scholarly journals Lung Vaso-Occlusion in Sickle Cell Disease Mediated By Arteriolar Neutrophil-Platelet Micro-Emboli

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 159-159
Author(s):  
Margaret F. Bennewitz ◽  
Ravi Vats ◽  
Egemen Tutuncuoglu ◽  
Mark T. Gladwin ◽  
Prithu Sundd
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Therapeutic Potential ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Fab Fragments ◽  
Pulmonary Arteriole ◽  
Biophysical Mechanism

Abstract Background: Vaso-occlusive crisis (VOC) is the primary reason for emergency medical care by sickle cell disease (SCD) patients. SCD patients hospitalized with VOC often develop acute chest syndrome (ACS), a form of acute lung injury, suggesting a role for pulmonary vaso-occlusion in the onset of ACS. However, the cellular, molecular and biophysical mechanism of pulmonary vaso-occlusion is unknown. Methods: SCD transgenic or non-sickle control mice were intravenously (IV) challenged with 2 to 3 ng of bacterial lipopolysaccharide (LPS). Fluorescent anti-mouse Ly-6G and CD49b mAbs were administered IV for in vivo staining of circulating neutrophils and platelets, respectively. Multiphoton excitation enabled quantitative fluorescence intravital lung microscopy (qFILM) was used to determine the molecular mechanism of pulmonary vaso-occlusion in live mice. Function-blocking anti-mouse P-selectin mAb (Fab fragments) was administered IV to assess the role of platelet P-selectin in promoting pulmonary vaso-occlusion. Results: A nanogram dose of IV LPS selectively triggered pulmonary vaso-occlusion in SCD but not control mice. Remarkably, pulmonary vaso-occlusion involved occlusion of the pre-capillary pulmonary arteriole bottle-necks (junction of an arteriole and capillaries) by large neutrophil-platelet embolic aggregates. IV administration of Fab fragments of function blocking anti-P-selectin mAb led to the resolution of pulmonary vaso-occlusion, which was primarily mediated by the attenuation of large neutrophil-platelet aggregates into smaller aggregates that are not stopped by the arteriolar bottle-necks. Conclusion: These results establish the relevance of neutrophil-platelet aggregation in pulmonary arterioles in promoting pulmonary vaso-occlusion in SCD and also highlight the therapeutic potential of inhibiting platelet P-selectin to prevent ACS in SCD patients hospitalized with VOC. Acknowledgments: This study was supported by 1R01HL128297-01 (P.S.), AHA 11SDG7340005 (P.S.), VMI startup funds (P.S.). M.F.B. was supported by NIH-NHLBI training grant T32HL110849 and NIH-NHLBI F32 NRSA 1F32HL131216-01. 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>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.

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 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.

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.

A Multicentre Study of Environmental Factors on the Severity of Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4841-4841
Author(s):  
Sanjay Tewari ◽  
Fred Piel ◽  
Valentine Brousse ◽  
Baba PD Inusa ◽  
Paul Telfer ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Environmental Factors ◽  
Sickle Cell ◽  
Hospital Admissions ◽  
Conflicts Of Interest ◽  
Acute Chest Syndrome ◽  
Electronic Patient Records ◽  
Cell Disease ◽  
Hospital Data ◽  
Significant Difference

Abstract Background: Sickle cell disease (SCD) is a very variable condition, with some patients being asymptomatic and others admitted frequently to hospital. Genetic factors have been extensively investigated but only explain a small amount of the variability to date. Environmental factors are undoubtedly important, but have not been studied in depth, at least in part because of the difficulty of conducting these studies. We have analysed the role of climatic, environmental and temporal factors in determining the frequency of hospital admissions in children with SCD to 4 large sickle cell centres in London and Paris. Participants and Methods: Clinical data were collected from 1st January 2007 to 31st December 2012. Inclusion criteria were children with SCD (HbSS and HbSC) between the ages of 0 and 17 years, admitted to hospital with acute pain, acute chest syndrome or fever. All children lived within 4 miles radius (London) or 10km (Paris) of the hospital. Data were collected using specific electronic patient records of SCD patients. Data were collected on the reason for admission, date and length of admission. Daily air quality records were collected from sites around Paris and London, including details of black smoke, particulate matter, nitric oxide, carbon monoxide, sulphur dioxide and ozone. Daily meteorological records were obtained from weather stations in London and Paris including wind speed, temperature, rainfall and humidity. Statistical analysis including time series studies were conducted using R software version 3.1.1. Results: There were a total of 2717 admissions over the six year study period. Overall for the London hospitals there was a mean of 0.39 admissions/patient/year, with 1406 admissions for pain, 153 for acute chest syndrome and 417 for fever. The rate of admission/patient/year by cause for HbSS and HbSC across the London hospitals is shown in table below: Table 1. Rates of admission/patient/year by cause Sickle genotype/cause of admission All London hospitals Institution A Institution B Institution C HbSS (Pain) 0.31 0.18 0.40 0.43 HbSS (Fever) 0.09 0.03 0.15 0.11 HbSS (acute chest syndrome) 0.04 0.03 0.04 0.04 HbSC (pain) 0.07 0.03 0.08 0.10 HbSC (fever) 0.03 0.01 0.04 0.05 HbSC (acute chest syndrome) 0.004 0.008 0.002 0.002 Overall admission numbers were significantly higher on Mondays and Tuesdays in London but there was no such variation in Paris (Table 2). Table 2. Mean number of admissions on days of week in Paris (1 hospital) and London (3 hospitals). ** denotes significant difference from mean of other days (P<0.001). London Paris Weekday Monday 0.75** 0.35 Tuesday 0.77** 0.36 Wednesday 0.66 0.36 Thursday 0.64 0.32 Friday 0.60 0.32 Saturday 0.51 0.20 Sunday 0.57 0.27 There was no seasonal variation in admission numbers in London, but significantly higher numbers of patients admitted in Paris during autumn and winter. Table 3. Mean number of seasonal admissions in Paris (1 hospital) and London (3 hospitals). ** denotes significant difference from mean of other days (P<0.001). London Paris Season Autumn 0.70 0.35** Spring 0.60 0.31 Summer 0.64 0.25 Winter 0.62 0.34** Conclusion In London, there is a 2-3 fold variation in admission rates for the same complications between different hospitals. Similarly there is a significant difference on the effects of season and weekday between Paris and London. These results are statistically stronger than many effects which are identified in genetic and therapeutic studies, and show the importance of environmental and cultural factors, which are potentially modifiable. The effect of weather and pollution on hospital admissions is currently being analysed. Disclosures No relevant conflicts of interest to declare.

Platelet-Neutrophil Aggregates Promote Pulmonary Arteriole Microembolism in Sickle Cell Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2162-2162
Author(s):  
Margaret F. Bennewitz ◽  
Ravi Vats ◽  
Egemen Tutuncuoglu ◽  
Mark T. Gladwin ◽  
Prithu Sundd
Keyword(s):  
Sickle Cell Disease ◽  
Molecular Mechanism ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Genetic Disorder ◽  
Acute Chest Syndrome ◽  
Cellular Trafficking ◽  
Anatomical Site ◽  
Cell Disease ◽  
Pulmonary Microcirculation

Abstract Introduction: Sickle cell disease (SCD) is an autosomal recessive genetic disorder that affects ~100,000 Americans and millions of people worldwide. The acute chest syndrome (ACS), a form of acute lung injury, is a major cause of morbidity among SCD patients. The current treatment for ACS is primarily supportive and the molecular mechanism remains largely unknown. SCD patients hospitalized with vaso-occlusive pain crisis (VOC) often develop ACS within the ensuing days, suggesting a role for pulmonary vaso-occlusion in the onset of ACS. However, the cellular and molecular mechanism and the anatomical site of pulmonary vaso-occlusion are still elusive. Materials and Methods: Intravenous (IV) bacterial lipopolysaccharide (LPS) was used to induce VOC in SCD mice. Intravital multiphoton excitation (MPE) fluorescence microscopy was used to study the blood cell trafficking within the pulmonary microcirculation of live SCD or control mice. Fluorochrome-conjugated anti-mouse Ly-6G, Ter-119, and CD49b antibodies were administered IV for in vivo staining of circulating neutrophils, red blood cells and platelets, respectively. Cellular trafficking was recorded at baseline and 2 hours after IV challenge with LPS. Image sequences were analyzed to identify vaso-occlusion, which was defined as cellular aggregation and stasis of blood flow within the pulmonary blood vessels. Results and Discussion: Preliminary data using MPE imaging in transgenic SCD mice revealed that vaso-occlusion was absent at baseline in unchallenged SCD mice and the cellular trafficking within the pulmonary microcirculation was comparable in SCD and control mice. Doses of IV LPS (0.01-5 mg/kg of body weight), which were innocuous to control mice were found to be lethal to SCD mice. Remarkably, MPE imaging of the lung microcirculation revealed that IV LPS led to microembolism of the pre-capillary pulmonary arterioles by platelet-neutrophil aggregates in SCD but not control mice. The microembolism involved either entrapment of circulating platelet-neutrophil aggregates or in situ aggregation through sequential steps of neutrophil arrest on the arteriolar endothelium, followed by platelet nucleation on arrested neutrophils and microthrombus formation. Conclusions: Initial findings demonstrate that pulmonary vaso-occlusion in SCD mice involves microembolism of the pre-capillary pulmonary arterioles by platelet-neutrophil aggregates. Future studies will determine the molecular interactions responsible for pulmonary arteriolar microembolism. Acknowledgments: This study is supported by the 11SDG7340005 from the American Heart Association (P.S.) and the VMI startup account (P.S.). M.F.B is supported by the NIH NHLBI VMI T32 training grant T32HL110849. Disclosures No relevant conflicts of interest to declare.

scholarly journals Spontaneous Calvarial Infarction with Epidural Hematoma and Subgaleal Hemorrhage in a Teenager with Sickle Cell SS Disease and Glucose-6-Phosphate Dehydrogenase Deficiency

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4168-4168
Author(s):  
Jennifer Nestor ◽  
Danielle Sanders ◽  
Sukrita Mysore ◽  
Rafat Ahmed ◽  
Aubri Milano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Epidural Hematoma ◽  
Vision Loss ◽  
Conflicts Of Interest ◽  
Hypovolemic Shock ◽  
Acute Chest Syndrome ◽  
Significant Finding ◽  
Cell Disease

Abstract Introduction: Sequelae of sickle cell disease (SCD) are often the result of vaso-occlusion (VOC) related to the dysmorphic shape of sickled red blood cells (RBC). Bone infarction occurs commonly in patients with sickle cell, most notably in long bones and axial skeleton. Infarct occurs much less frequently in the bones of the skull. Calvarial bone infarct results in MRI findings of T2 hyperintensity in areas of bone marrow edema with associated swelling or hemorrhage. Symptomatic headaches in children with SCD are more likely to be due to severe underlying cerebral pathologies than in those children without SCD. When evaluating a child with SCD presenting with headache, it is important to consider calvarial infarct. Case Description: A 15 year old male with a history of sickle cell disease (type SS) and G6PD deficiency presented with chief complaints of headache and swelling over the left parietal region of the skull for two days with associated left sided visual disturbance. He denied head trauma or seizure-like activity. Upon presentation he was febrile with tachycardia and a normal neurological exam. CT scan of his head was significant for a left subgaleal hemorrhage and bilateral epidural midline and left parietal fluid collections consistent with bone marrow infarcts and associated subacute epidural hematomas, without evidence of brain parenchymal injury or sinus venous thrombosis. A follow up MRI obtained during hospitalization indicated that the left subgaleal hematoma remained stable with breakdown of subgaleal blood products. The patient was treated primarily with supportive care including hydration, packed red blood cell transfusions and pain management. He did not require neurosurgical intervention. His hospital course was complicated by VOC, sickle cell hepatopathy and acute chest syndrome. Discussion: Rarely, cranial VOC has resulted in epidural hematoma. In this case, calvarial infarct with unilateral headache, acute vision loss and acute cranial swelling resulted in subgaleal hemorrhage. This clinically significant finding results from bleeding between the periosteum and scalp galea aponeurosis, which may lead to hypovolemic shock. Calvarial infarcts should be considered on the differential in sickle cell disease patients presenting with a headache as prompt diagnosis can improve morbidity outcomes. Disclosures No relevant conflicts of interest to declare.

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