Adult Sickle Cell Disease Population Research Articles

The enigma of sickle cell hepatopathy: Pathophysiology, clinical manifestations and therapy.

Sickle cell disease (SCD) is one of the most common genetic disorders in the world predominantly affecting economically disadvantaged populations. There is a notable discrepancy between the growing adult SCD population and available diagnostic and therapeutic interventions for SCD. Sickle cell hepatopathy (SCH) is an all-inclusive term to describe the acute and chronic liver manifestations of SCD. The pathophysiology of SCH follows no defined pattern or sequence that poses challenges to clinicians and researchers alike. Evidence is lacking for this underreported disease at various levels from diagnostic to therapeutic options. This paper reviews the basic pathophysiology, clinical features, biochemical and radiological findings of various SCH manifestations and outlines the management of each condition. Old and new therapy options in SCD including hydroxyurea, red blood cell exchange transfusion, ursodeoxycholic acid, voxelotor, l-glutamine and crizanlizumab have been reviewed to investigate the role of these options in treating SCH. The role of liver transplant, haematopoietic stem cell transplant and gene therapy in SCH patients have been reviewed.

Diagnostic Test Accuracy of Lung Ultrasound for Acute Chest Syndrome in Sickle Cell Disease: A Systematic Review and Meta-analysis

Acute chest syndrome (ACS) is a leading cause of death in patients with sickle cell disease. Lung ultrasound (LUS) is emerging as a point-of-care method to diagnose ACS, allowing for more rapid diagnosis in the ED setting and sparing patients from ionizing radiation exposure. What is the diagnostic accuracy of LUS for ACS diagnosis, using the current reference standard of chest radiography? Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed for this systematic review and meta-analysis. Embase, MEDLINE, Web of Science, and Google Scholar were used to compile all relevant studies. Two reviewers screened the studies for inclusion in this review. Cases of discrepancy were resolved by a third reviewer. Meta-analyses were conducted using both metadta and midas STATA software packages to retrieve summary receiver operating characteristic curves, sensitivities, and specificities. Three reviewers scored the studies with QUADAS-2 for risk of bias assessment. From a total of 713 unique studies retrieved, six studies were included in the final quantitative synthesis. Of these, five studies were in pediatric EDs. Two studies were conference abstracts and not published manuscripts. Data were available for 625 possible ACS cases (97%of cases in patients aged≤ 21 years) and 95 confirmed ACS diagnoses (pretest probability of 15.2%). The summary sensitivity was 0.92 (95%CI, 0.68-0.98) and the summary specificity was 0.89 (95%CI, 0.69-0.97) with an area under the curve of the summary receiver operating characteristic curve of 0.96 (95%CI, 0.94-0.97). LUS has excellent sensitivity and very good specificity for ACS diagnosis and may serve as an initial point-of-care test to facilitate rapid treatment of ACS and spare pediatric patients from ionizing radiation; however, further research is warranted to improve the generalizability to the adult sickle cell disease population.

Characterising the prevalence of overweight and obese status among adults with sickle cell disease.

Individuals with sickle cell disease (SCD) have historically been considered underweight. Despite increasing body mass index (BMI) in the general population, the prevalence of overweight and obese status remains unclear in the adult SCD population. Our primary aim was to determine the prevalence of overweight and obese status and to identify associations between BMI, demographic, and clinical characteristics. We conducted an analysis of abstracted electronic health record data and patient-reported outcomes from the Sickle Cell Disease Implementation Consortium registry; individuals aged 20-45 years were included. The median (interquartile range) BMI for the 1664 adults in this analysis was 23.9(21.1-28)kg/m2 . In this cohort, 42.9% had a BMI of >25 kg/m2 (Centers for Disease Control and Prevention definition of overweight/obese). In multivariable analysis, higher odds of being overweight or obese were associated with female gender, older age, college education, private insurance, and hypertension diagnosis. Higher odds of a BMI of >25 kg/m2 were observed in individuals with HbSC or HbSβ+ thalassaemia regardless of hydroxycarbamide (hydroxyurea) exposure (odds ratio [OR] 3.4, p < 0.0001) and HbSS or HbSβ0 thalassaemia exposed to hydroxycarbamide (OR 1.6, p=0.0003) compared to those with HbSS or HbSβ0 thalassaemia with no hydroxycarbamide exposure. These data highlight the importance of early identification, prevention, and intervention for increasing BMI to reduce obesity-related complications that may impact SCD-related complications.

Transfusional Iron Overload in Sickle Cell Patients:Outcomes of Chelation Therapy

Iron (Fe) overload is not rare among sickle cell disease (SCD) patients. It results from either chronic transfusions for primary or secondary stroke prevention, or more commonly sporadic, mostly unnecessary transfusions and are associated with significant morbidity, secondary to hepatic, cardiac and renal Fe deposition. Previous studies at our Center showed that 12% of the adult SCD population had Fe overload, and vast majority of these (80%) resulted from episodic transfusions (Son et al, 2013). Subsequent studies showed that the Fe regulatory peptide, hepcidin was appropriately upregulated in SCD subjects with Fe overload, and the plasma levels of the glycoprotein hormone erythroferrone (ERFE) was not as high as that found in patients with transfusion dependent beta thalassemia (TDT) due to the absence of significant ineffective erythropoiesis in SCD (Thawer et al, 2017, Mangaonkar et al, Brit. J. Haematol, 2020). We report on the utilization and outcomes in Fe overloaded SCD patients who were prescribed the oral chelating agent deferasirox.22 patients were prescribed deferasirox; median age was 38, 12 female 10 male. 21 had Hb SS, and 1 had s-b 0 thalassemia. Deferasirox dose ranged from 720-2500 mg/day (12 to 28 mg/Kg/day). Nonadherence was ascertained by patients' own admission. Figures 1-3 show the pre and post ferritin levels in subjects who were on deferasirox, and in controls; patients who took deferasirox had a more pronounced decrease in their ferritin (p=.004 vs p=.74). Although hepatic MRI for liver iron content (LIC) was not available on all patients, in those who underwent MRI there was a correlation between LIC and serum ferritin obtained at close temporal proximity (Fig. 4). Most common side effects of deferasirox were gastrointestinal (abdominal pain, nausea, vomiting, diarrhea), which were seen less commonly with the newer oral formulation (Jadenu).Several conclusions can be drawn from our observation on relatively small number of patients: 1) Deferasirox is effective in decreasing Fe overload as shown by serum ferritin levels 2) Second generation of oral deferasirox is better tolerated, and therefore is associated with improved adherence, 3) Documentation of a decrease in LIC with chelation will be important for the reversal of Fe induced organ damage, and 4) Parallel studies of the levels of Fe regulatory peptides hepcidin and erythroferrone (ERFE) will clarify the effect of chelation therapy on biomarkers of Fe metabolism. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Social support networks of adults with sickle cell disease.

Sickle cell disease (SCD) can cause both physical and psychological complications, such as severe pain and depression. These effects often necessitate social and caregiving support. Few studies have assessed support networks within the adult SCD population. Here, we describe the support networks of adults with SCD and identify who in these networks (1) provides emotional support, (2) is dependable during crisis situations, including social and financial adversities, and (3) provides assistance in health crises. Forty-nine adults with SCD completed surveys and social network assessments through interview. Generalized mixed-effects linear regression models were fitted to investigate the composition of support provision within these personal networks. Our findings indicate that parents and 'other important people' (e.g., friends, spouses) play key roles in the support provided to those with SCD. Siblings with SCD appeared to be more emotionally supportive than unaffected siblings. With much research centered around the pediatric and adolescent SCD populations, focus needs to extend to adults and the individuals involved in their care and disease management. Understanding the flow of support within these networks can help genetic counselors and healthcare providers to better identify both social ties that serve as support resources and less supportive relationships for individuals living with SCD and other chronic genetic conditions that might be targeted for intervention.

Psychoactive substance use disorders in an adult sickle cell disease population in Nigeria: prevalence and correlates

ABSTRACT Objective Pain conditions associated with Sickle Cell Disease (SCD) require alleviation with medications that may have potential for abuse. There is also an increased risk of abuse of non-prescription drugs. This study aims to assess the prevalence and correlates of substance use disorder (SUD) in an adult SCD cohort. Methods A cross-sectional study of an adult SCD cohort (n = 200) undertaking face-to-face interviews which utilized a socio-demographic questionnaire, the alcohol, and substance use disorder modules of the Mini International Neuropsychiatric Interview, the Pain Visual Analogue Scale, Measures of Sickle Cell Stigma and the Oslo Social Support Scale. Results Ten (5%) participants were diagnosed with a SUD, with a majority dependent on opioids. SUD was significantly associated with poor social support (p < .01), stigma (p < .01), but not perceived pain (p: ns), or physical comorbidity (p: ns). Conclusion A minority of persons with SCD were diagnosed with an SUD. Incorporation of prevention strategies focused on improved social support and minimizing stigma into routine care, may improve treatment outcomes and their quality of life.

The relationship between psychiatric co-morbidity and religiosity in an adult sickle cell disease population in Nigeria: a cross-sectional study

ABSTRACT Psychiatric morbidity is common among adults with sickle cell disease (SCD). Religiosity is touted as helping persons manage and cope with chronic illnesses. The role of religiosity has not been sufficiently explored in adults with SCD. This study examined the relationship between religiosity and psychiatric morbidity in an adult SCD cohort. A cross-sectional study of adults with SCD (n = 200) using a socio-demographic questionnaire, the Mini-International Neuropsychiatric Interview, the pain Visual Analogue Scale, Iron-woods Spirituality/Religiousness Index, and Oslo Social Support Scale. Sixty-five (32.5%) participants were diagnosed with psychiatric co-morbidity. Multivariate analysis showed that religiosity was independently associated with less likelihood of having a psychiatric co-morbidity after adjusting for sociodemographic, clinical factors, and the level of social support. Our findings strengthen the available evidence that spirituality/religiosity is a valuable coping strategy for those suffering from SCD and may attenuate the burden of psychiatric co-morbidity.

The Chft+ Sensor: A Novel Method to Measure Perfusion Abnormalities in Sickle Cell Disease

Introduction: Peripheral perfusion limitation is a potential biomarker of the severity and progression of sickle cell disease (SCD). Currently, there exists no direct means of quantifying perfusion deficits in SCD patients. Transcranial doppler ultrasonography offers a surrogate measure of perfusion and is highly operator dependent. Routine clinical screening of perfusion abnormalities with alternative modalities (e.g., positron emission tomography and magnetic resonance imaging) is challenging given high cost, requirement for sedation in young children, and need for trained personnel. The Combined Heat-Flux Temperature Sensor (CHFT+) is a novel noninvasive bio-heat perfusion sensor that measures peripheral perfusion in real time at depths of up to 1 cm by applying a minimal amount of heat to the skin surface. Because perfusion limitation is a hallmark of SCD, an improved understanding of its pathophysiology could potentially empower both patients and their physicians. The aim of this study was to evaluate the ability of the CHFT+ to detect differences in peripheral perfusion between healthy volunteers and patients with SCD. Materials and Methods: The present study is an ongoing, non-randomized pilot study that aims to test the CHFT+ sensor's ability to detect impaired perfusion is pediatric SCD patients. We are actively enrolling pediatric patients (age 3-17) with SCD and healthy volunteers from 2 pediatric clinics to test the sensor. Peripheral perfusion measurements were obtained at 5 locations on the body (e.g., forehead, forearms, palms). All measurements were normalized against forehead perfusion values to account for individual variations. An independent-samples t-test was conducted to compare average rates of perfusion in patients with SCD and in healthy volunteers. The goal enrollment for this study is 52 patients (26 with SCD, 26 healthy controls) to detect a two-fold difference in perfusion with a power of 0.80. Interim Results and Discussion: To date, 31 participants have been enrolled, 10 (32%) of whom were patients with SCD. Overall, average perfusion rates were lower in the SCD group when compared to the healthy group, although these differences were not statistically significant. Representative measurements of perfusion in the right and left forearms, normalized against forehead rates, are shown in Figure 1. Normalized left forearm perfusion in healthy controls vs. SCD patients: avg = 1.77, SD = 0.95 vs. avg = 1.28, SD = 0.52, respectively [t(27) = 1.80, p = 0.08]; see Fig. 1a. Normalized right forearm perfusion in healthy controls vs. SCD patients: avg = 1.80, SD = 1.01 vs. avg = 1.31, SD = 0.60, respectively [t(25) = 1.55, p = 0.13]); see Fig. 1b. Conclusions:At this time, our data suggest that the novel CHFT+ sensor is capable of detecting a modest difference in peripheral perfusion in children with SCD versus healthy controls, but this difference is not statistically significant due to limited enrollment. Additional enrollment will further define the utility of the CHFT+ sensor in this clinical population. Future studies should evaluate the sensor's capability to detect perfusion deficits in the adult SCD population, as well as measure perfusion variations that occur during SCD vaso-occlusive crises. Disclosures Diller: FluxTeq:Other: Partner.

Characterization of Sensorineural Hearing Loss in Adult Patients With Sickle Cell Disease: A Systematic Review and Meta-analysis.

To determine the prevalence of sensorineural hearing loss (SNHL) attributable to sickle cell disease (SCD) in the global adult population and to identify factors contributing to its severity. Systematic Review and Meta-analysis. We performed a comprehensive literature search for scientific articles in PubMed, Scopus, CINAHL, Web of Science, and the Cochrane Library that reported the incidence of hearing loss in populations over 18 years of age with SCD. We identified 138 studies from the initial search, 12 of which met inclusion criteria and were utilized for data analysis. A total of 636 SCD patients and 360 controls were included in the Cochrane Review Manager 5.3 meta-analysis. There was a statistically significant increase in the prevalence of SNHL in adults with SCD compared with the general population with a cumulative risk ratio (RR) of 6.03. This is the first systematic investigation of the relationship between SCD and SNHL in adult patients across the globe. SNHL is more prevalent in patients with SCD, specifically those of the HbSS genotype, than the general population likely due to the pathophysiology of the disease and its effects on labyrinthine microvasculature. The increased prevalence of SNHL in the adult SCD population warrants future research into the predictors of SNHL severity and merits routine audiometric monitoring of adult SCD patients.

Medical Resource Use and Costs of Treating Sickle Cell-related Vaso-occlusive Crisis Episodes: A Retrospective Claims Study.

BackgroundThe study investigated the economic burden of vaso-occlusive crisis (VOC) among sickle cell disease (SCD) patients, through assessment of overall utilization and costs and costs per VOC episode (regarding the number of VOC episodes and health care setting, respectively).MethodsUsing the Medicaid Analytic Extracts database, the first SCD-related diagnosis claim (index claim) between June 1, 2009–December 31, 2012 was identified among eligible adults. Patients were required to have continuous medical and pharmacy benefits for 6 months pre- and 12 months post-index. Discrete VOC claims identified within a 3-day gap were combined as a single VOC episode. Annual all-cause and SCD-related medical resources and costs were identified and stratified by number of VOC episodes during the 1-year follow-up period. Health care costs per VOC episode were also examined, stratified by care setting.ResultsEnrollees included 8521 eligible patients with a mean age of 32.88 years (SD=12.21). Of these, 66.5% had a Charlson Comorbidity index (CCI) score of 0 (no comorbidities) and 67.3% were female. The average total medical costs were US$34 136 (median=US$12 691) annually, and SCD accounted for 60% of the total costs (mean=US$20 206, median=US$1204). Patients with >3 episodes had the highest annual SCD-related costs (mean=US$58 950) across all settings. Health care resource utilization (HCRU) and costs increased substantially as the number of VOC episodes increased. This study was limited to observation of associations rather than causal inference, and by possible coding and identification discrepancies and the restricted generalizability of the population.ConclusionsVOC has a severe impact on medical resource use and costs among the adult SCD population. Further research among broader study populations is needed to facilitate the reduction of VOC episodes and thereby improve clinical and economic outcomes for SCD patients.

Demographic Features of a Mixed Urban/Rural Adult Sickle Cell Population:Opportunities and Challenges for Improving Health Care

Improvements in pediatric care since the 1970s as a result of Comprehensive Sickle Cell Centers, newborn screening, and prophylactic penicillin has led to an increase in life expectancy for patients with sickle cell disease (SCD) and has resulted in an increase in the number of adults with progressive end-organ damage/dysfunction. The inability of the U.S. Health Care system to adequately address the needs of this increasing patient population, along with stereotyping of SCD patients, has inevitably led to disparities in care, with an ever increasing disease burden and cost of care. Recognition of these issues has led U.S. Federal Health Care and Biomedical Research agencies (CDC, NIH, HRSA) to develop and implement programs to tackle this growing problem. Recently, NHLBI and NIMHD issued an RFA (HL-16-010) to address through implementation science the unmet health care needs of adolescents and adults (ages ≥15 years) with SCD. This program seeks to improve the health care and outcomes of this population through rigorous implementation of evidence-based guidelines. This initiative prompted us to analyze the demographic characteristics of the adult SCD population served by the GRU Sickle Cell Center, in an effort to better understand the opportunities and challenges posed by this initiative. The GRU Sickle Cell Center has been in existence since 1972, and serves ~1500 pediatric and adult SCD patients through its clinical program. Although based at the GRU campus in Augusta, GA (the second largest metropolitan area in the state with a population of >540,000), the Center has operated extensive outreach activities in rural south Georgia for the last 30 years, covering both pediatric and adult patients. The adult program holds monthly or every other month clinics in 5 sites in central, eastern, and southern Georgia. As of 2015, the Center has 580 active adult patients (>18 years). Fifty six percent are female and 44% male. Over half (54%) are followed at the Augusta clinic, and the remaining 46% in primarily rural outreach sites. The distribution of different genotypes is as follows: SS 392 (69%), SC 114 (20%), S-β+-thal 37 (6%), S-β0-thal 16 (3%) and others 11 (2%). The median age of the male patients is 31 (17-82), whereas for females is 34 (18-68). The median age for SS patients is 32 (17-65), and for SC is 34 (19-71). Overall, 62% of the population is in the 18-40 age group. Only 10% of the patients are >50. There is an age dependent increase in the proportion of female patients (70.6% > 61). Similarly, the proportion of SC patients increases to 56.3%, while SS decreases to 31.3% among subjects >61 years of age. Fifty-one percent of all patients (mostly SS) were prescribed hydroxyurea (HU). However, as reported earlier (Chand et al, ASH poster, 2014), only 59.9% had an adequate response; 26.3% were non-adherent, and 13.9% were on suboptimal doses. These data show that the adult SCD population in Georgia is young, with median age in the lower 30s. It also confirms the well-known observations that SC genotype and female gender are overrepresented in the older age groups. The opportunities to improve the health of this patient population in the next 5-10 years include: the existing outreach infrastructure, the partnership forged between the GRU Sickle Cell Center and some primary care practices (Family Medicine) and Hematology/Oncology practices in various outreach sites, and the implementation of an emergency department fast track pathway to treat vaso-occlusive crises in two of these outreach sites. The challenges, on the other hand, are persisting barriers to adequate/appropriate use of HU, partnering with community providers in the provision of appropriate pain management, implementation of evidence based transfusion practices in outlying hospitals and implementation of long-term evidence based health maintenance and primary care. DisclosuresNo relevant conflicts of interest to declare.

The Prevalence of Mood and Alcohol Related Disorders within the Adult Sickle Cell Disease Population and Their Impact on Healthcare Utilization

Background: Chronic pain, along with the other physical, emotional, and cognitive manifestations of Sickle Cell Disease (SCD) increases the risk of developing psychological disorders. Studies with limited sample size have suggested that depression occurs at a significantly higher proportion in SCD patients than control groups. In this study we assessed the burden of mood and alcohol dependence disorders in SCD adult patients and their effect on healthcare utilization using a nationwide sample.Methods: Inpatient and outpatient records in the Truven Health MarketScan®Database were used to calculate the prevalence of mental health disorders and hospital utilization in adult SCD patients who sought medical care during 2007 - 2012. The prevalence of mental health disorders were compared to a nationwide sample of African Americans from the Collaborative Psychiatric Epidemiology Surveys (CPES, 2001 - 2003) database.Results: Among 12,394 SCD patients with outpatient claims, the prevalence of mood disorders were 28% and 21% in females and males vs. 6% and 4% in 4,842 participants from the general African American population (all P <0.001). SCD was associated with 4 and 2.5 times higher risk of alcohol use disorders in females and males (all P <0.001). Both types of diagnoses peak at older age (50-59 years) in SCD patients vs. the younger age group (19-29) in general African Americans. Among 44,000 hospital admissions with SCD diagnosis, 47% of patients with a mood disorder were readmitted within 30 days after discharge (OR = 1.48, P <0.001). Mood disorders were associated with 0.5 days longer hospital stay (P <0.001). Neither mood nor alcohol related disorders were associated with higher cost of inpatient care.Conclusion: The high burden of mental health disorders in SCD patients justify the need to include regular screening for mental health disorders for all SCD patients and the provision of early psychological intervention to remit or mitigate symptoms and prevent higher healthcare utilization.Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number P50HL118006. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prevalence of Relative Systemic Hypertension in Ghanaian Adults with Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is associated with an increased risk of premature death in adults. Relative systemic hypertension (RSH) is associated with increased risk of vascular disorders in SCD. While drugs targeting RSH may halt the development of sickle vascular disorders, the magnitude of this problem is unknown in many countries, including in Ghana, which has ~2% incidence rate of SCD. In this study, we examined the prevalence of relative hypertension in an adult SCD patient population of the Ghana Institute of Clinical Genetics (GICG), Korle-Bu, Accra, Ghana and described their demographic characteristics, genotypes and complications.Methods: With institutional ethics committee approval, we conducted a retrospective chart review of 1000 adults aged ≥ 18 years with SCD receiving regular care at the GICG. Charts were selected as patients visited the clinic for routine care over a ten month period. SCD patients 18 years or older who had 3 blood pressure (BP) measurements on separate clinic visits for at least one year were eligible for the study. RSH was defined as systolic BP (SBP) 120 mmHg to 139 mmHg and diastolic blood pressure (DBP) 70 mmHg to 89 mmHg on at least two consecutive routine visits or visits for mild illness. We collected data on demographics, genotypes, the three most recent consecutive BPs, blood counts done on days the BPs were recorded and documented complications of SCD. A data extraction manual was used to reduce inter-observer variability. Descriptive statistics were used for data analysis. The prevalence of relative systemic hypertension in the group was calculated.Results: There were 873 eligible cases involving 319 males (36.5%) and 554 females (63.5%). Homozygous SCD (SS) and Heterozygosity for sickle cell and hemoglobin D disease accounted for 56.9% of cases, Hb SC 39% and other genotypes (e.g. S-Beta Thalassemia, Hb SF) 4%. The overall prevalence of RSH was 40.4%; Hb SS 35.8% and Hb SC 47.7%. Among the 353 patients with RSH, 145 (41.1%) were male, and 208 (58.9%) were female. The predominant genotypes in the RSH group were SS (50.4%) and SC 46.2%. Other genotypes accounted for 3.4%. Median systolic BP (SBP) for the entire cohort was 116.6 (range 86.6 - 171.1) mmHg, and the median diastolic BP (DBP) was 70.3 (range 48 to 113.6) mmHg. Median blood pressures were higher in patients with Hb SC (males: 123/75, females: 122/76 mmHg) than those with Hb SS (males: 117.6/67, females 111/67mmHg). Complications were noted as follows; avascular necrosis (6.9%), other bone disease (1.1%) leg ulcers (6.3%), cholelithiasis (3.7%), cardiopulmonary 1%, and renal 1%. Pearson correlation coefficient showed associations between blood pressure, age, hemoglobin (Hb), and WBC. There was a positive correlation between SBP and age (r = 0.088, p = 0.009) and total Hb (r = 0.106, p = 0.002). Spearson's correlation revealed significant positive correlation between SBP and leg ulcers (r = 0.074, p ≤ 0.05); DBP and leg ulcers (r = 0.119, p ≤0.01); DBP and priapism (r = 0.075, p =0.026) and DBP and cholelithiasis (r = 0 .086, p=0.011).Conclusions: There is a 40.4% prevalence of RSH, which to the best of our knowledge represents the first estimate of this condition in the Ghanaian adult SCD population. The prevalence among Hb SS patients is 35.8% compared to the 44% previously reported in the US. There is significant positive correlation of BP with Hb, leg ulcers, priapism and cholelithiasis. Future prospective studies using standardized BP monitoring are warranted to validate preemptive treatment of RSH in SCD. DisclosuresNo relevant conflicts of interest to declare.

Overactive bladder in adults with sickle cell disease.

To characterize the prevalence and impact of nocturnal enuresis and overactive bladder (OAB) symptomatology in the adult sickle-cell disease (SCD) population. We performed a single-center, cross-sectional study of adult SCD patients from October 2012 to February 2014, using the validated Pfizer OAB short form questionnaire and brief voiding history surveys. Patient responses and scores were compared to that of controls having normal or sickle cell trait hemoglobin genotypes. A group of 239 SCD patients (116 males, 123 females) were compared with 104 normal and 57 sickle cell trait patients. Seven of 239 (2.9%) SCD patients compared to none of the 161 patients without SCD (P = 0.04) reported current nocturnal enuresis. The median age of nocturnal enuresis cessation was higher in SCD patients (12.0, IQR 9.0-15.0 years) compared to that of both normal (7.5, IQR 6.0-9.8 years) and sickle cell trait (7.5, IQR 6.0-8.8 years) groups (P < 0.0001). Ninety-three of 239 (38.9%) SCD patients compared to 17 of 104 (16.3%) normal and 11 of 57 (19.3%) sickle cell trait had scores indicating OAB symptomatology (P < 0.0001). Patients with SCD had higher OAB symptom severity and lower health-related quality of life (HRQL) scores compared to the normal and sickle cell trait groups (P < 0.0001 and P < 0.0001, respectively). We demonstrate an elevated rate of nocturnal enuresis and OAB symptoms in the adult SCD population. An OAB phenotype may be an under-recognized complication of SCD irrespective of age. Neurourol. Urodynam. 35:642-646, 2016. © 2015 Wiley Periodicals, Inc.

Pain Control in Sickle Cell Disease Patients: Use of Complementary and Alternative Medicine

To examine the factors associated with the use of complementary and alternative medicine (CAM) as reported by patients attending an adult sickle cell clinic at a tertiary institution. Cross-sectional survey. This study was conducted in a university tertiary care adult sickle cell clinic. Adult sickle cell patients. Following Institutional Review Board approval, a questionnaire was administered to patients in a sickle cell clinic to examine their use of CAM for managing pain at home and while admitted to the hospital. Of the 227 respondents who completed the questionnaire, 92% experienced pain lasting from 6 months to more than 2 years. Two hundred and eight (91.6%) indicated that they have used CAM within the last 6 months to control pain. The frequency of CAMs use was higher among females, singles, those with more education, and higher household income. This study shows that a substantial majority of sickle cell patients live with pain on a regular basis and that there is substantial CAM use in the adult Sickle cell disease population. Being female and having a high school or higher education were significantly correlated with the use of CAM in sickle cell patients. A variety of CAM therapies are used, with the most common being prayer.

Epidemiology, Management and Outcome Of Priapism In Children and Adolescents With Sickle Cell Disease: A Pediatric Health Information System Database Analysis

BackgroundPriapism is a known but largely understudied complication of sickle cell disease (SCD). The epidemiology of priapism in children and adolescents with SCD is not well characterized especially the pattern of hospitalization. Data are scarce about the role of blood transfusion and surgical therapies in the management of priapism in SCD. Recent expert opinion questions the efficacy of blood transfusion and recommends early urological interventions in these patients (Merritt et al. Can J Emerg Med 2006, Kato GJ. J Sex Med. 2012). As hospitalization consumes lots of economic resources, we studied the trend and outcome of hospitalization for priapism in children with SCD over the last decade. MethodsWe used the Pediatric Health Information System (PHIS), an electronic database of children's hospitals in the US. Patients ≤ 21 years of age with SCD from 33 hospitals from 2000-2011 were analyzed. SCD, priapism and all related conditions were identified by ICD-9 codes. We examined patient demographics, timing of hospitalizations, treatment details, RBC transfusion (simple and exchange transfusion), and urologic procedures (including aspiration and irrigation of corpus cavernosum, corpora cavernosa-corpus spongiosum shunt and corpora-saphenous shunt) and hospital charges. With the inherent skewness of the length of stay and cost data, we used non-parametric analysis when comparing summary statistics. Given the level of over-dispersion, a negative binomial model was used to determine adjusted length of stay and cost. A p-value <.05 was considered statistically significant. ResultsFrom 2000 to 2011, there were 7929 unique male pediatric patients with SCD identified. Among these 465 (5.9%) patients had a diagnosis of priapism and accounted for 1069 priapism related hospitalizations. Overall, the number of new sickle cell patients with priapism getting hospitalized remained stable (Figure 1A). The demographic and baseline characteristics of these patients are shown in Figure 1B. In 63% (673/1069) of the priapism related hospitalizations, patients received conservative treatment whereas blood transfusion, urologic procedures or both were performed in 25.2% (269/1069), 6.6% (71/1069) and 5.2% (56/1069) of the hospitalizations respectively. Five percent (51/1069) of priapism related hospitalizations required ICU care, 1% (15/1069) required mechanical ventilation and there was no in-hospital mortality. Average length of stay for priapism related hospitalization was 3.8 days. Multivariate regression analysis showed that the presence of VOC, ACS, blood transfusion, and urologic procedures were independently associated with increased length of stay and costs (Table 1). Multivariate analysis showed neither transfusion nor urologic procedures were associated with neurological complications observed during priapism related hospitalizations. [Display omitted] Table 1Predictors of length of stay and hospital costs in priapism related hospitalizationsVariableLength of Stay (LOS)Total Hospital CostCoefficientStd. Errorp-valueAdjusted LOS (days)CoefficientStd. Errorp-valueAdjusted Cost (in $1000 dollars)ACS0.4030.101<.00015.840.6640.130<.000117.25VOC0.3790.060<.00015.770.2530.1010.01214.04No Transfusion/Procedurereference----3.57reference----8.04Transfusion-only0.3340.069<.00014.990.4740.107<.000112.91Procedure-only0.2570.0980.0094.610.3570.1110.001311.49Both Transfusion/Procedure0.5730.106<.00016.330.8950.141<.000119.67 ConclusionsIn our largest pediatric in-patient sickle cell cohort, the prevalence of priapism was 5.9%. New inpatient diagnoses of priapism among children with SCD remained constant overtime as previously reported in adult SCD population (Chrouser et al. Am J Surg 2011). Majority of our patients received conservative treatment and urologic procedures were utilized infrequently, again consistent with adult literature. Both blood transfusion and urologic procedures were associated with increased length of stay and costs but not with neurological complications. There is a strong need for prospective, multi-institutional trials to define the role of blood transfusions, surgical procedures and other novel therapies to improve the outcome. Disclosures:No relevant conflicts of interest to declare.

Exploratory Study of Haptoglobin Levels by Genotype in Adult Sickle Cell Patients

Abstract 2145Patients with sickle cell disease (SCD) have both extravascular and intravascular hemolysis; it is estimated that 1/3 of the hemolytic process in SCD is intravascular. Hemoglobin (Hb) released from hemolyzed red blood cells is bound by haptoglobin (Hp) in a 1:1 stochiometric complex, which is then taken up by macrophages through the scavenger receptor, CD163. When the binding capacity of haptoglobin is exceeded, concentration of cell free Hb in plasma increases, excess cell free Hb is a nitric oxide (NO) scavenger and leads to a NO depletion state. This, in turn, leads to endothelial dysfunction with increased expression of adhesion molecules and inflammatory markers, platelet activation, and an inflammatory state. This process has been incriminated in the pathogenesis of certain complications of SCD and other chronic hemolytic states with a significant intravascular hemolytic component. These include increased pulmonary artery pressure (PASP), priapism, leg ulcers, and renal dysfunction. In addition to these deleterious effects of excess cell free Hb, the fate of Hb—Hp complexes may play a significant role in the pathogenesis of the inflammatory state. Hp is a polymorphic protein with two well characterized alleles, Hp-1 and Hp-2. A large body of evidence suggests that Hp-2 allele si a major susceptibility gene for the development of vascular complications (coronary artery restenosisand cardiovascular disease). This has been attributed to the generation of a more potent inflammatory response after the binding of the larger Hp-2/Hb complexes to the CD163 receptor. We previously reported on the distribution of Hp genotypes in our pediatric and adult populations [Hughes et al, Blood 106(11), 3805 30(b), December 2005] and more recently have shown that binding of Hp-2-Hb complexes to mononuclear cell cultures from SCD patients resulted in a 3–12 fold higher inflammatory cytokine release (GM-CSF, IL1, IL-10, and TNF) compared to that observed with Hb-Hp1 complexes [Bora et al, Blood 112(11):513(1441), 2008]. We studied the haptoglobin levels in the plasma of SCD patients on and off hydroxyurea (HU) and in relation to their Hp genotype. Since clinical assays for haptoglobin are rather insensitive below 6 mg/dl, we used a sensitive ELISA (Genway Biotech) technique to quantify Hp. Hp genotypes are determined by a previously published PCR procedure, which resulted in a 3245 bp product for Hp-1 and 4945 bp for Hp-2 (Fig. 1).The distribution of Hp genotypes showed a paucity of the Hp-2-2 (17%) in this adult SCD population with 31% Hp-1-1 and 52% Hp-1-2 genotypes, confirming our previous observations. Hp concentration was strikingly lower in the SCD population (N-48) compared to normal controls (N=3); 2.31 mg/dL vs.45.58 mg/dL, p=0.01. There was no significant difference in Hp concentration among SCD patients with different Hp genotypes (Fig. 2). Similarly Hp levels between patients on and off HU did not differ significantly. Our findings are confirmatory of the data reported recently by Moller et al (Brit. J. Haematol, 153, 105–11, 2011) in 41 children with SCD, who did not find a significant difference in Hp levels in patients on and off HU. To our knowledge this is the first study of Hp levels in adult patients with SCD and different Hp genotypes. A larger study in this patient population looking at Hp levels in relation to both Hp genotype and HU usage is underway. We anticipate that this will provide insights into the role of Hp and its polymorphisms and its contribution to the phenotypic heterogeneity of SCD. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Retrospective Review of the Natural History of Pulmonary Hypertension in Sickle Cell Disease Demonstrates That Progressive Enlargement of the Left Atrium Is a Strong Predictor of Death.

Abstract 1529Poster Board I-552Pulmonary hypertension (PAH) is an independent risk factor for death in sickle cell disease (SCD). We performed a retrospective chart review to determine the natural history of PAH in our adult SCD population. We hypothesized that increased pulmonary artery pressures seen during hospitalizations for painful crisis or acute chest syndrome would be reflected in a faster progression of PAH measured during steady state. We reviewed charts and echocardiograms of 362 patients seen at Duke University from January 1980 to March 2009. A total of 878 2D echocardiograms were reviewed, with 196 patients having 2 or more echocardiographic procedures. Fifth-three of the 81 patients who died during this period had had at least 2 or more echocardiograms. Studies were considered done at steady state if they were performed as an outpatient procedure. Out of 878 total echocardiograms, 460 had either no measurable tricuspid regurgitation jet (TR) or failed to report it and were excluded from further analysis, leaving 418 echocardiograms in 252 patients (167 at steady state and 251 as inpatient). Among patients with multiple echocardiograms and measurable TR jet performed at steady state, we used a linear mixed model to identify a mean yearly rate of progression of 0.04 m/s (p<0.001, 95% CI 0.02 to 0.05). Patients in whom echocardiograms were performed as inpatients had higher pressures (mean difference 0.24 m/s, p<0.01), as reported previously by other authors, but they had a similar rate of progression at steady state as did the patients without inpatient echocardiograms (Figure 1). Contrary to our hypothesis, therefore, higher inpatient TR jet velocities did not affect the rate of progression of PAH at steady state. Furthermore, the rate of progression of TR jet velocity at steady state was also not statistically significantly related to mortality (p=0.57). Interestingly, however, patients who died had an inpatient TR jet velocity slope of 0.08 m/s/year, compared to patients who were alive at the end of the study period (0.03 m/s/year, p=0.04). Furthermore, in patients with PAH, an increase in the left atrial diameter of 1 cm increased the risk of death by 50% (OR 1.47, p=0.001). Despite the potential selection bias inherent to a retrospective review, our study was able to estimate a mean progression of PAH of 0.04 m/s year in SCD patients at steady state and to identify increasing left atrium enlargement as a strong predictor of death. In this cohort, findings of a faster progression of PAH, measured by inpatient echocardiograms, did not correlate with changes in the rate of progression of PAH at steady state, although it was associated with an increased risk of death. Improved knowledge of variables characterizing the natural history of PAH in SCD patients should support further development of therapeutic approaches targeting PAH. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Demographic and Socio-Economic Features of a Cohort of Adult Sickle Cell Disease Patients.

Abstract 4616 IntroductionDespite improvements in diagnosis, preventive care and treatment, care of sickle cell disease (SCD) patients remains difficult. The majority are from lower socio-economic strata, poorly educated and from single parent households. The racial divide between patients (who tend to be almost all black) and their health care providers (who tend to be predominantly non black) can adversely affect the quality of care when stereotypes are assumed. We examined the demographic and socio-economic features of patients in our adult sickle cell disease program. Patients and MethodsWe retrospectively reviewed data on 118 patients that entered our program between February 2005 and October 2008. Our catchment area included parts of rural Mississippi, Tennessee and Arkansas as well as a major urban community. We reviewed the following demographic characteristics: age, gender, patient's marital status, parent's marital status, employment status, highest level of education, health insurance status and referral source. We then contrasted the characteristics of those with SC (which tends to be milder) with SS/Sβ0 sickle cell disease (which is phenotypically more severe). Continuous variables were evaluated using t-test. Chi-square test was used to assess categorical variables. ResultsThe results are depicted in the table.Demographic VariablesOverall N = 118SC n=27*SS/Sβ0 n=74*p-valueAge (mean ± s.d.)26.5 ± 11.932.8 ± 14.924.4 ± 9.40.0104Age groups (%)0.0343 à< 2062 (53)335520 to < 3022 (19)192030 to < 4018 (15)191640 and greater16 (13)308Gender (%)NSMale58 (49)6351Female60 (51)3749Patient's Marital status (%)NSàDivorced5 (4)71Married20 (16)3015Never married89 (77)5982Unknown3 (3)41Parents' marital status (%)NSàDivorced20 (17)718Married43 (37)4437Never married39 (33)3034Separated2 (2)03Unknown13 (11)198Employment (%)0.0073Currently employed26 (23)4215Currently unemployed25 (22)2718Never employed19 (16)424Student44 (39)2742Education (%)NSàCollege35 (32)3630GED/ finished HS60 (55)5652Grades K-81 (1)01HS dropout/ grades 9,10,1112 (10)415Other/vocational2 (2)41Health insurance (%)0.048Medicaid59 (51)4457Medicare11 (9)119None6 (5)151Third party41 (35)3032Referral source (%)NSàPCP/Other38 (32)4136Self22 (19)2219SJCRH58 (49)3750Abbreviations: SHPFH, sickle hereditary persistence of fetal hemoglobin; GED, General Educational Development; HS, High School; SJCRH, St. Jude Children's Research Hospital, PCP primary care providerStatistically significant at significant level 0.05àCells had inadequate number of counts. Chi-square may not be a valid test.*Excludes 17 patients with Sβ+/SHPFH/other, not included in the comparison because of the small numbers. ConclusionsWe describe the demographic and socio-economic features of a cohort of 118 patients seen in an academic center with a diverse catchment area. In spite of adverse family circumstances, relatively high proportion of the cohort was college educated (32%) or graduated from high school/GED (55%). 61% of the patients are either currently employed or current students. These results are quite contrasting to the general perception about the adult sickle cell disease population. Disclosures:No relevant conflicts of interest to declare.

Pulmonary hypertension in an adult sickle cell population in Guadeloupe

Pulmonary hypertension (PH) is a severe complication of sickle cell disease (SCD). The main purpose of this study was to evaluate the prevalence of PH in an adult SCD population in Guadeloupe. Echocardiography findings of 427 patients with SCD were analyzed. Subjects with a pulmonary artery systolic pressure (PASP) > 30 mm Hg, at rest, were studied. PH was found in 49 (11.5%) SCD patients. Mean age was 37 years and mean PASP was 40 mm Hg. The most frequent symptom was exertional dyspnea. Thirteen subjects (26%) had left heart diseases. In the overall study population, 22 (5%) patients died. Seven (14%) patients had PH and 15 (4%) were PH free, p = 0.006. An early PH screening is recommended in SCD patients at steady state owing to the absence of specific symptoms and to the significant mortality rate related to this complication.