Ischemic stroke is a devastating complication of sickle cell anemia (SCA) and can affect children from a very young age. It is the commonest cause of stroke in the general pediatric population. The ...peak incidence is in the first decade of life and approaches 11% in the absence of stroke prevention programmes. The advent of transcranial doppler (TCD) screening as part of a primary stroke prevention programme has reduced the incidence of stroke by 90%. However, not all strokes are prevented by TCD, and TCD abnormalities are not specific, with up to 60% children receiving transfusions unnecessarily. Understanding the underlying pathophysiology of cerebrovasculopathy in SCA and recognition of important risk factors will lead to a more stringent identification of the at-risk population.
Analysis of siblings with stroke and abnormal TCDs offers good evidence that a proportion of this variability is conferred by inherited genetic variation. Identifying those specific variants has proved elusive, with many conflicting findings reported in the literature, no doubt reflecting the limited power of many studies to address the complex overlay of environmental and genetic influences. To attempt to minimise the impact of non-genetic confounders, our study looked specifically at children who had an overt ischemic stroke or developed abnormal TCD measurements (TAMMV >200cm/s) prior to their 4th birthday, in the absence of potentially precipitating acute medical events.
We recruited 22 patients, 19 of whom had an ischemic stroke, and 3 who developed abnormal TCD measurements, prior to 4 yrs of age. Additionally, we recruited the dizygotic twin of one stroke case, who had SCA, but, importantly, no cerebrovascular complications, as confirmed by MRI/A aged 15 yrs. We extracted DNA from peripheral blood samples. Exome library was prepared using Agilent SureSelect XT V7, sequencing was performed using Illumina NovaSeq. Alignment, assembly, variant calling and annotation were based on a GATK Best Practices workflow. For each sample, around 15000 non-synonymous variants were identified. Across the 22 case samples, 58 variants in 56 genes were predicted to be pathogenic or likely pathogenic, as determined with InterVar. These variants were interpreted with respect to dbSNP documentation and biological role of the gene they affected. Variant segregation within the twin pair was also considered.
Two patients were homozygous for rs429358, a missense variant in the APOE gene that is pathogenic for familial hyperlipoproteinemia, type 3. Moreover, 3 further patients were compound heterozygous for this variant plus another APOE missense variant pathogenic for the same condition, rs7412. One of these 3 cases was the affected sibling of the twin pair and notably, the unaffected twin carried only heterozygous rs429358 and not rs7412. A further patient was heterozygous for rs121908043 in the LDL-R gene, which is pathogenic of Familial Hypercholesterolaemia, even in the heterozygous state. Finally, in an additional patient, we identified a potential compound heterozygote of a known pathogenic variant, rs118204068 with another missense variant rs11542065 in the LPL gene, to cause Hyperlipoproteinemia type 1.
We have used whole exome sequencing to analyse patients with sickle cell anemia and stroke at a very young age, an extreme phenotype, in whom we predicted genetic factors would be a significant cause of stroke. We found 7 of the 22 patients (32%) had variants diagnostic of inherited dysplipidaemias, including 5 with familial hyperlipoproteinemia type 3, 1 with hyperlipoproteinemia type 1 and one with familial hypercholesterolemia. Our analysis included one twin set and it is noteworthy that the unaffected twin sibling did not carry the necessary variants defining the inherited dyslipidaemia. These conditions are characterised by improper breakdown and accumulation of LDL-C, triglycerides and cholesterol, which has been associated with vascular dysfunction and hemolysis in SCA and are strongly associated with stroke and cardiovascular disease in the general population. This is potentially an important finding that warrants further investigation into the role of lipids and hyperlipidemia in the development of stroke and cerebral vasculopathy in the sickle cell population. In the long term, we suggest that measurement, and potentially, control of lipids may form a component of the primary stroke prevention programme.
Brousse:Add medica: Consultancy; bluebird bio: Consultancy. Rees:Novartis: Other: Strategic advisory role,Principal investigator,sickle cell disease2.6 Investigator; Astra Zeneca (ticagrelor): Other: Data monitoring committees; TauRx (methylene blue): Other: Data monitoring committees; Alnylam: Other: Principal investigator; Global Blood Therapeutics: Other: Strategic advisory role; Celgene: Other: Strategic advisory role; Emmaus: Other: Strategic advisory role; Agios: Other: Grants.
Low hemoglobin (Hb) level at steady state in subjects with sickle cell anemia (SCA) may indicate severe chronic hemolysis and might be related to a more severe course of disease.
In this study we ...investigated the hypothesis that low hemoglobin at steady state may be associated with higher rate of lung function impairment in children and adolescents with SCA.
Methods
In this cross-sectional study black African subjects with SCA (Hb phenotype SS) aged 6 to 18 years followed at the Barau Dikko Teaching Hospital, Kaduna, Nigeria, underwent spirometry and anthropometry measures. A recent Hemoglobin level at steady state was recorded for each patient. Caregivers or patients were interviewed through a questionnaire investigating a history of asthma or acute chest syndrome (ACS) and frequency of pain crises in the last year that required analgesics for at least 24 hours. Exclusion criteria were: the lack of recorded complete blood count (CBC) performed in the last 6 months, respiratory symptoms or feeling unwell on the test day, SCA-related acute events (e.g., pain crises) in the last two weeks or a blood transfusion or an ACS episode in the last month. A portable Easy-on-PC spirometer (ndd, Zurich, Switzerland) was used. Data were included if at least two forced expiratory manoeuvres met the ATS/ERS acceptability and repeatability criteria adapted for children (Miller MR, ERJ 2005; Kirkby J, Pediatr.Pulmonol.2008). Spirometry z-scores and percentage of predicted for FEV1, FVC and FEV1/FVC were derived according to the GLI-2012 reference equations for African Americans (Quanjer PH, ERJ2012). Spirometry patterns were classified as normal, obstructive (zFVC ≥ 1.64 + zFEV1/FVC < -1.64), restrictive (zFVC < -1.64 + zFEV1/FVC ≥ -1.64) or mixed (zFVC < -1.64 + zFEV1/FVC < -1.64) and a FEV1 < 70% of predicted was considered indicative of lung end-organ disease (Kassim AA et al, Blood. 2015 Sep 24;126(13):1544-50). Group comparison between patients with Hb level < 7.5 g/dL versus Hb ≥7.5 g/dL were tested using unpaired t test, χ2 or Fisher's exact test as appropriate. The relationship between Hb values and spirometry outcomes was explored through logistic and linear regression models. P-value < 0.05 was adopted as representing a statistically significant difference. Analyses were conducted using the software STATA and Graphpad Prism 7.
Results
A total of 186 subjects with SCA were initially enrolled. Only one child was on hydroxyurea. After exclusions, data from 126 patients (mean ± SD age of 11.5 ± 3.1 yr., 53% boys) were retained for the final analysis. Mean ± SD Hb value was 7.8±0.9 g/dL (range 5.6 to 10.9). Frequency of low Hb (< 7.5 g/dL) at steady state was 30.9% (39/126).
Mean FEV1 and FVC z-scores were lower and frequency of FEV1 < 70% of predicted was higher in patients in the low Hb group compared to those with Hb ≥7.5 g/dL though differences were not statistically significant (table 1). Prevalence of restrictive spirometry pattern, possibly suggesting restrictive lung disease, was significant higher in patients with Hb level < 7.5 g/dL (17/39, 43.5%) than in those with Hb ≥7.5 g/dL (20/87, 22.9%) (p = 0.01; table 1).
The odds ratio for restrictive spirometry pattern in presence of Hb level <7.5 g/dL was 2.5 (95% CI 1.1 to 5.7; p = 0.03). In a linear regression model (figure 1) the FVC z-score resulted significantly related to the Hb level with an increase of 0.17 z-scores for each point of Hb (95% CI 0.01 to 0.34, p = 0.04; R2 = 0.03).
Frequency of asthma, pain crises and previous acute chest syndrome did was similar between the two groups (data not showed)
Conclusions
In Nigerian pediatric patients with sickle cell anemia a hemoglobin level < 7.5 g/dL at steady state was associated with a 2.5 higher risk of presenting a restrictive spirometry pattern and with a higher frequency of end-organ lung disease (FEV1 < 70% of predicted). Low hemoglobin levels in wellbeing may depend on intense chronic haemolysis that could worsen microangiopathy, inflammation and ischemia and reperfusion injury in the lungs, potentially determining a precocious onset of restrictive lung disease.
These preliminary data seem to indicate that a low Hb level at steady state in African pediatric patients with sickle cell anemia is associated with more severe lung impairment and should prompt respiratory assessment with lung function when found.
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Inusa:Novartis plc: Honoraria, Research Funding, Speakers Bureau; Astrazeneca: Consultancy.
Sickle cell disease (SCD) is now the most common genetic condition in the world including the UK with an estimate of over 12,500 affected people and over 300 new births per year. Blood transfusion ...therapy plays a very important role as a disease-modifying strategy in severe SCD e.g. primary and secondary stroke prevention and other acute life-threatening complications such as acute chest infections and acute multi-organ failure. Blood transfusion, however, carries a number of risks including alloimmunisation. There is the need to increase the level of awareness and education about SCD and also to increase blood donation drive among affected communities. These communities are mostly ethnic minority populations who are recognised to have poor access to health care services. Due to the strong impact of religion on these populations, faith organisations may provide potential access for health promotion and interventions.
A literature search was conducted to find studies published between 1990-2008 aimed at examining the influence of religious leaders and faith organisations in health, with particular reference to haemoglobinopathies.
Eleven studies were reviewed covering a variety of health interventions. The findings suggest that involvement of religious leaders and faith organisations in health related interventions improved the level of acceptance, participation and positive health outcomes within the faith communities.
Religious leaders and faith organisations have the potential to influence health education, health promotion and positive health outcomes amongst members of their faith community. They also provide potential access to at-risk populations for increasing awareness about SCD, encouraging health service utilization and ethnic blood donor drives.
Background: There is a significant unmet need for treatments to reduce vaso-occlusive crises (VOCs) in sickle cell disease (SCD). Until recently, the only pharmacological treatment approved for ...reduction of VOCs was hydroxyurea (hydroxycarbamide), and is recommended for children ≥9 months old with SCD. L-glutamine is approved for the reduction of acute complications of SCD in children ≥5 years old, although symptoms can start as early as 5 months of age. Inhibition of platelet activation has been proposed as a potential therapeutic option for SCD. The rationale for the use of antiplatelet therapies in SCD management is based on evidence that platelets participate in the vaso-occlusive process and that platelet activation correlates with the frequency of pain episodes (Ataga et al, 2012). Platelets are activated during the non-crisis steady state (Lee et al, 2006). The antiplatelet drug ticlopidine, which has a similar mechanism of action as ticagrelor (prevention of adenosine diphosphate ADP-mediated platelet activation), significantly reduced the frequency of VOCs in patients with SCD (Cabannes et al, 1984). In the phase III DOVE study in pediatric patients, the platelet inhibitor prasugrel was shown to result in a numerical reduction in VOC events with fewer painful crises in the prasugrel group (66%) versus placebo (72%); however, the differences versus placebo did not reach statistical significance (Heeney et al, 2016). Of note is that the prasugrel doses used in DOVE only resulted in a mean platelet inhibition of ~20% (Jakubowski et al, 2017). The low platelet inhibition may have contributed to the lack of efficacy in this study (Heeney et al, 2016). Ticagrelor is an oral, direct-acting, selective, reversibly-binding P2Y12 receptor antagonist that prevents ADP-mediated platelet activation and aggregation. Ticagrelor was approved in 2010 to reduce the rate of cardiovascular death, myocardial infarction, and stroke in adult patients with acute coronary syndromes, and is currently approved in >100 countries. A program is currently ongoing to assess the potential therapeutic benefits of ticagrelor in reducing the occurrence of VOCs in children with SCD. A phase III study (HESTIA3; NCT03615924) is underway to evaluate the efficacy of ticagrelor in reducing the rate of VOCs, as well as the safety and tolerability of ticagrelor versus placebo in SCD pediatric patients 2 to <18 years old. The present phase 1 study (HESTIA4; NCT03492931) was conducted to investigate whether ticagrelor exposure in children <24 months old is similar to that in older children. Thus, the primary objective of HESTIA4 was to determine the pharmacokinetic (PK) properties of ticagrelor in children with SCD aged 0 to <24 months after a single oral dose. This study will enable selection of an appropriate dose for further evaluation of the effect of ticagrelor in preventing VOCs in children <24 months.
Methods: Twenty-one children aged 3-21 months with SCD were given a single, oral dose of ticagrelor (0.1 mg/kg for the age group <6 months and 0.2 mg/kg for the age group ≥6 months.). Four PK blood samples were collected i.e. at 1, 2, 4 and 6 hours post dose from each patient. A follow-up visit was conducted between days 4 to 8 post-dosing. For dose selection in HESTIA4, a pediatric physiologically-based PK model was developed based on physiochemical, in vitro and final PK data from children 2 to <18 years in HESTIA1 (NCT02214121). This model was used to predict ticagrelor exposure in children in the age groups 0 to <6, 6 to <12 and 12 to <24 months. The proposed doses in HESTIA4 were selected for the detection of ticagrelor and active metabolite in plasma after a single dose without causing a pronounced degree of platelet inhibition.
Results: There were no bleeding events reported, and there was only one serious adverse event reported (hospitalization due to bronchiolitis 7 days after dosing, considered not related to ticagrelor). The results show that ticagrelor PK, with weight-based dosing, results in comparable exposure in children aged 0 to <6, 6 to <12 and 12 to <24 months, and that exposure was similar to children aged >24 months.
Conclusion: The present PK results with ticagrelor show a good correlation between predicted and observed exposure, supporting the evaluation of ticagrelor in children with SCD <24 months of age using weight-based dosing. Single-dose ticagrelor, at the doses evaluated, was well tolerated in this population.
Inati:Global Blood Therapeutics: Research Funding; AstraZeneca: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novonordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Githanga:AstraZeneca: Other: Member of the steering committee in phase III study in Brilinta Pediatric Program. Abboud:AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eli Lilly: Research Funding; Modus: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Other: Travel support; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; CRSPR Therapeutics: Membership on an entity's Board of Directors or advisory committees; GBT: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cela:Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Not personal, but on behlalf of the Spanish Pediatric Hematology Society) Funding for the Spanish Hemoglobinopathy registry . Niazi:AstraZeneca: Employment, Equity Ownership. Åstrand:AstraZeneca: Employment. Persson:AstraZeneca: Employment. Berggren:AstraZeneca: Employment. Carlson:AstraZeneca: Employment, Equity Ownership.
Ticagrelor is a P2Y12 platelet inhibitor indicated to reduce the rate of cardiovascular death, myocardial infarction (MI) and stroke in patients with acute coronary syndrome (ACS) or a history of MI. The current study in the submitted abstract is a phase 1 study to characterize the pharmacokinetic and safety profiles of ticagrelor in infants and toddlers aged less than 24 months, with sickle cell disease.
This article reviews data about transition from paediatric to adult services in patients with sickle cell disease, the most common inherited disease in the UK, and outlines how this has been ...addressed in a large UK sickle cell centre.
Background: Sickle cell disease (SCD) is a complex genetic disorder affecting mainly people of African origin. A hallmark of SCD is vaso-occlusive crisis (VOC) - this event is acutely painful and the ...primary cause of hospitalization in SCD patients. VOC can lead to life-threatening complications such as acute chest syndrome. SCD is also associated with chronic complications including pulmonary hypertension, damage to organs and shortened life expectancy. Therefore, effective management and treatment strategies are essential to reduce burden of illness and ensure high quality of life for the patient.
Aim: To survey the treatment and management strategies used by patients with SCD, and to determine patient satisfaction levels.
Methods: SWAY is an ongoing multi-country, cross-sectional survey of SCD patients, caregivers and treating physicians. The survey, conducted online and in print, includes 6 categories: demographics, symptoms, impact of disease and use of a caregiver, impact on work and finances, disease management/treatment approaches, and patient-physician relationship. Where relevant, questions include a 7-point severity scale for each statement; a score of 5−7 indicates ‘high severity/impact’. Patient enrollment is via treating physicians and patient association groups. The enrollment target is approximately 2000 patients.
Results: To date, 1513 SCD patients (48% male, mean age 24.1 years, 63% HbSS and 30% HbSC disease) have been surveyed from 11 countries across North and South America, Europe and Africa. When considering the main person responsible for SCD treatment and management, patients primarily reported management by an SCD specialist (59% of patients) or GP/family doctor (20%). Most patients were satisfied with the frequency of interaction with their doctor (78%) and reported they are confident they are being assessed and treated properly (66%; based on high-impact scores 5−7). Accordingly, 60% of patients (scoring 5−7) reported sharing the same goals for SCD management and treatment as their doctor. The most common treatment goals for patients are to improve quality of life (80% of patients), prevent SCD worsening (59%), improve long-term survival (42%) and improve overall symptoms (40%). Patients reported receiving ongoing treatment with folic acid (58%), antibiotics (37%), anti-inflammatories (37%), over-the-counter pain medication (37%), opioids (35%), hydroxyurea (23%), blood transfusions (10%) and L-glutamine (4%). Having surgery or a medical procedure to manage their SCD was reported by 47% of patients, with gall bladder removal (16%), port placement (15%) and splenectomy (11%) being the most frequent. Although 63% of patients (scoring 5−7) indicated satisfaction with their treatment received to manage their SCD, 75% of patients (scoring 5−7) agreed they would like an alternative treatment to their current pain management medication, and 67% of patients would like additional professional emotional support.
In the 12 months before survey completion, 7829 VOCs were reported (mean of 5.2 VOCs per patient); 8% of patients experienced 0 VOCs, 51% experienced 1−4 VOCs and 40% experienced ≥5 VOCs. Of these, 38% of VOCs led to overnight hospitalization, 24% were managed at home and 19% were treated in the emergency room. The main reasons that patients chose to manage their VOCs at home include a previous poor experience at hospital (40%), the opinion that medical assistance was not required (28%), the perception that medical professionals do not understand SCD (27%) and the cost of hospital treatment (22%; 41% of patients have no health insurance). Patients who self-managed their VOCs primarily did so with rest/sleep (73%), by drinking fluids (72%) and with opioid-based analgesia (58%).
Conclusions: This interim analysis of the SWAY survey suggests that although many patients report satisfaction with their current level of management and treatment, there is still a need for additional healthcare support and alternative treatments. Underlining this, many patients experiencing VOCs do not seek medical assistance despite the potential for life-threatening complications, and >75% of patients surveyed are not receiving hydroxyurea even though the majority are cared for by SCD specialists. Further data collection and analysis will highlight any geographic differences in SCD management strategies and help identify any region-specific unmet patient needs.
James:Novartis: Honoraria; Sickle Cell Society: Employment. Andemariam:NovoNordisk: Membership on an entity's Board of Directors or advisory committees; New Health Sciences: Membership on an entity's Board of Directors or advisory committees; Emmaus: Membership on an entity's Board of Directors or advisory committees; Cyclerion: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Imara: Research Funding; Global Blood Therapeutics: Other: DSMB Member; Community Health Network of Connecticut: Consultancy; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Membership on an entity's Board of Directors or advisory committees. El-Rassi:Novartis Pharmaceuticals: Research Funding. Francis-Gibson:Sickle Cell Disease Association of America: Employment. Nero:Novartis: Consultancy. Minniti:Doris Duke Foundation: Research Funding. Trimnell:Novartis: Consultancy; Global Blood Therapeutics: Consultancy; Cyclerion: Consultancy. Abboud:Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Modus: Research Funding; CRSPR Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Other: Travel support; Eli Lilly: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; GBT: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Colombatti:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees. de Montalembert:AddMedica: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Jastaniah:Novartis: Consultancy, Honoraria. Nur:Novartis: Consultancy. DeBonnett:Novartis Pharmaceuticals Corporation: Employment. Osunkwo:Micella Biopharma: Other: DSMB Member ; Terumo: Speakers Bureau; Pfizer: Consultancy; Novartis: Consultancy, Speakers Bureau.
Background: Sickle cell disease (SCD) is a multi-system disease affecting millions of people. The disease is characterized by vaso-occlusive crises (VOCs), resulting in acute and chronic pain, ...end-organ damage and life-threatening complications. The symptoms experienced by patients, caused largely by multi-cellular adhesion leading to vaso-occlusion and vasculopathy, significantly affect their quality of life (QoL) and ability to work/study. Understanding the effect of SCD on patients' daily lives can inform management of the disease and improve patients' QoL.
Aims: To assess the impact of SCD on patients' daily lives, including physical symptoms, emotional wellbeing and economic burden, based on the worldwide SWAY survey.
Methods: SWAY is an ongoing multi-country, cross-sectional survey of SCD patients, caregivers and treating physicians. Data are collected using self-completed or proxy surveys and categories include demographics, symptoms and impact of disease (physical, emotional and financial) and need for a caregiver. Where relevant, questions include a 7-point severity scale for each statement, with a score of 5 to 7 indicating ‘high severity/impact’. Patient enrollment is via treating physicians and patient association groups. The enrollment target is approximately 2000 patients.
Results: To date, 1513 SCD patients (48% male, mean age 24.1 years, 63% HbSS and 30% SC disease) have been surveyed from countries across the world, including the USA (365), UK (299), Nigeria (264), Ghana (255), Brazil (160) and Germany (91). The most commonly experienced symptoms of SCD were bone aches (63%), difficulty concentrating (49%), difficulty gaining weight (49%) and joint stiffness (41%). For these symptoms, 67%, 53%, 70% and 59% of patients rated them as ‘high severity’ on the 7-point scale, respectively. Background pain was present on an average of 2.9 days per week (standard deviation SD=2.2). Commonly experienced complications of SCD include fever (65%), joint issues (55%) and infections (55%). Patients reported a total of 7829 VOCs, with a mean of 5.2 VOCs per patient (SD=5.07) in the 12 months before survey completion; 38% of these VOCs resulted in overnight hospitalization, 24% were managed at home, 19% were treated in the emergency room and 19% of patients sought medical assistance in the community.
A high impact on emotional wellbeing was reported by 61% of patients. The highest impact was caused by frustration with symptoms (60%), worry about disease worsening (59%) and worry about family/friends/children who care for them (54%). Only 42% of patients have received professional emotional support (eg psychiatrist, psychologist, counseling), but 67% reported a desire to receive this support.
A high impact on household daily activities (eg food preparation, housework, childcare) and on family or social life was reported by 39% and 43% of patients, respectively, with 34% stating a high impact in terms of sexual desire/activity and 35% a high impact on relationships with spouse/partner. Physical activity was also affected in patients with SCD, with 60% reporting they avoid intense physical activity and 30% avoiding even mild physical activity, most commonly because of concerns about pain, exhaustion and dehydration (58%, 57% and 50%, respectively).
Of the patients surveyed, 32% were employed, 8% not working but seeking employment, 6% not working and not seeking employment, 36% students, 1% retired, 13% on disability pay and 1% long-term sick leave. Employed patients reported SCD had a high impact on their ability to work, with 57% reducing their hours and 47% considering leaving their job. An average of 6.3 hours missed from work was reported in the 7 days prior to survey completion due to SCD. Half of patients believe that their income would be higher if they did not have SCD, 60% reported often missing school in the past and 52% felt that their disease has had a negative impact on their academic achievements.
Conclusions: The acute and chronic symptoms associated with SCD have a substantial impact on patients' daily lives, including emotional and physical wellbeing, relationships and school/work. In addition, the acute symptoms associated with VOCs occur several times a year, resulting in frequent hospitalizations. Improved management of SCD would enhance patients' quality of life both at home and at school/work, likely leading to improved emotional wellbeing and a positive economic effect.
Osunkwo:Micella Biopharma: Other: DSMB Member ; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy; Terumo: Speakers Bureau. Andemariam:Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Other: DSMB Member; Imara: Research Funding; NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Membership on an entity's Board of Directors or advisory committees; Cyclerion: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Emmaus: Membership on an entity's Board of Directors or advisory committees; New Health Sciences: Membership on an entity's Board of Directors or advisory committees; Community Health Network of Connecticut: Consultancy. El-Rassi:Novartis Pharmaceuticals: Research Funding. Francis-Gibson:Sickle Cell Disease Association of America: Employment. Nero:Novartis: Consultancy. Minniti:Doris Duke Foundation: Research Funding. Trimnell:Global Blood Therapeutics: Consultancy; Novartis: Consultancy; Cyclerion: Consultancy. Abboud:AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; CRSPR Therapeutics: Membership on an entity's Board of Directors or advisory committees; Modus: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Eli Lilly: Research Funding; GBT: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Other: Travel support; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Colombatti:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees. de Montalembert:AddMedica: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Jastaniah:Novartis Pharmaceuticals: Consultancy, Honoraria. Nur:Novartis Pharmaceuticals: Consultancy. DeBonnett:Novartis Pharmaceuticals Corporation: Employment. James:Sickle Cell Society: Employment; Novartis: Honoraria.
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