scholarly journals Sickle Cell Disease and Vestibular Dysfunction

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4183-4183
Author(s):  
Nicholas S Andresen ◽  
Tiffany McIntyre ◽  
Bryan K Ward ◽  
Melanie Dawn Nelson ◽  
Amir Kheradmand ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sickle Cell Disease ◽  
General Population ◽  
Sickle Cell ◽  
Research Funding ◽  
Cell Structure ◽  
Vestibular Dysfunction ◽  
Cell Disease ◽  
Increased Risk ◽  
Privately Held

Abstract Introduction: Sickle cell disease (SCD), a common genetic disease involving red blood cell structure and function, is associated with cerebral vasculopathy and increased risk of ischemic events that may also affect the inner ear. Individuals with SCD are at increased risk for hearing loss; however, little is known regarding the effects of SCD on the vestibular system or the relationship between hearing loss and vestibular symptoms in these patients. Vestibular dysfunction affects 15-20% of the general population can lead to significant morbidity through falls, fall-related injuries, missed work, and overall reduction in quality of life. Methods: To assess the burden of vestibular dysfunction amongst individuals with SCD, we surveyed individuals with SCD who answered questions about symptoms of dizziness, imbalance, and hearing loss. The survey also captured demographic information, current symptoms of dizziness/imbalance, symptoms of hearing loss, and history of falls. Fisher's exact test was performed to test for associations between clinical characteristics including SCD genotype, hearing loss, dizziness or imbalance, and headache history. Results: Twenty-six participants, ages 20 to 73 years (median 37.5 years) completed the survey. All participants were Black or African-American. Five participants (19.2%) were male, 15 (58%) had hemoglobin SS, 8 (32%) hemoglobin SC, and 3 (12%) S-β + thalassemia. Three (11.5%) participants reported hearing loss. Twelve (46.2%) participants reported dizziness or imbalance, of which 8 (66%) reported recent falls. Of the 12 participants experiencing dizziness, 9 (75%) reported having dizziness for 1 to 3 days a month, 2 reported having dizziness for 4 to 9 days a month, and 1 reported having dizziness for more than 15 days a month. Three participants reported their dizziness symptoms resolved within seconds, 7 within minutes, and 2 within hours. Eleven (42.3%) participants reported headaches. Self-reported dizziness or imbalance was not associated with hearing loss (X 2=0.57; p=0.45), SCD genotype (X 2=0.75; p=0.68), or sex (X 2=0.09; p=0.76). Headache history was associated with dizziness or imbalance (X 2=9.76; p=0.002). Conclusions: In this small pilot study, 46% of individuals with SCD reported dizziness or imbalance, which is twice the rate reported amongst the general population. Headache history is associated with dizziness and imbalance amongst individuals with SCD. Further investigation is warranted to determine the specific effects of SCD on the vestibular end-organs. Disclosures Lanzkron: Imara: Research Funding; Pfizer: Current holder of individual stocks in a privately-held company; GBT: Research Funding; Shire: Research Funding; Teva: Current holder of individual stocks in a privately-held company; Novartis: Research Funding; Novo Nordisk: Consultancy; Bluebird Bio: Consultancy; CSL Behring: Research Funding. Lance: Novartis: Other: participated in research advisory board in 2020.

scholarly journals COVID-19 in Hospitalized Patients with Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3090-3090
Author(s):  
Stephanie Guarino ◽  
Sophie M. Lanzkron
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Case Fatality ◽  
Hospitalized Patients ◽  
Categorical Variables ◽  
Fatality Rate ◽  
Cell Disease ◽  
Increased Risk ◽  
Privately Held

Abstract Introduction Sickle cell disease (SCD) is the most common inherited hemoglobinopathy and is estimated to affect more than 100,000 Americans. Current Centers for Disease Control statistics indicate that Black Americans die from COVID-19 at a disproportionately high rate, 13.6% of 449, 373 deaths but only account for 12.54% of the United States Population (CDC COVID Data Tracker accessed 5/5/2021). A voluntary clinical reported registry of COVID-19 infections in patients with SCD reported both high hospitalization rates (69%) and case fatality rates (7%) (Panepinto, 2020), but only reported data from March 20-May 21, 2020. A retrospective cohort review from England demonstrated a 4-fold increased risk of hospitalization and 2.6-fold increased risk of death due to COVID-19 for those patients with sickle cell disease compared to the general population (Hippisley-Cox, 2021). The unique constellation of SCD manifestations complicate both the diagnosis and management of COVID-19, particularly related to anticoagulation and transfusion practices. Understanding the impact of early exchange and anticoagulation would guide development of appropriate treatment guidelines and future understanding of pathophysiology. We report on the outcomes for all hospitalized inpatients with SARS-CoV-2 and SCD at institutions using Cerner electronic health record (EHR). Methods Exempted retrospective review approved by ChristianaCare IRB. We obtained deidentified data from the Cerner COVID Data Lab which includes information on all hospitalized inpatients with SARS-CoV-2 and sickle cell disease as documented by ICD 10 D57.XX from 12/10/2019-10/15/2020 at institutions that use the Cerner EHR. Those with sickle cell trait excluded. The data included 209 patients; 1 patient had separate 2 visits, only the first visit in the data. Evaluated anticoagulation use, not dose. Descriptive statistics are given: percentages for categorical variables and mean (standard deviation) for continuous variables. Comparisons between patients who died or went to hospice versus patients who recovered were done using unadjusted chi-squared tests or t-tests. Results: Admission: 124 (74.3%) were afebrile (temp <100) 52 (28.4%) were tachypneic (RR >22) 10 (6.2%) were hypoxic (<92%) 7 (3.3%) were intubated during hospitalization Many patients had comorbidities including diabetes, hypertension, and congestive heart failure, but it was not clear if patients had multiple co-morbidities. Treatment: 16 (7.7%) got transfused RBC between 1.77 and 589.18 hours into admission 5 (2.4%) got Remdesivir, none of these patients died/went to hospice. No exchange transfusions, but maybe wasn't captured in coding data 149 (71.3%) received anticoagulant, dosing unable to be obtained so not known if this was prophylactic or treatment dosing. Outcomes: 158 (80.2%) discharged home 18 (9.1%) discharged facility 8 (4.1%) died 2 (1.0%) discharged hospice 11 (5.6%) left against medical advice 12 (5.7%) missing disposition data Those who died/went to hospice had longer hospital stays, were more likely to be hypoxic and initially tachypneic. None of these patients received remdesivir. Study included small numbers but those who died more likely to have hypertension, diabetes w/ and w/out complications, CHF. Discussion This data only included hospitalized patients, doesn't account for patients who remained outpatient so case fatality rate likely lower. 10/209 patients died- 4.8% fatality rate, 12 patients missing final discharge disposition. 18 went to facility, may have died as outpatient. Only a small number of patients received remdesivir and there were overall low rates of anticoagulation, concerning given SCD is a hypercoagulable state. Study limitations include only hospitalized patients in the dataset and only draws from Cerner EMR institutions, a 26% market share. Based on our own SCD population, only a small percentage of patients with SCD and COVID-19 hospitalized. Additionally, there is likely significant variability between institutions' treatment protocols, particularly in the early months of the data set. Finally, we could not adequately gauge severity of COVID-19 disease given notable variations in institutional resources. TABLES (in process): TABLE 1- Demographics- split by death/hospice vs. other dispositions TABLE 2- Admission Characteristics- Death/hospice vs. others TABLE 3- Treatments- Death/Hospice vs. others Disclosures Lanzkron: Shire: Research Funding; Novartis: Research Funding; Bluebird Bio: Consultancy; CSL Behring: Research Funding; Imara: Research Funding; GBT: Research Funding; Pfizer: Current holder of individual stocks in a privately-held company; Teva: Current holder of individual stocks in a privately-held company; Novo Nordisk: Consultancy.

Alloantibody Formation In Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2395-2395 ◽  
Author(s):  
Joep Sins ◽  
Saurabh Zalpuri ◽  
Marjon Cnossen ◽  
Anita W. Rijneveld ◽  
Jean-Louis Kerkhoffs ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
General Population ◽  
Sickle Cell ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Cumulative Number ◽  
Cell Disease ◽  
Cox Regression Analysis ◽  
Increased Risk

Abstract Background Transfusion of red blood cells (RBC) is a common intervention to treat and prevent complications in sickle cell disease (SCD). However, frequent transfusions may lead to erythrocyte alloimmunization, thereby complicating donor matching procedures and posing patients at risk for hemolytic transfusion reactions. Little information is available about the risk of alloimmunization of sickle cell patients living in European countries. In the Netherlands extensive matching procedures to prevent alloimmunization were introduced a decade ago, but the effect on alloimmunization has not been evaluated yet. Aims The primary aim of this study is to evaluate the cumulative incidence of first alloantibody formation in a Dutch cohort of transfused SCD patients, and to compare this with a general Dutch RBC-transfused population. In addition, the effect of extended RBC matching protocols on the incidence of alloantibody formation in SCD and potential clinical determinants of alloimmunization will be assessed. Methods We conducted a retrospective cohort study and collected data on SCD patients (genotypes HbSS, HbSC, HbSβ0 and HbSβ+ thalassemia), diagnosed in three Dutch Sickle Cell Treatment Centers that received non-extended matched (ABO, RhD) RBC transfusions between 1984-2004 and extended matched (at least ABO, Rhesus phenotype, Kell) RBC transfusions between 2004-2011. In addition, we compared this population with a general population of 3 042 patients that received non-extended matched (ABO, RhD) RBC transfusions between 2005-2009 in the Leiden University Medical Center (Zalpuri et al. 2012). Cohorts were not matched for ethnicity. Alloimmunization risk was calculated as Kaplan-Meier incidence with cumulative number of transfusions as time variable. The association with the clinical determinants gender, SCD-phenotype and ethnicity was analyzed with Cox-regression analysis. Results A total of 291 SCD patients received 7 957 RBC units. Alloantibody formation occurred in 52 (17.9%) patients. The cumulative incidence of alloimmunization was 9% after 5 RBC units, 15% after 10, 24% after 20 and 34% after 40 RBC units. Multivariate analysis, correcting for the cumulative number of transfusions, demonstrated a significantly increased risk of alloantibody formation in our SCD cohort when compared to a general population of transfused patients (HR 7.5 (95% CI: 5.06-11.14), where the cumulative incidence of alloimmunization was 1.1% after 5, 2.4% after 10, 3.4% after 20 and 6.5% after 40 RBC units. No association could be demonstrated between alloantibody formation and clinical determinants such as gender, SCD-phenotype or ethnicity. However, a significant reduction in alloimmunization was observed in SCD patients that received their first transfusion from the year 2004 onwards, after preventive matching for Rhesus phenotype and Kell was introduced for SCD patients (HR 0.48 (95% CI: 0.24-0.97)). Conclusion The overall rate of first RBC alloantibody formation in our cohort was 17.9% and the risk of alloimmunization increased substantially with an increasing number of RBC transfusions. A unique comparison with a general cohort of Dutch transfused patients demonstrates a significantly higher risk of alloantibody formation in SCD, acknowledging earlier findings. This may partially be explained by differences in RBC antigens between patients of African descent and the predominantly Caucasian donors. Besides the number of RBC units, no other clinical risk factors for allo-immunization in SCD could be identified. The effectiveness of extended RBC matching protocols in the prevention of alloimmunization for chronically transfused patients in the participating centers was confirmed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Regulatory Genetic Variation at the S100B Gene Associates with Vaso-Occlusive Manifestations in Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1063-1063 ◽  
Author(s):  
Xu Zhang ◽  
Wei Zhang ◽  
Santosh L. Saraf ◽  
Sergei Nekhai ◽  
Mark T Gladwin ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Research Funding ◽  
Genetic Regulation ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Thrombotic Risk ◽  
Increased Risk

Abstract In sickle cell disease (SCD) polymerization of hemoglobin S under deoxygenated conditions causes vaso-occlusion, which can manifest as acute pain crisis and progressive bone/organ damage. Molecular studies have attributed vaso-occlusion to elevated vascular adhesion and inflammatory responses, whereas the genetic regulation has only recently been assessed. Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) was hybridized to Illumina Human 610-Quad SNP array for the PUSH and Walk-PHaSST cohorts and to Affrymetrix SNP 6.0 array for the Howard SCD expression cohort. Single nucleotide polymorphisms (SNPs) for 381 PUSH, 525 Walk-PHaSST, and 55 Howard patients were imputed to 1000 genomes project phase 3 data. Messenger RNA from PBMCs was profiled using Affymetrix Human Exon 1.0 ST Array for the Howard expression cohort and Affymetrix Human gene 2.0 ST array for the UIC expression cohort. Patients within the PUSH and Walk-PHaSST cohorts were classified to four groups according to a cumulative pain score, calculated based on pain frequency and questionnaire description of pain intensity. Pain grouping was examined for correlation with other SCD complications using Cochran Armitage test. History of acute chest syndrome (ACS, PUSH P=3.8×10-9, Walk-PHaSST P=2.4×10-5) and avascular necrosis (AVN, PUSH P=4.1×10-4, Walk-PHaSST P=3.7×10-5) were the most significant clinical manifestations that consistently associated with pain in the two cohorts. To investigate the genetic control of vaso-occlusive manifestations with appropriate power, we leveraged genetic association of pain, ACS, and AVN with genetic regulation of disease-specific gene expression. We mapped expression quantitative trait loci (eQTL) in the Howard expression cohort for SNPs<1 Mb away from gene ends per expression trait. At a permutation based false discovery rate of 5%, 1004 independent eQTL (linkage disequilibrium r2 ≤0.3 per trait) were identified for 880 genes. Focusing on 129 genes whose expression was altered in PBMCs in sickle cell anemia by at least 1.5-fold [1], we identified six eQTL for five differential genes (up-regulated: OSBP2, SLC14A1, RNF182, CCRL2; down-regulated: S100B). The six eQTL were assessed for association with pain, ACS, and AVN, using the Walk-PHaSST cohort for discovery and the PUSH cohort for validation. At a significance of Bonferroni corrected P=0.05 (nominal P=0.0083), an eQTL of S100B (rs2154586) significantly associated with AVN in the Walk-PHaSST cohort (OR=1.8, P=0.00061) and the association was replicated in the PUSH cohort (OR=2.7, P=0.0052). The A allele of the eQTL (frequency=0.18) associated with increased risk for AVN and increased expression level of S100B in the Howard expression cohort (β=0.40, P=1.6 ×10-6). In an additional 64 sickle cell anemia patients without hydroxyurea treatment from the UIC expression cohort, expression levels of S100B were significantly elevated in the individuals with AVN (β=0.28, P=0.029). The 24 SNPs in linkage disequilibrium with the eQTL (r2 >0.7) constituted the third most significant peak in a meta-analysis of genome-wide association of AVN in the PUSH and Walk-PHaSST cohorts. To test the hypothesis that genes involved in vaso-occlusion in SCD may affect thrombotic risk in non SCD individuals, we examined the association of the locus with venous thromboembolism (VTE) in the ARIC, JHS and CHS cohorts from dbGaP. The locus was imputed in African Americans and VTE was defined as being told by a doctor to have a blood clot in the leg or lung as answered in questionnaires during medical exams. The SNPs were associated with VTE using logistic linear regression adjusting for age, gender, enrollment site, and the first 15 principal components per cohort. The risk allele of the leading SNP for AVN consistently associated with increased risk of VTE across the cohorts, with a combined P=0.0041 and OR=1.4. S100B encodes a calcium sensor that appears to intervene in a variety of biological functions. S100B can mediate the inflammatory effects of damage-associated molecular pattern molecules (DAMPs) produced by erythrocyte hemolysis [2, 3]. Serum concentration of S100B correlates with LDH and with TCD-determined peak velocity of the left middle cerebral artery in thalassemia patients[4]. Polymorphisms of S100B that lead to increased serum levels are associated with increased risk of ischemic stroke in the Chinese population[5]. Disclosures Nekhai: NIMHD, NIH: Research Funding; NHLBI, NIH: Research Funding; NIAID, NIH: Research Funding.

scholarly journals Risk of Hospitalization for Vaso-Occlusive Episode in Patients with Sickle Cell Disease after out-Patient Exposure to Systemic Corticosteroids

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2048-2048
Author(s):  
Ondine Walter ◽  
Pierre Cougoul ◽  
Julien Maquet ◽  
Pablo Bartolucci ◽  
Maryse Lapeyre-Mestre ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Board Of Directors ◽  
Sickle Cell ◽  
Research Funding ◽  
Cell Disease ◽  
National Health Insurance System ◽  
Advisory Committees ◽  
Systemic Corticosteroids ◽  
Increased Risk ◽  
Case Period

Abstract Introduction : Sickle cell disease (SCD) is an inherited disorder which affects 300,000 newborns per year. Vaso-occlusive episodes (VOEs) cause an important morbi-mortality and a decreased quality of life in patients with SCD. Some risk factors of VOE are well known, like infection, cold exposure, stress, pulmonary diseases and dehydration. Exposure to systemic corticosteroids has been suspected to increase the occurrence of VOEs in few case reports or series. However, no comparative study has been conducted to demonstrate this risk which is still debated, resulting in discrepancies among guidelines on SCD management. This study aimed to assess the risk of hospitalization for VOE associated with out-hospital exposure to systemic corticosteroids in patients with SCD in France. Methods : Data source was the French national health insurance system database, named SNDS (Système National des Données de Santé) between 2010 and 2018. The SNDS links sociodemographic, out- and in-hospital data for the entire French population (&gt;66 million inhabitants). The study population consisted in all patients with SCD with at least one hospitalization for VOE during the study period, identified with a primary discharge diagnosis of VOE (D57.0 code of the international classification of disease, 10 th version; positive predictive value: 98.6%). All genotypes (homozygous SS-SCD and double-heterozygous SCD) were included. Because we assessed out-hospital exposure to corticosteroids, patients hospitalized during the three months before the first VOE were excluded. We performed a case-case-time-control study (Figure 1). This self-controlled design results in self-adjustment for time-independent confounders, including genotype. The outcome was the first hospitalization for VOE. The exposure to oral and injectable corticosteroids, identified using out-hospital reimbursement data, was assessed during a case period (28 days before the outcome) compared to the exposure during a control period (28 days, starting 84 days before the outcome). The same comparison was made among future cases (matched patients hospitalized for VOE the year after the given case), in order to adjust for the trend of exposure to corticosteroids (calendar variations of corticosteroid exposure). Results : Overall, 5,151 cases of VOEs were included in the main analysis. Median age at first VOE was 16.9 years; 317 (6.2%) patients were exposed to corticosteroids during the case period. In the main analysis, corticosteroid exposure was significantly associated with the occurrence of hospitalizations for VOEs: adjusted Odds Ratio (aOR): 3.81, 95% confidence interval (95% CI): 2.44 to 5.61. In patients exposed to hydroxyurea, the aOR was 2.61, 95% CI: 1.07 to 6.39, compared with an aOR of 4.00, 95% CI: 2.53 to 6.30 in unexposed patients. In the subgroup analysis by age, the aOR was 2.81, 95% CI: 1.49 to 5.30 in children, and 4.45, 95% CI: 2.37 to 8.37 in adults. The results were consistent in all sensitivity analyses. Conclusion : This study showed an association between outpatient exposure to systemic corticosteroids with an increased risk of hospitalization for VOE, in both adults and children. Hydroxyurea may reduce this risk in adults. Figure 1 Figure 1. Disclosures Bartolucci: GBT: Consultancy; Emmaus: Consultancy; Fabre Foundation: Research Funding; AGIOS: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Jazz Pharma: Other: Lecture fees; INNOVHEM: Other: Co-founder; Bluebird: Consultancy, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy; Hemanext: Consultancy; Addmedica: Consultancy, Other: Lecture fees, Research Funding. Moulis: Argenx: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Higher Prevalence of Autoimmune Diseases in Patients with Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 982-982
Author(s):  
Man Wai Tang ◽  
Erfan Nur ◽  
Charlotte F.J. Van Tuijn ◽  
Bart J. Biemond
Keyword(s):  
Sickle Cell Disease ◽  
General Population ◽  
Autoimmune Diseases ◽  
Chronic Inflammation ◽  
Sickle Cell ◽  
Research Funding ◽  
Patient Characteristics ◽  
Organ Damage ◽  
Cell Disease ◽  
Inflammatory State

Abstract Introduction Sickle cell disease (SCD) affects millions of people throughout the world. This is caused by a mutation in the hemoglobin gene resulting in abnormal red blood cells. Patients with SCD are in a state of chronic inflammation that is driven by ongoing hemolysis and ischemia-reperfusion injury due to recurrent vaso-occlusions.(1) It is also known that infections occur more frequently in patients with SCD. Abundant literature support the role of infections, interacting with the immune system as the so-called second hit in the cascade towards development of autoimmune diseases.(2) The chronic inflammation together with genetic predisposition and environmental factors can potentially lead to an auto-inflammatory state and/or disease. Recently, a study has shown a prevalence of autoimmune diseases (AID) of 1,3% in SCD patients between 7 and 17 years of age, although not compared to the general population.(3) Our hypothesis is that due to the chronic inflammation the prevalence of autoimmune diseases in adult patients with SCD are much higher compared to the general population. The aim of the study was to evaluate the proportion of patients with and without an AID. Methods Between 2004 and 2021, patients with SCD aged above 18 were seen at the outpatient clinic at the Amsterdam University Medical Center in Amsterdam. We performed a retrospective study in adult SCD patients to assess the prevalence of AID in SCD. AID was defined as: disease with the presence of autoantibodies and/or auto-reactive lymphocytes becoming involved in inflammation, which develop pathological autoimmunity and finally leads to tissue damage. We have selected 35 most common autoimmune diseases. A total of 338 patients with SCD were eligible and included in the study. The patient characteristics were summarized in Table 1. The previously reported prevalence of the AID in the African-American population was used to compare the prevalence in our study cohort. In addition, risk factors for AID and relation with organ damage was analyzed. Results AID was diagnosed in 36/338 patients with SCD. The prevalence of AID in this cohort is 10,7% compared to 4.7% in the general population (see table 2). There was no difference in patient characteristics (age, sex, genotype) between the SCD patients with or without AID. The BMI was higher in the group of patients with autoimmune diseases, although not statistically significant. In patients with SCD, the most frequent (&gt;1%) diagnosed AID were: sudden deafness (1.8%), hyper- and hypothyroidism (3%) and sarcoidosis (1.2%). With respect to organ damage, a significantly high rate of retinopathy was observed in SCD patients with AID as compared to SCD patients without AID (53% and 29% respectively, p=0.005). Furthermore, a trend towards more frequently microalbuminuria was found in SCD patients with AID 14/36 (39%) as compared to patients without AID 69/302 (23%). Conclusions This study showed for the first time a higher prevalence of autoimmune diseases in adult patients with SCD compared to previous reported in the general population. In patients with AID, a trend towards more microalbuminuria and significantly higher rate of retinopathy were observed. These findings support the hypothesis that the chronic inflammatory state in SCD patients may be related to the development of AID. Further research is needed to find strategies to target the chronic inflammatory state in order to prevent the development of AID. References 1. Nader E, Romana M, Connes P. The Red Blood Cell-Inflammation Vicious Circle in Sickle Cell Disease. Front Immunol. 2020;11:454. 2. Ercolini AM, Miller SD. The role of infections in autoimmune disease. Clin Exp Immunol. 2009;155(1):1-15. 3. Li-Thiao-Te V, Uettwiller F, Quartier P, Lacaille F, Bader-Meunier B, Brousse V, et al. Coexistent sickle-cell anemia and autoimmune disease in eight children: pitfalls and challenges. Pediatr Rheumatol Online J. 2018;16(1):5. Figure 1 Figure 1. Disclosures Nur: Celgene: Speakers Bureau; Roche: Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Biemond: Global Blood Therapeutics: Honoraria, Research Funding, Speakers Bureau; Sanquin: Research Funding; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Celgene: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau.

scholarly journals Clinical Outcomes and Healthcare Utilization in Patients with Sickle Cell Disease: A Nationwide Cohort Study of Medicaid Beneficiaries

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3459-3459
Author(s):  
Rishi J Desai ◽  
Mufaddal Mahesri ◽  
Raisa Levin ◽  
Denise Globe ◽  
Krista McKerracher ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Board Of Directors ◽  
Sickle Cell ◽  
Research Funding ◽  
Cell Disease ◽  
Advisory Committees ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Ed Visits ◽  
Event Rates

Introduction: There is limited contemporary evidence on clinical outcomes and healthcare use in sickle-cell disease (SCD) patients enrolled in US Medicaid. We aimed to provide contemporary estimates for rates of vaso-occlusive crises (VOC), mortality, and healthcare resource utilization (HRU) in SCD patients enrolled in US Medicaid. Methods: We conducted a cohort study using nationwide Medicaid insurance claims data (2000-2013). Patients were included based on ≥1 inpatient or ≥2 outpatient HbSS SCD diagnosis claims after 365 days continuous enrollment in Medicaid (or continuous eligibility since birth if age at diagnosis is &lt;1 year). Patients were followed until Medicaid disenrollment, death, bone marrow transplant, or end of data availability (December 31, 2013). Outcomes included frequency of VOCs, event rates of HRU including emergency department (ED) visits, hospitalizations, outpatient visits, and blood transfusions, and all-cause mortality during the follow-up period. All outcomes were reported as annualized event rates (with 95% confidence intervals). VOCs were stratified by age-group (&lt;1, 2-6, 7-12, 13-18, 19-35, 35+ years), VOCs at baseline (&lt;2, 2-4, &gt;=5), race (African American or not), and sex. The impact of VOCs on the risk of mortality was analyzed using an extended multivariable Cox model with VOCs modeled as time-varying and updated annually. Results: A total of 44,033 SCD patients were included in the analysis; 47% were female, 82% were African American, and a mean (SD) age of 15.7 (13.6). The average VOC rate was 3.71 (95% CI: 3.70-3.72) VOCs per person-year over an average follow-up period of 4.3 years. The rate of VOCs was substantially higher among patients aged 19-35 years and those with a higher VOC frequency at baseline (Table 1). Overall, the event rates (95%CI) per person year for other HRU outcomes were: 2.97 (2.97-2.98) ED visits, 2.39 (2.38-2.40) hospitalizations, 5.80 (5.79-5.81) outpatient visits, and 0.91 (95%CI: 0.90-0.91) blood transfusions. The mortality rate was 1.13 (95%CI: 1.08-1.17) events per 100 person-years overall, with the highest rate being 4.91 (95%CI: 4.58-5.25) events per 100 person-years among patients ≥ 35 years of age. Higher VOC burden in the preceding year was associated with an increased risk mortality: 2-4 VOC vs. 0 or 1 VOC: Hazard Ratio (HR)=1.36 (95%CI: 1.21-1.52); ≥ 5 VOC: HR= 1.56 (95%CI: 1.39-1.75). Conclusion: The burden of SCD in US Medicaid enrollees is substantial, especially during early adulthood, with markedly high rates of VOCs, mortality, and healthcare utilization. A higher VOC rate in the preceding year was associated with an increased risk of mortality suggesting a need for careful management of SCD patients with higher VOC burden. Table 1. Annualized rates of vaso-occlusive crises (VOC) among sickle cell disease patients enrolled in Medicaid. VOC, vaso-occlusive crises; CI, confidence interval. Table 1 Disclosures Desai: Merck: Research Funding; Bayer: Research Funding. Globe:Vertex Pharmaceuticals Incorporated: Employment. McKerracher:CRISPR Therapeutics: Employment. Mutebi:Vertex Pharmaceuticals Incorporated: Employment. Bohn:Bohn Epidemiology: Equity Ownership; Vertex Pharmaceuticals Inc: Consultancy. Achebe:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pharmacosmos: Membership on an entity's Board of Directors or advisory committees; Fulcrum Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees. Schneeweiss:Genentech: Research Funding; Boehringer Ingelheim: Research Funding; Aetion, Inc.: Consultancy, Equity Ownership; Whiscon LLC: Consultancy.

scholarly journals COVID-19 and Sickle Cell Disease in the Province of Quebec: Morbidity and Mortality Rates Derived from the Provincial Registry

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4064-4064
Author(s):  
Mathias Castonguay ◽  
Nawar Dakhallah ◽  
Marie-Laure Colaiacovo ◽  
Camille Jimenez-Cortes ◽  
Justin Desroches ◽  
...  
Keyword(s):  
Public Health ◽  
Risk Factors ◽  
Sickle Cell Disease ◽  
General Population ◽  
Sickle Cell ◽  
Death Rate ◽  
Research Funding ◽  
Mortality Rates ◽  
Cell Disease ◽  
History Of

Abstract Introduction Approximately 1500 people live with sickle cell disease (SCD) in the province of Quebec, Canada. Public health has recognized these patients as immunocompromised. SCD patients may be at higher risk of developing severe COVID-19 infection due to their underlying pro-inflammatory and thrombogenic state, splenic dysfunction and secondary organopathies. Descriptions about disease severity and mortality rates in SCD vary widely. From the SECURE-SCD registry, Mucalo et al. recently reported a 0.3% and 4.7% mortality rate in children and adults, respectively. In the French registry, Arlet and colleagues reported a 2.4% death rate among those hospitalized with COVID-19 and SCD, not different from the general population. As a result, the COVID-19 morbidity and mortality rates among the SCD population remain uncertain. Objectives The primary objectives of our study are to describe the epidemiology, baseline characteristics and clinical outcomes of SCD patients with COVID-19 infection in the province of Quebec. In addition, we aim to identify risk factors for hospitalization and severe forms of COVID-19. Methods We built a web-based SCD-COVID-19 registry regrouping 7 adult and 4 paediatric tertiary care hospitals in the province of Quebec in June 2020. All SCD patients with a confirmed SARS-CoV-2 infection by PCR test were included in the study. We compared the prevalence of infection and hospitalization rates of SCD patients to the general population of Quebec using the epidemiological data from the INSPQ (National Institute of Public Health of Quebec) public database. We retrospectively analyzed data included between March 11, 2020 to March 1, 2021. Relative risk was calculated using bilateral association measures (exact fisher, mid-p or chi-squared tests, as appropriate) to compare the incidence of infection and hospitalization of SCD patients to the population of Quebec and to assess risk factors of hospitalization among SCD patients. Results During the first 12 months of the pandemic, 74 patients were included in the registry. The male to female ratio was 1:1.12. Median age was 23 years, ranging from 8 months to 68 years old. SS-Sbeta 0 genotypes were present in 51% of cases, while 49% were SC or Sbeta +. The majority of patients were on disease modifying therapy: 54% were on hydroxyurea and 17.5% on exchange transfusion therapy. The incidence of reported COVID-19 infection was significantly higher in SCD patients compared to the general population (4.9% vs. 3.5% p=0,002) (Table 1). Even more strikingly, SCD had rate of hospitalization 10-times greater than the general population (33.8 vs 3.2%, p&lt;0,001). Nevertheless, the risk of admission to the intensive care unit was similar between SCD patients and the general population (24.0% vs. 24.1%, p=0.99). No death was recorded amongst SCD patients with COVID-19 compared to a death rate in the general population in Quebec of less than 70 years old of 48-78 for 100 000 infections (male-female). A history of acute chest syndrome (ACS) in the last year (OR 2.6 [1.5-4.6], p=0.04) and arterial hypertension (OR 3.3 [2.3-4.8], p=0.01) were associated with a higher risk of hospitalization (Table 2). On the other hand, there was no statistically significant association with age, sex, genotype, ABO blood group, baseline SCD therapy, or other comorbidities (chronic renal disease, obesity, pulmonary hypertension, chronic lung disease and previous admission to ICU) in our cohort. Conclusions Similar to other reports, we found that SCD patients were at much greater risk of hospitalization compared to the general population. We however found no increased risk of mortality or disease complication. This contrasts with results from other registries. A history of ACS and hypertension were associated with a higher risk of hospitalization. Whether social determinants of health could explain some of the outcome variability between different countries merit further investigation. Furthermore, we believe that registries are critical to monitor the impact of preventive measures. As vaccination is ongoing, it will be important to consider its impact on hospitalization and death rate among SCD population. Recruitment to the registry is ongoing and updated data will be presented at the meeting. Figure 1 Figure 1. Disclosures Soulieres: BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding. Forté: Novartis: Honoraria; Canadian Hematology Society: Research Funding; Pfizer: Research Funding.

Lead Neuropathy and Sickle Cell Disease

PEDIATRICS ◽  
1974 ◽  
Vol 54 (4) ◽  
pp. 438-441
Author(s):  
Gerald Erenberg ◽  
Steven S. Rinsler ◽  
Bernard G. Fish
Keyword(s):  
Case Report ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Lead Poisoning ◽  
Cell Disease ◽  
Hemoglobin S ◽  
Increased Risk ◽  
Rare Manifestation ◽  
Poisoning In Children

Four cases of lead neuropathy in children with hemoglobin S-S or S-C disease are reported. Neuropathy is a rare manifestation of lead poisoning in children, and only ten other cases have been well documented in the pediatric literature. The last previous case report of lead neuropathy was also in a child with hemoglobin S-S disease. The neuropathy seen in the children with sickle cell disease was clinically similar to that seen in the previously reported cases in nonsicklers, but differed in both groups from that usually seen in adult cases. It is, therefore, postulated that children with sickle cell disease have an increased risk of developing neuropathy with exposure to lead. The exact mechanism for this association remains unknown, but in children with sickle cell disease presenting with symptoms or signs of peripheral weakness, the possibility of lead poisoning must be considered.

scholarly journals A case of severe multi-system disease in a sickle cell SC patient caused by parvovirus B19 infection

2021 ◽  
Vol 2 (5) ◽  
Author(s):  
Mohamed Almuqamam ◽  
◽  
Swetha Madhavarapu ◽  
Nataly Apollonsky ◽  
◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Parvovirus B19 ◽  
Acute Infection ◽  
Organ Injury ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Splenic Sequestration ◽  
Increased Risk ◽  
Parvovirus B19 Infection

Sickle Cell Disease (SCD) is an inherited hemoglobinopathy, which results in production of abnormal hemoglobin S. HbSC disease is a variant of SCD, which shares a similar clinical complication profile to HbSS disease, but often thought to be a milder condition. In patients with SCD, Hb S in deoxygenated state undergoes polymerization, leading to hemolysis, vaso-occlusive events, and eventually end-organ damage. Among other complications in patients with SCD is increased risk of complications caused by parvovirus B19. We present a case of a 14-year-old female with HbSC disease who presented to the emergency room with complaint of abdominal pain and found to have splenic sequestration. Splenic sequestration progressed rapidly, Hemoglobin (hb) dropped to 4.6 g/dl and acute chest syndrome (ACS) developed. She was treated following the ACS protocol, received 4 units of Packed Red Blood Cells (PRBC) and subsequently underwent a single volume PRBC exchange transfusion. Considering her unusual presentation, with severe ARDS from alveolar hemorrhage requiring mechanical ventilation and multi-organ injury, several autoimmune and infectious conditions with a cytokine storm component including COVID-19 disease, were considered. Results of viral testing revealed parvovirus B19 IgM antibodies signifying an acute infection. She fully recovered with supportive care and was discharged home. Multisystem involvement simulating connective tissue disorders or malignancies with acute parvovirus B19 infection has been reported and is considered extremely rare. To our knowledge, there were no reports of pediatric patients with SC disease presenting with splenic sequestration and ACS in the setting of parvovirus B19 multisystem disease. Keywords: sickle cell disease; acute respiratory distress syndrome; acute chest syndrome; parvovirus B19.

scholarly journals COVID Symptoms and COVID Anxiety in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Wally R Smith ◽  
Benjamin Jaworowski ◽  
Shirley Johnson ◽  
Thokozeni Lipato ◽  
Daniel M Sop
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Telephone Survey ◽  
Cell Disease ◽  
Weighted Mean ◽  
The Us ◽  
Associated Symptoms ◽  
At Home

Background Even before the US upswing of the current COVID pandemic, the number of sickle cell disease (SCD) patients coming to hospitals and EDs appeared to fall drastically. This happened despite SCD patients having often been heavy utilizers of the ED and hospital for their iconic vaso-occlusive crises (VOC). Though ambulatory SCD clinics quick converted largely to telehealth in order to comply with stay-at-home orders designed to suppress person-to-person transmission, some SCD patients appeared to avoid care, delay care, or refuse doctors' invitations for care. Presumably patients did so out of COVID fears, but this has not been confirmed in the literature. Further, whether these patients had COVID symptoms but stayed at home has not been studied. As part of quality improvement (QI) to conduct COVID surveillance in an adult sickle cell program, we sought to explain and predict SCD health care utilization patterns we were observing, as well as to determine urgent physical and mental health needs of patients who appeared to be avoiding care. Methods Fifteen staff in the Adult Sickle Cell Medical Home at Virginia Commonwealth University, a large urban academic medical center, conducted a telephone survey ("wellness check"was used when we talked to patients) of all known adults with SCD over 19 days in 2020. A staff member confirmed the patient had SCD, asked permission to proceed, then asked about symptoms consistent with COVID-19. At the end of the telephone survey, respondents wer invited to complete an email survey of sickle cell and COVID-19 utilization attitudes (19-33 items, depending on the response pattern, either drawn from the National Health Interview Survey, from the Adult Sickle Cell Quality of Life Measurement quality of care survey, or drafted by the authors), the Sickle Cell Stress Survey-Adult (SCSS-A, a 10-item previously validated survey), and anxiety and depression (PHQ9 of the PRIME-MD). Results Of 622 adults approached by phone call, 353 responded to the following yes/no screening questions regarding the prior 14 days: fever over 100 F 0/353 (0.00%); cough 3/353(0.01%); difficulty breathing 0/353(0.00%); unexplained shortness of breath 2/353(0.01%); sore throat 2/353 (0.01%); unexplained muscle soreness 2/353(0.01%);contact with anyone who tested positive for COVID-19 2/353(0.01%); testing for COVID 19 6/353(0.02%). For QI purposes, we set a threshold of three or more COVID-associated symptoms or the presence of fever as criteria requiring intense telephone or in-person staff monitoring for the following week. Only three patients met criteria. A total of 219/353 had email surveys sent. Of 63 patients (28.8%) who returned email surveys by June 10, 2020, 35.9% had already managed a "pain attack" at home 4 or more times in the prior 12 months, and 45.5% of these said their bad ER experiences were very or somewhat important in that decision. In the prior 14 days, although 30/64 reported a crisis for at least one day, only 4/64 had visited the Emergency Department for pain. On a 0-10 scale, 21/61 patients endorsed "0" for worry that they would be COVID-infected by going for medical care (weighted mean 3.9), but 18/59 endorsed "10" for worry they were more at risk of COVID because of SCD (weighted mean 6.31), and 22/60 endorsed "10" for worry they would fare worse than others if COVID infected (weighted mean 6.97). Many patients forwent "needed" care (16/62) or delayed "needed" care by at least a day (36/61). Eleven patients met criteria for moderately severe to severe depression on the PHQ-9, and 28/63 somewhat or strongly agreed with the statement "death is always on the back of my mind" on the SCSS-A. Conclusions In adolescents and adults with SCD, many were already reticent to come to the ED for pain, but a significant portion reported delays or avoidance of needed care during the early stages of the US COVID pandemic, and few reported using the ED despite over half reporting at least one crisis day in 14. Patients nonetheless reported very few COVID-associated symptoms. Fears of COVID infection/susceptibility may limit visits for needed sickle cell care among adults. Acknowledgements: Mica Ferlis RN, FNP, Caitlin McManus, RN, FNP, Emily Sushko, RN, FNP, Justin West, RN, Kate Osborne, RN, Stefani Vaughan-Sams, Marla Brannon, BS, Nakeiya Williams, BS Disclosures Smith: GlycoMimetics, Inc.: Consultancy; Emmaeus Pharmaceuticals, Inc.: Consultancy; Novartis, Inc.: Consultancy, Other: Investigator, Research Funding; Global Blood Therapeutics, Inc.: Consultancy, Research Funding; Shire, Inc.: Other: Investigator, Research Funding; NHLBI: Research Funding; Patient-Centered Outcomes Research Institute: Other: Investigator, Research Funding; Health Resources and Services Administration: Other: Investigator, Research Funding; Incyte: Other: Investigator; Pfizer: Consultancy; Ironwood: Consultancy; Novo Nordisk: Consultancy; Imara: Research Funding; Shire: Research Funding.

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