral diphenhydramine formulations, patients with SCD VOC who received IV diphenhydramine had more frequent admissions and a longer length of stay. Clinicians may consider oral diphenhydramine preferentially in appropriate patients over IV administration.

scholarly journals Variation in fetal hemoglobin parameters and predicted hemoglobin S polymerization in sickle cell children in the first two years of life: Parisian Prospective Study on Sickle Cell Disease

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3182-3188 ◽  
Author(s):  
M Maier-Redelsperger ◽  
CT Noguchi ◽  
M de Montalembert ◽  
GP Rodgers ◽  
AN Schechter ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Oxygen Saturation ◽  
Cell Population ◽  
Sickle Cell ◽  
Clinical Manifestations ◽  
Fetal Hemoglobin ◽  
Cell Disease ◽  
Normal Children ◽  
Hemoglobin S ◽  
F Cells

Abstract Intracellular hemoglobin S (HbS) polymerization is most likely to be the primary determinant of the clinical and biologic manifestations of sickle cell disease (SCD). Fetal hemoglobin (HbF) does not enter the HbS polymer and its intracellular expression in sickle erythrocytes inhibits polymerization. HbF levels, high at birth but decreasing thereafter, protect the newborn from the clinical manifestations of this hemoglobinopathy. We have measured the sequential changes in HbF, F reticulocytes, and F cells in the first 2 years of life in 25 children with SCD and compared the results with those obtained in 30 normal children (AA). We have also calculated HbF per F cell (F/F cell), the preferential survival of F cells versus non-F cells, as measured by the ratio F cells versus F reticulocytes (FC/FR) and polymer tendency at 40% and 70% oxygen saturation. HbF levels decreased from about 80.4% +/- 4.0% at birth to 9.2% +/- 2.9% at 24 months. During this time, we observed a regular decrease of the F reticulocytes and the F cells. The kinetics of the decline of F/F cell was comparable with the decline of HbF, rapid from birth (mean, 27.0 +/- 3.6 pg) to 12 months of age (mean, 8.5 +/- 1.5 pg) and then slower from 12 to 24 months of age (mean, 6.2 +/- 1.0 pg) in the SCD children. In the AA children, the decrease in HbF, due to changes in both numbers of F cells and F/F cell, was more precipitous, reaching steady-state levels by 10 months of age. Calculated values for mean polymer tendency in the F-cell population showed that polymerization should begin to occur at 40% oxygen saturation at about 3 months and increase progressively with age, whereas polymerization at 70% oxygen saturation would not occur until about 24 months. These values correspond to HbF levels of 50.8% +/- 10.8% and 9.2% +/- 2.9%, respectively, and F/F cell levels of 15.6 +/- 4.5 pg and 6.2 +/- 1.0 pg, respectively. In the non--F-cell population, polymerization was expected at birth at both oxygen saturation values. Three individuals had significantly greater predicted polymerization tendency than the remainder of the group because of early decreases in HbF. These individuals in particular, the remainder of the cohort, as well as other recruited newborns, will be studied prospectively to ascertain the relationship among hematologic parameters, which determine polymerization tendency and the various clinical manifestations of SCD.

Whole Blood Tissue Factor Procoagulant Activity Is Elevated in Patients With Sickle Cell Disease

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4216-4223 ◽  
Author(s):  
Nigel S. Key ◽  
Arne Slungaard ◽  
Luke Dandelet ◽  
Stephen C. Nelson ◽  
Christopher Moertel ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Tissue Factor ◽  
Mononuclear Cell ◽  
Sickle Cell ◽  
Whole Blood ◽  
Procoagulant Activity ◽  
Cell Disease ◽  
Blood Samples ◽  
Significant Difference ◽  
Whole Blood Samples

Abstract We developed a simple assay for the measurement of tissue factor procoagulant activity (TF PCA) in whole blood samples that avoids the need for mononuclear cell isolation. This method combines convenience of sample collection and processing with a high degree of sensitivity and specificity for TF. Using this method, we have determined that TF PCA is detectable in whole blood samples from normal individuals, which is itself a novel observation. Essentially all PCA could be shown to be localized in the mononuclear cell fraction of blood. Compared with controls, whole blood TF levels were significantly (P &lt; .000001) elevated in patients with sickle cell disease (SCD), regardless of the subtype of hemoglobinopathy (SS or SC disease). No significant difference in TF PCA was observed between patients in pain crisis compared with those in steady-state disease. Because TF functions as cofactor in the proteolytic conversion of FVII to FVIIa in vitro, it was expected that an increase in circulating TF PCA would lead to an increased in vivo generation of FVIIa. On the contrary, FVIIa levels were actually decreased in the plasma of patients with SCD. Plasma TF pathway inhibitor (TFPI) antigen levels were normal in SCD patients, suggesting that accelerated clearance of FVIIa by the TFPI pathway was not responsible for the reduced FVIIa levels. We propose that elevated levels of circulating TF PCA may play an important role in triggering the activation of coagulation known to occur in patients with SCD. Because TF is the principal cellular ligand for FVIIa, it is possible that increased binding to TF accounts for the diminished plasma FVIIa levels.

scholarly journals SP135RENAL INVOLVEMENT IN SICKLE CELL DISEASE IN TRIBAL WESTERN INDIA

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii422-iii422
Author(s):  
Mohan Patel ◽  
Vivek Kute ◽  
Praksh Ugale ◽  
Rajesh Valvi
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Western India ◽  
Cell Disease

Cell Free Fetal and Total DNA Levels in Pregnancies at Risk of Sickle Cell Disease and Significant Ethnic Variation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3791-3791
Author(s):  
Ageliki Gerovassili ◽  
Kypros H. Nicolaides ◽  
Swee Lay Thein ◽  
David Rees
Keyword(s):  
At Risk ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Globin Gene ◽  
Cell Disease ◽  
Maternal Weight ◽  
Chromosome 11 ◽  
Significant Difference ◽  
African Caribbean

Abstract Cell free (cf) DNA in maternal circulation is increasingly investigated in pregnancy. We aimed to determine if sickle cell trait women had quantitative differences of cfDNA with controls and if there was an ethnic difference between the cfDNA levels of Northern European and African/African-Caribbean populations. Non-invasive prenatal diagnosis through quantification of fetal and total cfDNA was tested in 33 pregnant women at risk of carrying a fetus affected with sickle cell disease and 124 control pregnancies. Fetal cfDNA assays were based on two Y chromosome specific markers (SRY and DYS14) and total cfDNA was based on the β-globin gene on chromosome 11. Maternal age (MA), gestation age (GA), fetal sex, storage time prior to extraction, maternal weight and body mass index (BMI) before pregnancy were compared to the fetal and total cfDNA levels. No significant difference in the fetal or total cfDNA levels was found between any of the control pregnancies and the sickle cell trait mothers carrying HbAA, HbAS and HbSS fetuses. However, higher levels of total cfDNA, but lower fetal cfDNA levels were observed in the African/African-Caribbean population compared with the Nothern Europeans. A significant variation in cfDNA was found between ethnic groups, which should be taken under consideration in future studies measuring cfDNA.

Sign in / Sign up

Export Citation Format

Share Document