Implementation of a European Cohort to Follow Sickle Cell Children and Adults Treated with Hydroxycarbamide

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 564-564
Author(s):  
Mariane De Montalembert ◽  
Frédéric Galacteros ◽  
Jean Antoine Ribeil ◽  
Uwe Kordes ◽  
Jean Benoit Arlet ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Safety Profile ◽  
Conflicts Of Interest ◽  
Subcutaneous Tissue ◽  
Acute Chest Syndrome ◽  
Control Group ◽  
Cell Disease ◽  
Skin Reactions ◽  
Number Of Patients

Abstract Hydroxycarbamide (HU) is a myelosuppressive drug marketed since 1968 for the treatment of hematological cancer, and authorized since 2007 in Europe as orphan medicinal product for the prevention of recurrent vaso-occlusive crises including acute chest syndrome in adults and children older than 2 years with sickle cell disease (SCD). ESCORT-HU (European Sickle Cell Disease Cohort – Hydroxyurea) is a multicenter prospective non interventional study implemented in Europe to collect more information about the safety profile of HU and morbi-mortality in SCD patients treated with HU. The study responds to EMA (European Medicines Agency) request and has been approved by the Ethical of Necker Enfants Malades Hospital (Paris, France).The ongoing study involves the largest number so far of patients with SCD treated with HU. Primary endpoints of ESCORT HU are to determine frequency of adverse events, and possible consequent changes of HU treatment. Secondary endpoints are to evaluate morbi-mortality of the disease although in the absence of control group. From June 2008 to June 2014, 483 patients (255 females; 228 males) were enrolled from 3 European countries, Greece (24%), Germany (19%), and France (56%). 67% patients were adults, median aged 37.35 yrs (17-83.5) and 33% were children, median aged 11.06 yrs (2.6-16.9). genotypes were HbS/HbS in 71.4% cases, and compound heterozygotous HbS/β-thalassemia in 22.8 % (Table 1). 137 (28.4%) patients experienced 421 events (Table 2). 132 (32.2%) of these events may be attributed to HU. The safety profile is roughly similar in children and adults. As expected the most frequent side effects were firstly blood disorders (n=86 events, 42.4%) such as neutropenia or thrombocytopenia. In all cases, these cytopenias were rapidly resolved with the transitory stop of HU. 71 events related to skin and subcutaneous tissue disorders were observed, mostly cutaneous dryness, skin reactions, alopecia and nails or skin pigmentation; 4 patients had a leg ulcer (34.8%). Most of these events are ongoing or stabilized despit the decrease of HU. No secondary cancer has been reported until now. Even if HU is an old drug with a relatively well-known safety profile, some uncertainties remain in terms of long-term safety as well as tolerance in the youngest people. The main interest of ESCORT HU is to offer the possibility of safety surveillance of hydroxycarbamide in European sickle cell patients. Table 1 Demographic data Adults Children < 17 years old Total Number of patients 322 (67%) 161 (33%) 483 Females/Males 183/139 72/89 255/228 Median age (yrs) (range) 37.35 (17-83.5) 11.06 (2.6-16.9) 28.58 Genotype SS 206 (64%) 139 (86.3%) 345 (71.4%) SC 1 (0.3%) 3 (1.86%) 4 (0.8%) Sβ0 51 (15.8%) 11 (6.8%) 62 (12.8%) Sβ+ 46 (14.2%) 2 (1.2%) 48 (9.9%) Other 18 (5.5%) 6 (3.7%) 24 (4.9%) Treatment with HU before enrollment in ESCORT HU No of pts 232 83 315 (65%) Median duration (range) of HU treatment before ESCORT HU 8.2 yrs (0.5 ans-24 yrs) 3. 1 yrs ( 71 days – 8.9 yrs) 6.85 (71 days-24 years)] HU ESCORT Daily mean dose (mg/kg/d) 16.11 ± 4.79 19.63 ± 4.69 17.32 ± 4.94 Abstract 564. Table 2 The most frequent events of hydroxycarbamide in the two populations of SCD patients ADULTS CHILDREN No ofGerman(%) No of adults No ofEpisodes(%) No of children Total(% /411) Events Related to HU treatment (Siklos®)(%**) Blood and lymphatic system disorders (%) 32 (17.7) 22 54 (31.03) 28 86 (20.9) 56 (65.1) Skin and subcutaneous tissue disorders (%) 42 (23.2) 28 29 (16.7) 19 71 (17.3) 46 (64.8) Nervous system disorders Headache (24), Dizziness/vertigo (14), 32 (17.7) 23 12(6.9) 10 44 (10.7) 11 (25) Gastrointestinal disorders Nausea (14), diarrhea (8), other (14) 20 (11) 17 23 (13.2) 16 43 (10.4) 7 (16.3) Metabolic and nutrition disorders: vit D deficiency (17), weight gain (5) 13 (7) 11 18 (18.3) 18 36 (8.75) 4 (11.1) Fever 11 (6) 10 12(6.9) 7 23 (5.6) 1 (4.3) Cardiac disorders (hypertension, bradycardia, chest pain, cardiomegaly) 4 4 2 2 6 1 (16.6) General disorders : fatigue 5 5 0 0 5 0 Hepatobiliary disorders 2 2 0 0 2 0 Neoplasms benign, malignant and unspecified (incl. cysts and polyps) Harmatoma, benign vulvar sebaceous cyst 2 2 0 0 2 0 Renal & urinary disorders 2 2 0 0 2 0 Reproductive system and breast disorders 3 3 0 0 3 0 Other 13 13 21 14 34 6 (17.1%) 181 80 /181(24.8%) 174 57 / 174(35.4%) 411 132/411 (32.2%) ** compared to the total number of “system organ class” events Disclosures No relevant conflicts of interest to declare.

scholarly journals Complications in Pregnancy of Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-33
Author(s):  
Avani Singh ◽  
Conner Olsen ◽  
Xu Zhang ◽  
Robert E. Molokie
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Mode Of Delivery ◽  
Acute Chest Syndrome ◽  
Control Group ◽  
Thromboembolic Events ◽  
Cell Disease ◽  
Fetal Outcomes ◽  
Systemic Complications

Sickle cell disease (SCD) has many systemic complications including vaso-occlusive crises (VOC), stroke and increased mortality. However, as a result of advances in the care of children with SCD, over 90% of those born with SCD in the US live until they are at least 20 years of age. As survival improves, more women with SCD are able to have children. Through improvements in the management of pregnancy, the majority of women with SCD can have an uncomplicated birth though they do have a high incidence of medical and pregnancy complications compared to those women with normal phenotype. While current literature regarding pregnancy in SCD often compares sickle cell patients to normal hemoglobin phenotype patients, more research is needed comparing individuals with SCD. This study seeks to examine the number of vaso-occlusive crises, acute chest syndrome (ACS) episodes and thromboembolic events in pregnant patients with SCD, comparing during pregnancy, the 12 months before and the 12 months after pregnancy. A 10-year retrospective study was conducted at University of Illinois Health System (UIH) and included women over the age of 18 with sickle cell disease and pregnancy. These patients followed primarily at UIH for both their sickle cell and obstetric care. The query included 208 pregnancies and 177 patients. The primary endpoint was to compare the number of VOC, ACS, and thromboembolic events in patients with sickle cell disease during 9 months of pregnancy, the 12 months prior to their pregnancy and the 12 months after their pregnancy. Secondary endpoints include prophylactic, simple, and exchange transfusions throughout the pregnancy, mode of delivery, obstetric complications (preeclampsia, eclampsia, mortality), and fetal complications (IUGR, Apgar scores, mortality). Of 208 pregnancies from the initial query, 121 met inclusion criteria for the study. 87 of the 208 pregnancies met exclusion criteria due to other hemoglobin genotypes, delivery outside the study timeframe, delivery at outside hospital, or encounters for ectopic pregnancies, spontaneous or elective abortions. Paired comparisons between pregnancy, 12 months before the pregnancy, and 12 months after the pregnancy were carried out using non-parametric method (Wilcoxon's test) or generalized mixed effects models. Results demonstrated a statistically significant increase in VOC and ACS during pregnancy, compared to the 12 months prior and 12 months after pregnancy, as demonstrated in Table 2. Thromboembolic events had a slight trend of increase during pregnancy compared to the period before or after. These results were adjusted for age at delivery and restricted to SS genotype. VOC and severe genotype were found to associate with maternal and fetal outcomes such as C-section (p=0.04), transfusion requirement at delivery (p=0.007), low birth weight (p=0.008), and preterm delivery (p=0.02). Our findings demonstrate a definitive and statistically significant increase in VOC and ACS during pregnancy compared to the 12 months before or after pregnancy among women with SCD. This unique study compares patients with SCD to themselves longitudinally through time, utilizing a superior control group. Although this increase in VOC and ACS has been observed previously, prior studies compared pregnant patients with SCD to other patients with SCD, or to controls with normal hemoglobin. As hypothesized, thromboembolic events had a slight trend towards increasing during pregnancy, however this comparison was not statistically significant. Although prior data has shown prophylactic transfusions to decrease VOC in pregnant women with SCD, prophylactic transfusions were rarely utilized in this study group. These results demonstrate a definitive increase in VOC in pregnant individuals with SCD, and additionally affecting maternal and neonatal outcomes. Based on this study, decreasing rates of VOC during pregnancy may improve maternal and fetal outcomes. This may be achieved with prophylactic transfusions; however additional studies must be conducted to improve care in this patient population. This study will also allow us to further investigate additional characteristics that change during this timeline during pregnancy. This offers new opportunities to institute individualized preventive strategies, expanding the role of personalized medicine in the care of sickle cell patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Case Report: Acute Stroke in Young Adult Patient with Moyamoya Syndrome Secondary to Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Oladipo Cole ◽  
Asia Filatov ◽  
Javed Khanni ◽  
Patricio Espinosa
Keyword(s):  
Case Report ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Moyamoya Disease ◽  
Conflicts Of Interest ◽  
Acute Chest Syndrome ◽  
African American Female ◽  
Moyamoya Syndrome ◽  
Cell Disease ◽  
Radiographic Findings

Moyamoya disease, well described in literature, is a chronic cerebrovascular occlusive disorder. It is characterized by progressive stenosis/occlusion of the terminal portions of the internal carotid arteries (ICA) and the proximal portions of the middle cerebral arteries (MCA). Less frequently described is Moyamoya syndrome, the name given to radiographic findings consistent with Moyamoya disease, but with an identifiable cause. The diseases associated with Moyamoya Syndrome include Sickle Cell Disease (SCD), Thalassemias, and Down's Syndrome to name a few. Common complications of Moyamoya include both ischemic and hemorrhagic strokes. Upon literature review, Moyamoya syndrome caused by SCD is not well described. When it is, the discussion is centered around the pediatric patient population and surgical management. Our case report describes a 22-year-old African American female with SCD who initially presented with Acute Chest Syndrome. Her hospital course was complicated by development of overt debilitating neurologic deficits. Subsequently, she was found to have Moyamoya Syndrome on neuroimaging. She was successfully treated with medical management without any surgical intervention. This case highlights the necessity of thorough examination, differential diagnosis, imaging findings, and consideration of predisposing syndromes in the work-up for Moyamoya syndrome; especially individuals with Sickle Cell Disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Utility of Procalcitonin in Differentiating Acute Chest Syndrome from Vaso-Occlusive Crisis in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Satish Maharaj ◽  
Simone Chang ◽  
Karan Seegobin ◽  
Marwan Shaikh ◽  
Kamila I. Cisak
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Complete Blood Count ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Acute Chest Syndrome ◽  
Adult Males ◽  
Cell Disease ◽  
Unequal Variances ◽  
Recorded Data

Background: Acute chest syndrome (ACS) frequently complicates sickle cell disease (SCD) and is a leading cause of hospitalization and mortality. Many factors have been implicated in ACS, including infections, thrombosis, fat and pulmonary emboli. However, a clear etiology is not defined in 50% of the cases and ACS is considered a clinical endpoint for different pathogenic processes (Vichinsky et al 2000). The non-specific nature of ACS makes diagnostic tests challenging, and there are no serum tests clinical used to aid diagnosis. Procalcitonin (PCT) is a prohormone of calcitonin and serum PCT rises within hours of an inflammatory stimulus. PCT has clinical utility as a marker of severe systemic inflammation, infection, and sepsis (Becker et al. 2008). Few studies have evaluated PCT as a biomarker for ACS in patients presenting with vaso-occlusive crises (VOC). Two studies have reported no difference in PCT (Biemond et al. 2018 and Stankovic et al 2011), while one study reported higher PCT between ACS and VOC (Patel et al 2014). Methods: We retrospectively reviewed 106 patients with SCD who presented to the emergency department with fever and painful crises during 2015-2019. The patients were divided into two categories based on discharge diagnoses - patients with VOC only (n=88) and patients with ACS (n=18). Inclusion criteria for both groups were patients with SCD, 17 years and older and PCT measurement on presentation. Exclusion criteria were defined as patients who had received empiric antibiotics prior to PCT testing. Data collected on presentation included genotype, age, gender, complete blood count, PCT, creatinine, total bilirubin and hydroxyurea use. Length of stay was recorded. Data was analyzed between the two groups using descriptive statistics and accounting for unequal variances, withp-value set at 0.05 for significance. Results: Demographics and clinical characteristics are summarized in Table 1 (Figure). The sample included primarily adult males (77%), with about two-thirds on hydroxyurea. Genotype HbSS (73.6%) was most prevalent followed by HbSC (22.6%) and HbSβ (3.8%). The ACS group had a higher percentage of HbSS, lower use of hydroxyurea and higher mean bilirubin. Mean PCT for the ACS group was 0.52 ng/mL (range, 0.05-2.04), compared to 0.31 ng/mL (range, 0.02-6.82) in the VOC group; withp=0.084. ROC analysis showed a PCT&gt;0.5ng/mL had 39% sensitivity and 85% specificity for ACS in this sample. Conclusion: In this sample, PCT on presentation was higher in those with ACS compared to VOC, but this difference did not achieve statistical significance. Further study in a larger population would be useful to evaluate this finding. Disclosures No relevant conflicts of interest to declare.

Polymorphisms in TNFα Are Associated with Cerebrovascular Events in Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1540-1540 ◽  
Author(s):  
Latorya A Barber ◽  
Allison E Ashley-Koch ◽  
Melanie E. Garrett ◽  
Karen L Soldano ◽  
Marilyn J. Telen
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Umbilical Vein ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Data Set ◽  
Clinical Complications ◽  
Cerebrovascular Events ◽  
Increased Risk

Abstract Abstract 1540 Poster Board I-563 Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine that stimulates phagocytosis, neutrophil recruitment, and expression of adhesion molecule VCAM-1. Plasma levels of TNFα have been found to be increased in sickle cell disease (SCD), and in vitro studies show that TNFα causes increased adherence of sickle red blood cells to human umbilical vein endothelial cells. A polymorphism in the promoter region of the TNFα gene has previously been associated with stroke in children with SCD (Hoppe et al., 2007). The current study was designed to identify associations of additional TNFα single nucleotide polymorphisms (SNPs) with SCD clinical complications. We analyzed five SNPs in the TNFα gene in 509 DNA samples of SCD patients from Duke University, University of North Carolina at Chapel Hill, and Emory University. In our data set, cerebrovascular events (CVEs), including overt stroke, seizures, and transient ischemic attacks, occurred in 133 out of 509 SCD patients (26.1%). SNP genotyping was performed using Taqman genotyping assays from Applied Biosystems. Due to low minor allele frequencies (<0.05) for all the SNPs examined, genetic associations with SCD clinical complications were examined by using allele tests. After controlling for age, gender, and use of hydroxyurea, two of the five TNFα SNPs, rs2228088 and rs3093665, were significantly associated with CVEs (p=0.013 and 0.029, respectively). The odds that SCD patients with a G allele at rs2228088 suffered from CVEs were 0.485 times that for patients with the T allele, suggesting that the G allele had a protective effect. The odds of having the A allele at rs3093665 and suffering from CVEs was also reduced, at 0.45 compared to the C allele. Neither SNP was found to be in linkage disequilibrium (LD) with any of the other SNPs analyzed (r2≤0.002). There was also strong association of SNP rs2228088 with acute chest syndrome (ACS; p=0.003), occurring in 382 out of 509 SCD patients (75%). However, in this analysis, the G allele was associated with increased risk for ACS (OR=2.313). In addition to the association with CVEs, the SNP rs3093665 was also significantly associated with priapism (p=0.03), reported by 86 of 223 male SCD patients (38.6%). In this analysis, the A allele was protective, as had been observed for CVE (OR=0.188). Additionally, we found no difference in steady state plasma TNFα levels between genotypes for the two SNPs. The functional significance of these SNPs is presently unknown. SNP rs2228088 is a synonymous SNP located in the coding region, and rs3093665 is located in the 3' untranslated region of the TNFα gene. While the G to T change at SNP rs2228088 does not translate to a change in amino acid sequence, the A to C change at SNP rs3093665 may affect mRNA stability due to its location. It is also possible that one or both of these SNPs is in LD with another functionally relevant SNP. Our findings thus support previous data implicating TNFα polymorphisms in risk for central nervous system events. Interestingly, ACS has been previously associated with seizures, stroke and altered mental status in adults and children with SCD (Vinchinsky et al., 2000) and with silent cerebral infarcts and reversible posterior leukoencephalopathy syndrome in children with SCD (Henderson et al., 2003). However, in our dataset, ACS and the occurrence of CVEs were not associated (p=0.24). Further studies are required to elucidate these and other factors that potentially correlate with SCD clinical complications. Disclosures No relevant conflicts of interest to declare.

Microparticles As Biomarkers Of Osteonecrosis Of The Hip In Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2226-2226
Author(s):  
Anne M Marsh ◽  
Raymond Schiffelers ◽  
Ginny Gildengorin ◽  
Frans A Kuypers ◽  
Carolyn Hoppe
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Vascular Occlusion ◽  
Predictive Biomarker ◽  
Acute Chest Syndrome ◽  
Mobility Limitations ◽  
Cell Disease ◽  
The Past ◽  
D Dimer

Abstract Introduction Sickle cell disease (SCD) is the most common cause of osteonecrosis of the femoral head (ONFH) in children. ONFH is a debilitating condition that is associated with mobility limitations, chronic pain, and an impaired quality of life. While the mechanisms that cause ONFH remain unknown, ischemia from recurrent microvascular occlusion is likely to play a role. Vascular occlusion may result directly from obstruction by sickled cells, or indirectly via complex interdependent pathways characterized by sustained endothelial activation, chronic inflammation, and coagulation. Microparticles (MP) are small, cell membrane-derived vesicles generated in response to cellular activation, injury or apoptosis. MPs have emerged as potential modulators of inflammation and thrombosis and have been found to be elevated in patients with ONFH in the general population. Objective This pilot study examined whether microparticle levels in patients with SCD who have ONFH differ from SCD patients without ONFH, as well as healthy African American (AA) controls. Methods Subjects were recruited at their baseline status and were excluded if they had been transfused within the past 30 days, hospitalized for a vaso-occlusive pain episode, acute chest syndrome, fever or surgery within the past 30 days, or had bony lesions of the femur or hip due to causes unrelated to SCD. For MP analysis, whole blood was collected in sodium citrate tubes and centrifuged for 15 minutes at 1500 x g at 20° C to generate platelet poor plasma. Aliquots of the plasma were immediately frozen and stored at -80° C until the time of MP analysis. 300 μl samples were diluted in PBS and centrifuged at 10000 x g for 1hr and the supernatant was centrifuged at 100,000 x g for 2 hr. The pellet was re-suspended in 1 mL of PBS and subjected to nanoparticle-tracking analysis to determine concentration and size. Additional laboratory biomarkers of inflammation and coagulation, including highly-sensitive C-reactive protein (hs-CRP), von Willebrand factor antigen (vWF Ag), tissue factor (TF), and D-dimer were analyzed for differences between groups. Analysis of variance was used to compare MP and biomarker levels between the three groups. The institutional review board at Children's Hospital & Research Center Oakland approved the study protocol and written informed consent was obtained from all participants. Results Characteristics of the 30 subjects enrolled are shown in Table I. Total microparticle levels in ONFH(+) patients were 2.3-fold higher than in ONFH(-) patients, and 2.5-fold higher than in AA controls (Figure 1). Mean MP levels for ONFH(+) patients, ONFH(-) patients, and AA controls were 4.55 x 1010, 1.99 x 1010, and 1.85 x 1010, respectively. Microparticle levels in ONFH(-) SCD patients did not differ from AA controls. There were no statistically significant differences in hsCRP, vWF Ag, TF, or D-dimer levels between the ONFH(-) and ONFH(+) groups. Conclusions The results of this study demonstrate significantly elevated MP levels in individuals with SCD who have ONFH. Additional studies are needed to better understand the mechanistic effects of MPs on the development of ONFH and to determine whether MP levels may be useful as a predictive biomarker for early disease detection. This publication was supported by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Risk Factors Predisposing Development of Priapism in Sickle Cell Disease Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4917-4917
Author(s):  
Salam Alkindi ◽  
Said AlMufargi ◽  
Anil Pathare
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Cardiovascular Response ◽  
Acute Chest Syndrome ◽  
Serum Total Bilirubin ◽  
Cell Disease ◽  
Retrospective Case ◽  
Chi Square ◽  
Sexual Stimulation

Abstract Background and Purpose: Penile erection and detumescence are complex physiologic processes, which require delicate neurohormonal and cardiovascular response. Priapism is defined as a persistent and painful erection lasting longer than four hours without sexual stimulation. Stuttering priapism is characterized by a self-limited, recurrent, and intermittent erection, frequently occurring in patients with sickle cell disease(SCD). The aim of this study was to identify the clinical and laboratory features in SCD patients with priapism in Oman. Methodology: In this retrospective case-control study, medical records of all patients with SCD who developed priapism were retrieved from the hospital information system and compared in a 1: 1 ratio with age and gender matched SCD patients who did not ever had priapism. Addition information extracted include hematological and laboratory parameters, treatment, and complications. Data obtained were analyzed using IBM SPSS version 23. The study was conducted following approval from the hospital medical research and ethics committee. Results & Discussion: Amongst the forty-one SCD patients evaluated, in the 21 patients with priapism (mean age 24.7 yrs), there was a significantly higher WBC, platelet, retic counts, LDH and serum total bilirubin as compared to controls (p<0.05, student's t test). However, there was no significant differences in the incidence of vaso-occlusive crisis, acute chest syndrome, pulmonary hypertension or cerebrovascular accident (p >0.05, Chi Square test). Patients with priapism were managed with exchange transfusion (100%), aspiration (52%) and shunting (5%). Interestingly, none of these patients showed impotence, although 10% manifested with infertility. Conclusions: Priapism in this SCD cohort is a disease of the young, and seen predominantly in the hemolytic phenotype of the disease. Patients with priapism showed high WBC's, Platelets, Bilirubin, LDH and retics with a lower hemoglobin as compared to the controls. Favorable outcome is dependent on early intervention and almost half of these patients needed surgical intervention. Disclosures No relevant conflicts of interest to declare.

Leukocyte Apoptosis and Inflammation in Iron-Overloaded Patients with Sickle Cell Disease or β-Thalassemia: A Mechanism for Increased Stroke and Disease Severity in Sickle Cell Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1233-1233 ◽  
Author(s):  
Patrick B. Walter ◽  
David W. Killilea ◽  
Ellen B. Fung ◽  
Annie Lui ◽  
Jacqueline Madden ◽  
...  
Keyword(s):  
Cell Death ◽  
Sickle Cell Disease ◽  
Disease Severity ◽  
Sickle Cell ◽  
Strong Predictor ◽  
Acute Chest Syndrome ◽  
Control Group ◽  
Cell Disease ◽  
Delayed Cell Death ◽  
Leukocyte Number

Abstract Sickle cell disease (SCD) is a hemoglobinopathy characterized by micro-vascular hypoxia-reperfusion, inflammation and leukocytosis. Studies in SCD have shown that leukocytosis is a strong predictor of stroke and disease severity. It is known that leukocytosis and inflammation contribute to increased leukocyte-endothelial adhesion and vasoocclusive events. Leukocytosis or increased leukocyte number is determined by the balance between cell death programs (apoptosis) and proliferation. In this study, we examine markers of apoptosis and proliferation in SCD as compared to thalassemia (a hemoglobinopathy that is vasculitis negative) and a control group. Methods: Markers of leukocyte turnover, inflammation and free iron (NTBI, non-transferrin bound iron) were compared in 11 patients with SCD (7M, 13 ± 4 yrs), 18 with thalassemia (7M, 24 ± 9 yrs) and 10 disease-free controls (5M, 27 ± 12 yrs). All SCD and thalassemia patients were healthy and event free in the previous 4 months. Blood was obtained fasting and prior to RBC transfusion; and plasma, serum and cells were separated by centrifugation. The pro-apoptotic markers nucleosome protein (DNA laddering) and Bax (initiator of mitochondrial permeability) and inflammatory marker, high-sensitivity C Reactive Protein (hsCRP) were determined by ELISA. NTBI (DNA damage inducing, pro-apoptotic) was measured by HPLC. Plasma levels of cytokines (anti-apoptotic, proliferation stimulating) were determined by using a multiplex bead-based immunoassay. Plasma lactate dehydrogenase (LDH), a marker of hemolysis, was also measured because hemolysis products have been shown to inhibit apoptosis. Results: Leukocyte number and absolute neutrophil count were 1.8 and 2.2 fold higher in SCD compared to thalassemia (P&lt;0.01). Evidence for decreased apoptosis in SCD included reduced nuleosome protein as compared to thalassemia and reduced Bax as compared to controls. In addition, LDH was significantly increased 1.9 fold in SCD relative to thalassemia (p=0.012). In contrast, NTBI was 2 fold higher in thalassemia than SCD and correlated with nucleosome protein (R=0.45; p=0.013). Finally, high levels of the cytokines IL-6 and IL-10 in SCD relative to thalassemia may be stimulating leukocyte proliferation and survival. These cytokines and hsCRP are also positively correlated with leukocyte number. Conclusions: These preliminary findings demonstrate that the balance of apoptosis vs. proliferation favors delayed cell death and enhanced cell proliferation in SCD, leading to increased circulating leukocytes. These changes may be related to hemolysis, increased levels of inflammatory cytokines, and lower amounts of NTBI in SCD. This leukocytosis increases the potential for vasoocclusive events that contribute to stroke, acute chest syndrome or renal tubule damage.

Is Incentive Spirometry Effective in Preventing Post Surgical Acute Chest Syndrome in Sickle Cell Disease Patients?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4807-4807
Author(s):  
Adlette Inati ◽  
Fouad Ziade ◽  
Suzan Koussa ◽  
Ali Taher
Keyword(s):  
Postoperative Complications ◽  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Sickle Cell ◽  
Perioperative Care ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Clinical Events ◽  
Number Of Patients ◽  
Incentive Spirometry

Abstract Persons with sickle cell disease (SCD) are more likely to undergo cholecystectomy and splenectomy than are the general population. Even with meticulous care, surgical complications are seen in approximately 25% to 30% of patients. A chart review of SCD patients who had splenectomies and cholecystectomies and who were treated in 3 centers between1987–2007 was undergone. Data pertaining to clinical events, surgery, perioperative care and outcome were collected and analyzed. Since 1995, laparoscopic surgery was the modality used. Management consisted of preoperative transfusions in 83% of patients, general anesthesia, adequate hydration, temperature conservation, non sedating analgesia and supervised incentive spirometry exercises (after 1995) in all patients. The total number of patients was 120: 81 underwent splenectomy, 59 cholecystectomy and 20 both procedures. Of patients who underwent splenectomy, 43.2% were females and 56.8% males; 64.2% had sickle cell anemia (SCA) and 35.8% sickle-beta thalassemia (ST). For those undergoing cholecystectomy, 39.0% were females and 61.0% males; 79.7% had SCA and 20.3% ST. Patients undergoing splenectomy were significantly younger (mean age 9.28 years) than those undergoing cholecystectomy (mean age 15.28 years) (p=0.037). Median operative time was 50 minutes, and median hospitalization duration was 2 1/2 days. No major intra operative complications or fatalities were noted. Postoperative complications included acute chest syndrome (ACS) in 5 patients (4% of surgeries). The mean time to onset of symptoms of ACS was 36 hrs after surgery (range, 24–96 hr). All patients who developed this complication did not receive incentive spirometry or were noncompliant with this therapy. As for the relation between clinical events and splenectomy/cholecystectomy, bivariate analysis showed a significant association between splenectomy and regular blood transfusion (p=0.005). Borderline significance was found for the association of cholecystectomy with ACS, joint necrosis and stroke (0.05&lt;p&lt;0.10). Predictors of splenectomy were regular blood transfusion (OR=2.38, [1.36–4.17] 95%CI], ACS (OR= 3.42, [1.64–7.15] 95%CI) and ST as compared to SS (OR=1.89, [1.10–3.27] 95%CI). Predictors of cholecystectomy were regular blood transfusion (OR=2.02, [1.10–3.71] 95%CI and sepsis (OR=2.59, [1.04–6.45] 95%CI). Sensitive predictors of postoperative complications could not be studied due to the small number of complications. This survey shows that splenectomy and cholecystectomy can be performed in SCD patients with minimal morbidity and no mortality. The current rate (4%) of post surgical ACS is lower than previously reported and is probably due to strict adherence to meticulous perioperative care. The absence of post surgical ACS in patients treated with supervised incentive spirometry is suggestive of a beneficial effect of this therapy in preventing this serious complication. The small number of patients with post surgical ACS prevents us, however, from drawing definite conclusions about the preventive role of this treatment. Nevertheless, early use of this simple, available and inexpensive tool most likely minimizes surgical morbidity and mortality from ACS, decreases hospitalization time, cuts down expenses and can be helpful particularly in countries with limited resources. Prospective controlled studies are, however, warranted to evaluate the efficacy of incentive spirometry and other perioperative interventions in preventing complications in SCD patients undergoing surgery.

Prevalence of Sickle Cell Anemia In Eastern India

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4822-4822
Author(s):  
Abhijit Chakraborty ◽  
Jayasri Basak ◽  
Deboshree Majumdar ◽  
Soma Mukhopadhyay ◽  
Sagnik Chakraborty ◽  
...  
Keyword(s):  
Risk Factor ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
West Bengal ◽  
Conflicts Of Interest ◽  
Acute Chest Syndrome ◽  
Red Cell ◽  
Cell Disease ◽  
Cell Counts

Abstract Abstract 4822 Background: Sickle cell disease is an inherited disorder of hemoglobin synthesis. This is due to replacement of Valine for Glutamic Acid in position six of the Beta globin chain of hemoglobin. This genetic alteration yields unstable RBC which lasts for 10–20 days. In stressful conditions the cells become sickle shaped and get lysed. There are about 20 million people with sickle cell disease in India. During January 2009- May2010 camps were held in various parts of West Bengal, Jharkhand, Chattisgarh. Along with various mutations of thalassemia, we also observed sickle cell anemia among them. This triggered our interest to study the spectrum of the sickle mutation co-inheritant with different mutations such as Homozygous Sickle Cell, Sickle Cell-Beta0 Thalassemia, Sickle Cell-Beta+ Thalassemia, Severe β+ thalassemia genes, Moderate β+ thalassemia genes, Mild β+ thalassemia genes Sickle cell-HbE Thalassaemia, Sickle cell-HPFH Thalassaemia, in said part of India. Since Indian patients with SS disease had higher hemoglobin, red cell counts and higher HbF levels and lower HbA2, MCHC, MCV, and reticulocyte counts, hence a high hemoglobin is a risk factor for painful crises and may also be a risk factor for avascular necrosis of the femoral head, proliferative sickle retinopathy, and acute chest syndrome. Methods: We have screened 332 individuals in eastern part of India during the period January 2009- May 2010. 3ml of peripheral blood was collected in EDTA vial from each individual. NESTROFT (Naked Eye Single Tube Red Cell Osmotic Fragility Test) was performed on spot. Then Complete Blood Count was done within 24 hours of collection. HPLC (High Performance Liquid Chromatography) was performed to identify the samples for confirmation. In our observation in case of sickle cell anaemia HbF (Fetal haemoglobin), Hb (haemoglobin), MCV (mean corpuscular volume) values ranges between 0–10 %, ≤7-10g/dl, 65–90fl respectively. ARMS (Amplification Refractory Mutation System) PCR (polymerase chain reaction) was done to confirm the mutation. Result: Conclusion: Of the total samples collected in the camps held at various places of Jharkand, Chattisgarh & West Bengal 87 of them was carriers of sickle cell anemia. There was 7 homozygous (SS), 14 sickle beta, 12 double heterozygous for HPFH (High Persistance of Fetal Hemoglobin) & sickle cell anemia. In conclusion, the manifestations of sickle cell disease are influenced by a variety of other genetic and environmental factors. The occurrence of the disease against different genetic and environmental backgrounds provides experimental models that contribute to understanding the variability in clinical and hematological expression of the disease. Disclosures: No relevant conflicts of interest to declare.

Maintaining High Level Of Care At Outreach Sickle Cell Clinics

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2976-2976 ◽  
Author(s):  
Jennifer Hamm ◽  
Lee Hilliard ◽  
Thomas H. Howard ◽  
Jeffrey D. Lebensburger
Keyword(s):  
Health Care ◽  
Sickle Cell Disease ◽  
Medical Care ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Attendance Rates ◽  
Cell Disease ◽  
Major Health ◽  
Cell Network ◽  
Number Of Patients

Introduction Parents of children with sickle cell disease often seek care at large, university based sickle cell clinics. A major health care barrier for children in Alabama involves the cost and time of travelling to and from university based clinics. To reduce this health care barrier, the University of Alabama at Birmingham (UAB) developed The Children and Youth Sickle Cell Network(®) (CYSN(®)). This network consists of the central sickle cell clinic located at UAB and four outreach sickle cell clinics located in Montgomery (100 miles south of UAB), Opelika (110 miles southeast of UAB), Huntsville (100 miles north of UAB), and Tuscaloosa (60 miles west of UAB). The goal for these clinics is to maintain a similar level of medical care while reducing the health care barrier of transportation. Objective To determine if the outreach clinics provide similar care to university based clinics, we evaluated three surrogate preventive care markers to compare access to care in central vs. outreach clinics: 1) attendance rates, 2) number of patients on hydroxyurea, and 3) percent of MRIs obtained for screening of silent infarct among eligible patients. Methods A retrospective review of all CYSN(r) clinic visits from June 2012 to June 2013 was performed to determine clinic attendance rates. All patients on hydroxyurea were categorized by clinic location. Every patient attending CYSN(r) clinic between ages of 6 and 15 years had their medical record reviewed for completion of a screening MRI/MRA. Results At the central Birmingham clinic, the appointment show rate was 59.8% as compared to the Montgomery, Opelika, Huntsville, and Tuscaloosa show rates which were 57.7%, 73.1%, 59.4%, and 70% respectively. At UAB, institutional guidelines were developed for offering hydroxyurea to patients based on clinical indications and applied to all clinics. The percentage of patients on hydroxyurea therapy in Birmingham is 22.2%, while the percentages in Montgomery, Opelika, Huntsville, and Tuscaloosa are 21.5%, 32%, 21.4% and 24.4%, respectively. Finally, screening MRI/MRA to evaluate for evidence of silent cerebral infarctions is performed in Birmingham but offered to children ages 6-15 years at all sickle cell clinics. In Birmingham, 63.6% of eligible patients completed MRI/MRA screening. This percentage is similar for patients in Montgomery, Opelika, and Tuscaloosa who were screened at 66.7%, 83.3%, and 67.7% respectively. Conclusions Our data suggests that outreach clinics can provide similar levels of medical care for children with sickle cell disease. Sickle cell centers treating patients that must travel long distances should consider developing outreach clinics to help reduce this major health care barrier. Disclosures: No relevant conflicts of interest to declare.

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