Effects of chronic transfusions on abdominal sonographic abnormalities in children with sickle cell anemia.
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ABSTRACT:
SUBMITTER: McCarville MB
PROVIDER: S-EPMC3237893 | biostudies-literature | 2012 Feb
REPOSITORIES: biostudies-literature
Publications
Effects of chronic transfusions on abdominal sonographic abnormalities in children with sickle cell anemia.
McCarville Mary Beth MB Rogers Zora R ZR Sarnaik Sharada S Scott Paul P Aygun Banu B Hilliard Lee L Lee Margaret T MT Kalinyak Karen K Owen William W Garro Julian J Schultz William W Yovetich Nancy N Ware Russell E RE
The Journal of pediatrics 20110909 2
<h4>Objective</h4>To assess the effects of chronic erythrocyte transfusions on prevalence of sonographic incidence of organ damage in children with sickle cell anemia (SCA).<h4>Study design</h4>Children (N=148; mean age, 13.0 years) with SCA, receiving chronic transfusions (average, 7 years), underwent abdominal sonography at 25 institutions. After central imaging review, spleen, liver, and kidney measurements were compared with published normal values. Potential relations between ultrasound, cl ...[more]
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Project description:BACKGROUND:Blood transfusions are administered to children and adults with sickle cell anemia (SCA) for secondary stroke prevention, or as treatment for recurrent pain crises or acute anemia, but transfusion effects on cerebral hemodynamics and metabolism are not well-characterized. PURPOSE:To compare blood transfusion-induced changes in hemometabolic parameters, including oxygen extraction fraction (OEF) and cerebral blood flow (CBF), within and between adults and children with SCA. STUDY TYPE:Prospective, longitudinal study. SUBJECTS:Adults with SCA (n?=?16) receiving simple (n?=?7) or exchange (n?=?9) transfusions and children with SCA (n?=?11) receiving exchange transfusions were scanned once when hematocrit was near nadir and again within 7 days of transfusion. Adult controls without SCA or sickle trait (n?=?7) were scanned twice on separate days. FIELD STRENGTH/SEQUENCE:3.0T T1 -weighted, T2 -weighted, and T2 -relaxation-under-spin-tagging (TRUST) imaging, and phase contrast angiography. ASSESSMENT:Global OEF was computed as the relative difference between venous oxygenation (from TRUST) and arterial oxygenation (from pulse oximetry). Global CBF was computed as total blood flow to the brain normalized by intracranial tissue volume. STATISTICAL TESTS:Hemometabolic variables were compared using two-sided Wilcoxon signed-rank tests; associations were analyzed using two-sided Spearman's correlation testing. RESULTS:In adults with SCA, posttransfusion OEF?=?0.38?±?0.05 was lower (P?=?0.001) than pretransfusion OEF?=?0.45?±?0.09. A change in OEF was correlated with increases in hematocrit (P?=?0.02; rho?=?-0.62) and with pretransfusion hematocrit (P?=?0.02; rho?=?0.65). OEF changes after transfusion were greater (P?=?0.002) in adults receiving simple versus exchange transfusions. Posttransfusion CBF?=?77.7?±?26.4?ml/100g/min was not different (P?=?0.27) from pretransfusion CBF?=?82.3?±?30.2?ml/100g/min. In children with SCA, both posttransfusion OEF?=?0.28?±?0.04 and CBF?=?76.4?±?26.4 were lower than pretransfusion OEF?=?0.36?±?0.06 (P?=?0.004) and CBF?=?96.4?±?16.5 (P?=?0.004). DATA CONCLUSION:Cerebral OEF reduces following transfusions in adults and children with SCA. CBF reduces following transfusions more often in children compared to adults, indicating that vascular reserve capacity may remain near exhaustion posttransfusion in many adults. LEVEL OF EVIDENCE:2 Technical Efficacy Stage 5 J. Magn. Reson. Imaging 2019;49:466-477.
| S-EPMC6330124 | biostudies-literature
Project description:BackgroundSilent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care.MethodsIn this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct.ResultsA total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04).ConclusionsRegular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.).
| S-EPMC4195437 | biostudies-literature
Project description:Stroke is one of the most disabling complications of sickle cell anemia (SCA). The molecular mechanisms leading to stroke in SCA or by which packed red blood cell (PRBC) transfusion prevents strokes are not understood. We investigated the effects of PRBC transfusion on serum biomarkers in children with SCA who were at high-risk for stroke. Serum samples from 80 subjects were analyzed, including baseline, study exit time point and 1 year after study exit. Forty of the 80 samples were from subjects randomized to standard care and 40 from transfusion arm. Samples were assayed for levels of BDNF, sVCAM-1, sICAM-1, MPO, Cathepsin-D, PDGF-AA, PDGF-AB/BB, RANTES (CCL5), tPAI-1, and NCAM-1 using antibody immobilized bead assay. Significantly lower mean serum levels of sVCAM-1 (2.2 × 10(6) ± 0.8 × 10(6) pg/mL vs. 3.1 × 10(6) ± 0.9 × 10(6) pg/mL, P < 0.0001), Cathepsin-D (0.5 × 10(6) ± 0.1 × 10(6) pg/mL vs. 0.7 × 10(6) ± 0.2 × 10(6) pg/mL, P < 0.0001), PDGF-AA (10556 ± 4033 pg/mL vs. 14173 ± 4631 pg/mL, P = 0.0008), RANTES (0.1 × 10(6) ± 0.07 × 10(6) pg/mL vs. 0.2 × 10(6) ± 0.06 × 10(6) pg/mL, P < 0.006), and NCAM-1 (0.7 × 10(6) ± 0.2 × 10(6) pg/mL vs. 0.8 × 10(6) ± 0.1 × 10(6) pg/mL, P < 0.0006) were observed among participants who received PRBC transfusion, compared to those who received standard care. Twenty or more PRBC transfusion over 4 years was associated with lower serum levels of sVCAM-1 (P < 0.001), PDGF-AA (P = 0.025), and RANTES (P = 0.048). Low baseline level of BDNF (P = 0.025), sVCAM-1 (P = 0.025), PDGF-AA (P = 0.01), t-PAI-1 (P = 0.025) and sICAM-1 (P = 0.022) was associated with higher probability of stroke free survival. Beyond improving hemoglobin levels, our results suggest that the protective effects of PRBC transfusion on reducing stroke in SCD may result from reduced thrombogenesis and vascular remodeling.
| S-EPMC4070426 | biostudies-literature
Project description:ObjectiveThis study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA).MethodsParticipants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group. We hypothesized that individuals with SCA would exhibit reductions in frontal lobe cortex thickness and reduced basal ganglia and thalamus volumes compared with HCs and that these structural brain abnormalities would be associated with measures of cognitive functioning (Wechsler Adult Intelligence Scale, 3rd edition).ResultsAfter adjusting for age, sex, education level, and intracranial volume, participants with SCA exhibited thinner frontal lobe cortex (t = -2.99, p = 0.003) and reduced basal ganglia and thalamus volumes compared with HCs (t = -3.95, p < 0.001). Reduced volume of the basal ganglia and thalamus was significantly associated with lower Performance IQ (model estimate = 3.75, p = 0.004) as well as lower Perceptual Organization (model estimate = 1.44, p = 0.007) and Working Memory scores (model estimate = 1.37, p = 0.015). Frontal lobe cortex thickness was not significantly associated with any cognitive measures.ConclusionsOur findings suggest that basal ganglia and thalamus abnormalities may represent a particularly salient contributor to cognitive dysfunction in adults with SCA.
| S-EPMC3959758 | biostudies-literature
Project description:Blood transfusions are the mainstay of stroke prevention in pediatric sickle cell anemia (SCA), but the physiology conferring this benefit is unclear. Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) are elevated in SCA, likely compensating for reduced arterial oxygen content (CaO2). We hypothesized that exchange transfusions would decrease CBF and OEF by increasing CaO2, thereby relieving cerebral oxygen metabolic stress. Twenty-one children with SCA receiving chronic transfusion therapy (CTT) underwent magnetic resonance imaging before and after exchange transfusions. Arterial spin labeling and asymmetric spin echo sequences measured CBF and OEF, respectively, which were compared pre- and posttransfusion. Volumes of tissue with OEF above successive thresholds (36%, 38%, and 40%), as a metric of regional metabolic stress, were compared pre- and posttransfusion. Transfusions increased hemoglobin (Hb; from 9.1 to 10.3 g/dL; P < .001) and decreased Hb S (from 39.7% to 24.3%; P < .001). Transfusions reduced CBF (from 88 to 82.4 mL/100 g per minute; P = .004) and OEF (from 34.4% to 31.2%; P < .001). At all thresholds, transfusions reduced the volume of peak OEF found in the deep white matter, a location at high infarct risk in SCA (P < .001). Reduction of elevated CBF and OEF, both globally and regionally, suggests that CTT mitigates infarct risk in pediatric SCA by relieving cerebral metabolic stress at patient- and tissue-specific levels.
| S-EPMC5833262 | biostudies-literature
Project description:BackgroundThe high prevalence of airway hyperresponsiveness (AHR) among children with sickle cell anemia (SCA) remains unexplained.MethodsTo determine the relationship between AHR, features of asthma, and clinical characteristics of SCA, we conducted a multicenter, prospective cohort study of children with SCA. Dose response slope (DRS) was calculated to describe methacholine responsiveness, because 30% of participants did not achieve a 20% decrease in FEV1 after inhalation of the highest methacholine concentration, 25 mg/mL. Multiple linear regression analysis was done to identify independent predictors of DRS.ResultsMethacholine challenge was performed in 99 children with SCA aged 5.6 to 19.9 years (median, 12.8 years). Fifty-four (55%) children had a provocative concentration of methacholine producing a 20% decrease in FEV1<4 mg/mL. In a multivariate analysis, independent associations were found between increased methacholine responsiveness and age (P<.001), IgE (P=.009), and lactate dehydrogenase (LDH) levels (P=.005). There was no association between methacholine responsiveness and a parent report of a doctor diagnosis of asthma (P=.986). Other characteristics of asthma were not associated with methacholine responsiveness, including positive skin tests to aeroallergens, exhaled nitric oxide, peripheral blood eosinophil count, and pulmonary function measures indicating airflow obstruction.ConclusionsIn children with SCA, AHR to methacholine is prevalent. Younger age, serum IgE concentration, and LDH level, a marker of hemolysis, are associated with AHR. With the exception of serum IgE, no signs or symptoms of an allergic diathesis are associated with AHR. Although the relationship between methacholine responsiveness and LDH suggests that factors related to SCA may contribute to AHR, these results will need to be validated in future studies.
| S-EPMC3047289 | biostudies-literature
Project description:Children with sickle cell anemia (SCA) are at increased risk for invasive pneumococcal disease; antibiotic prophylaxis significantly reduces this risk. We calculated the proportion of children with SCA who received ≥300 days of antibiotic prophylaxis and identified predictors of such receipt. Children aged 3 months to 5 years with SCA were identified by the presence of 3 or more Medicaid claims with a diagnosis of SCA within a calendar year (2005-2012) in Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. Receipt of antibiotics was identified through claims for filled prescriptions. The outcome, receipt of ≥300 days of antibiotics, was assessed annually by using varying classifications of antibiotics. By using logistic regression with generalized estimating equations, we estimated the odds of receiving ≥300 days of antibiotics, with potential predictors of age, sex, year, state, and health services use. A total of 2821 children contributed 5014 person-years. Overall, only 18% of children received ≥300 days of antibiotics. Each additional sickle cell disease-related outpatient visit (odds ratio = 1.01, 95% confidence interval: 1.01-1.02) and well-child visit (odds ratio = 1.08, 95% confidence interval: 1.02-1.13) was associated with incrementally increased odds of receiving ≥300 days of antibiotics. Despite national recommendations and proven lifesaving benefit, antibiotic prophylaxis rates are low among children with SCA. Numerous health care encounters may offer an opportunity for intervention; in addition, such interventions likely need to include social factors that may affect the ability for a child to receive and adhere to antibiotic prophylaxis.
| S-EPMC7252515 | biostudies-literature
Project description:Sickle cell anemia (SCA) is an inherited blood disorder that affects over 300,000 newborns worldwide every year, being particularly prevalent in Sub-Saharan Africa. Despite being a monogenic disease, SCA shows a remarkably high clinical heterogeneity. Several studies have already demonstrated the existence of some polymorphisms that can provide major clinical benefits, producing a mild phenotype. Moreover, the existence of distinct haplotypes can also influence the phenotype patterns of certain populations, leading to different clinical manifestations. Our aim was to assess the association between polymorphisms in genes previously related to SCA disease severity in an Angolan pediatric population. This study analyzed clinical and biological data collected from 192 Angolan children. Using NGS data, we classified the HBB haplotypes based on four previously described SNPs (rs3834466, rs28440105, rs10128556, and rs968857) and the genotype for the SNPs in HBG2 (rs7482144), BCL11A (rs4671393, rs11886868, rs1427407, rs7557939), HBS1L-MYB (rs66650371) and BGLT3 (rs7924684) genes. The CAR haplotype was undoubtedly the most common HBB haplotype in our population. The HbF values and the ratio of gamma chains were statistically significant for almost all of the variants studied. We reported for the first time an association between rs7924684 in the BGLT3 gene and gamma chains ratio. The current findings emphasize the importance personalized medicine would have if applied to SCA patient care, since some of the variants studied might predict the phenotype and the overall response to treatment.
| S-EPMC8158763 | biostudies-literature
Project description:Background and objectiveSusceptibility to encapsulated bacteria is well known in sickle cell disease (SCD). Hydroxyurea use is common in adults and children with SCD, but little is known about hydroxyurea's effects on immune function in SCD. Because hydroxyurea inhibits ribonucleotide reductase, causing cell cycle arrest at the G1-S interface, we postulated that hydroxyurea might delay transition from naive to memory T cells, with inhibition of immunologic maturation and vaccine responses.MethodsT-cell subsets, naive and memory T cells, and antibody responses to pneumococcal and measles, mumps, and rubella vaccines were measured among participants in a multicenter, randomized, double-blind, placebo-controlled trial of hydroxyurea in infants and young children with SCD (BABY HUG).ResultsCompared with placebo, hydroxyurea treatment resulted in significantly lower total lymphocyte, CD4, and memory T-cell counts; however, these numbers were still within the range of historical healthy controls. Antibody responses to pneumococcal vaccination were not affected, but a delay in achieving protective measles antibody levels occurred in the hydroxyurea group. Antibody levels to measles, mumps, and rubella showed no differences between groups at exit, indicating that effective immunization can be achieved despite hydroxyurea use.ConclusionsHydroxyurea does not appear to have significant deleterious effects on the immune function of infants and children with SCD. Additional assessments of lymphocyte parameters of hydroxyurea-treated children may be warranted. No changes in current immunization schedules are recommended; however, for endemic disease or epidemics, adherence to accelerated immunization schedules for the measles, mumps, and rubella vaccine should be reinforced.
| S-EPMC4179098 | biostudies-literature
Project description:Whole transcriptome RNA-sequencing was performed to quantify RNA expression changes in whole blood samples collected from steady state sickle cell anemia (SCA) and control subjects. Pediatric SCA and control subjects were recruited from Atlanta (GA)-based hospital(s) systems and consented for RNA sequencing. RNA sequencing was performed on an Ion Torrent S5 sequencer, using the Ion Total RNA-seq v2 protocol. Data were aligned to the hg19 reference genome and analyzed in the Partek Genomics studio package (v7.0). 223 genes were differentially expressed between SCA and controls (± 1.5 fold change FDR p < 0.001) and 441 genes show differential transcript expression (± 1.5 fold FDR p < 0.001). Differentially expressed RNA are enriched for hemoglobin associated genes and ubiquitin-proteasome pathway genes. Further analysis shows higher gamma globin gene expression in SCA (33-fold HBG1 and 49-fold HBG2, both FDR p < 0.05), which did not correlate with hemoglobin F protein levels. eQTL analysis identified SNPs in novel non-coding RNA RYR2 gene as having a potential regulatory role in HBG1 and HBG2 expression levels. Gene expression correlation identified JHDM1D-AS1(KDM7A-DT), a non-coding RNA associated with angiogenesis, enhanced GATA1 and decreased JAK-STAT signaling to correlate with HBG1 and HBG2 mRNA levels. These data suggest novel regulatory mechanisms for fetal hemoglobin regulation, which may offer innovative therapeutic approaches for SCA.
| S-EPMC8793691 | biostudies-literature