The most common symptom for persons with sickle cell disease (SCD) is severe pain from vaso-occlusive crisis (VOC), which often requires treatment in the emergency department (ED). Many patients with SCD experience numerous unmet psychological and social complications (e.g., depression, anxiety, transportation challenges) which can contribute to increased pain. These needs have not been explored among a sample of ED patients experiencing a VOC in an ED. The objective of this quality improvement (QI) project was to implement a social worker screening of all adults with SCD during an ED visit and explore psychological and social needs. The QI team developed a 15-item screening tool to be administered by the ED social worker. The tool assesses for self-reported anxiety and depression, transportation barriers, prescriptions barriers, assessment of missed days of work, and other unmet needs. Upon arrival to the ED, an automatic page to the ED social worker is sent. Over a 12-month period 134 screens were conducted. Depression and anxiety were reported during 31% and 22% of all screenings respectively. During all screenings patients reported the following barriers (frequencies): transportation to clinic appointments (38%), having to wait for a ride to the ED (29%), obtaining prescriptions (33%) and being unable to afford co-pay or prescriptions (26%). Additional barriers to care included limited Medicaid options, and communication concerns with ED staff. Implementation of a social worker screen in the ED is feasible, and there was overwhelming support of the process by patients and social workers. An opportunity exists for ED social workers or case managers to identify and refer patients to healthcare services designed to meet the unmet needs of persons with SCD who experience a VOC and an ED visit. We believe these needs may contribute to increased pain and ED use; research is necessary to explore this hypothesis. Abstract source

Central nervous system sensitization (CS) is common to a number of chronic pain conditions. Adult patients with sickle cell disease (SCD) often have chronic pain. Both animal and human evidence suggests that central sensitization is a factor in its development or maintenance. Patients with SCD are often treated with opioids, which can produce paradoxical pain facilitation through central mechanisms. This analysis examined the relationship of chronic opioid therapy (COT, those prescribed daily long-acting opioids) to central sensitization with SCD. Using baseline quantitative sensory testing, we identified a subgroup of participants with SCD showing a pattern of CS (n=21) and a group showing no or low CS (n=17) using norms derived from healthy controls. High CS participants reported greater baseline pain (Brief Pain Inventory Severity mean = 3.55 vs. 0.54, p<<0.001). Demographics (sex, age, and education) and measures of SCD severity were entered into a multivariable model predicting central sensitization along with COT. After backward stepwise model simplification, baseline pain dropped out of the model and chronic opioid therapy was the strongest individual baseline predictor of CS (OR=1.53, 95% CI = 1.14, 2.05). In prospective daily diary measures following baseline assessment, average daily pain and pain catastrophizing were associated with CS. Entering chronic opioid therapy into these models reduced the predictive power of average daily pain below statistical significance, though daily catastrophizing remained an independent predictor of CS. The CS group had a higher proportion of participants on chronic opioid therapy (61.9%) relative to the no/low CS group (13.3%) and this association was stronger than, and statistically independent from, baseline pain. The results raise the possibility that opioid-induced hyperalgesia may contribute to chronic pain via central sensitization in SCD. Prospective studies of central sensitization and pain outcomes from chronic opioid therapy in SCD are warranted. Supported by grant NIH/NHLBI 5R01HL098110. Abstract source

Sickle cell disease is caused by a mutant form of hemoglobin that polymerizes under hypoxic conditions, increasing rigidity, fragility, calcium influx-mediated dehydration, and adhesivity of red blood cells. Increased red cell fragility results in hemolysis, which reduces nitric oxide (NO) bioavailability, and induces platelet activation and inflammation leading to adhesion of circulating blood cells. Nitric Oxide inhibits adhesion and platelet activation. Nitrite has emerged as an attractive therapeutic agent that targets delivery of NO activity to areas of hypoxia through bioactivation by deoxygenated red blood cell hemoglobin. In this study, we demonstrate anti-platelet activity of nitrite at doses achievable through dietary interventions with comparison to similar doses with other NO donating agents. Unlike other NO donating agents, nitrite activity is shown to be potentiated in the presence of red blood cells in hypoxic conditions. We also show that nitrite reduces calcium associated loss of phospholipid asymmetry that is associated with increased red cell adhesion, and that red cell deformability is also improved. We show that nitrite inhibits red cell adhesion in a microfluidic flow-channel assay after endothelial cell activation. In further investigations, we show that leukocyte and platelet adhesion is blunted in nitrite-fed wild type mice compared to control after either lipopolysaccharide- or hemolysis-induced inflammation. Moreover, we demonstrate that nitrite treatment results in a reduction in adhesion of circulating blood cells and reduced red blood cell hemolysis in humanized transgenic sickle cell mice subjected to local hypoxia. These data suggest that nitrite is an effective anti-platelet and anti-adhesion agent that is activated by red blood cells, with enhanced potency under physiological hypoxia and in venous blood that may be useful therapeutically. Abstract source Full text Full text (PMC)

Sickle cell disease (SCD) is one of the common inherited blood disorders in humans and has been associated with decreased dietary intake which results in poor nutritional status and impaired growth. Nutrition is one of the most important but often forgotten aspect of care of patients with chronic disorders and there have been emerging concern in literature on increased nutritional needs of SCD patients. This paper sought to review the available literature on the roles of individual nutrients in the pathophysiology and management of SCD among children. Children with SCD have been shown to exhibit suboptimal status with respect to both macronutrients and micronutrients. Thus, nutrition could play an important role in the management of SCD. However, there is paucity of evidence coming from trials with large sample sizes to support the suggestion that supplementation with various nutrients that have been considered in this review will be helpful. Abstract source Full text

Background: The Build, Educate, Advance, Transition, in Sickle cell disease (BEATS) music therapy program was developed to address health challenges faced by adolescents/young adults (AYA) with sickle cell disease (SCD) during the transition to adult medical care. Objective: The purpose of this study was to investigate the effects of BEATS on self-efficacy, trust, knowledge about SCD, and adherence in adolescents/young adults (AYA) with SCD. Subjects: Thirty AYA with SCD, 18-23 years old, recruited from an adult SCD clinic agreed to participate in four BEATS sessions over 1 year. Methods: Self-efficacy, trust and SCD knowledge were measured prospectively at baseline and months 3, 6, 9, and 12. Adherence to clinic appointments and healthcare utilization were measured retrospectively from medical records. A repeated measures linear mixed-effect model with compound symmetry covariance structure was used to fit the data. Results: BEATS participants demonstrated a significant improvement in SCD knowledge (p = 0.0002) compared to baseline, an increase in acute care clinic, but not emergency department, utilization (p = 0.0056), and a non-significant improvement in clinic attendance (p = 0.1933). Participants' subjective evaluations revealed a positive response to BEATS. There were no significant changes in self-efficacy, trust, hospital admissions, or blood transfusion adherence. Conclusion: Culturally tailored, developmentally appropriate music therapy transition interventions can concretely improve SCD knowledge and may improve transition for AYA with SCD. Abstract source Full text

Background: A subset of adults with sickle cell disease (scd) heavily utilizes the emergency department (ed) and hospital. The objective of our study was to determine the efficacy of a multidisciplinary strategy to address unmet needs in highly utilizing adults with scd. Methods: In a prospective study, adults with scd with ≥10 admissions per year were assessed by a multidisciplinary team for gaps in medical, social, and psychological care. Thereafter, the team decided upon the subject's predominant domain that drove admissions and instituted an interventional plan. All plans included an opioid management strategy. Preintervention and postintervention admission rate, as well as opioid use, was compared. Results: Twelve subjects were enrolled. Median rate of ed and hospital admissions preintervention was 25 per year. The predominant domains identified were social needs (n = 6), psychological disorder (n = 1), and substance use disorder (n = 5). Multifaceted interventional plans were developed to address a wide range of gaps in care, but an opioid management strategy was the only intervention successfully completed. Even so, when the preintervention versus postintervention admission rate was compared, regardless of the domain, there was a 40 percent decline in hospital admissions (p = 0.03). Consistent with the successful implementation of an opioid management plan, the decrease in admissions was accompanied by a 37 percent decrease in intravenous opioid use (p = 0.02) and 10 percent decrease in oral opioid use (p = 0.04). Conclusion: An opioid management strategy, as part of a larger effort to improve care for high-utilizing adults with scd, decreased rate of admissions and opioid use. Abstract source

Sickle cell disease (SCD) represents one of the most common monogenic blood disorders worldwide, with an incidence of over 300,000 newborns affected per year. Reproductive challenges for men and women with SCD have been previously reviewed; however, evidence-based strategies to prevent and manage infertility and increase fecundity are lacking in women with SCD, which is one of the most important factors for quality of life. Areas covered: This review article summarizes the known risk factors for infertility, low fecundity, and premature menopause related to SCD. Expert commentary: Women with SCD have unique risk factors that may impact their ability to conceive, including chronic inflammation, oxidative stress, transfusion-related hemochromatosis, and ovarian sickling, causing ischemia and reperfusion injury to the ovary. Contraception is strongly recommended while on hydroxyurea therapy during reproductive years and discontinuing hydroxyurea for family planning and during pregnancy based on teratogenicity in animal studies. Hematopoietic stem cell transplantation (HSCT), the only curative therapy, sometimes involves conditioning regimens containing alkylating agents and total body irradiation that contribute to infertility and premature ovarian failure. Prior to HSCT or gene therapy, we strongly recommend referral to a reproductive endocrinologist to discuss fertility preservation and surrogacy options for all women with SCD. Abstract source Full text

Purpose of review: To review recent literature pertaining to sickle cell retinopathy (scr) and, in particular, sickle cell maculopathy. Recent findings: Several recent studies suggest that macular perfusion abnormalities seen in patients with sickle cell disease of various genotypes may affect both the superficial and deep capillary plexi, with a predilection for the deep capillary plexus. Further, these changes may be associated with areas of macular thinning, as well as with peripheral retinal ischemia, even in individuals without visual symptoms, contrary to what has previously been described in both diabetic retinopathy and retinal vein occlusion. Several cases also suggest that paracentral acute middle maculopathy may be the pathophysiologic mechanism by which microvascular occlusion leads to macular thinning. Summary: Sickle cell disease can manifest in a number of ways within the orbit as well as intraocularly because of its nonspecific vasoocclusive episodes. However, scr is the most common ophthalmic manifestation of this disease. Historically, scr has been considered a peripheral retinopathy, but the development and use of spectral-domain optical coherence tomography and optical coherence tomography angiography suggest that significant macular vascular changes occur early in this disease, even in asymptomatic individuals. Abstract source Full text

Background/Objective: Sickle cell disease (SCD) and hydroxyurea have implications for fertility and reproductive health. The goal of this study was to examine desire for parenthood and reproductive health knowledge among a cohort of adolescent and young adult (AYA) with SCD receiving hydroxyurea and their caregivers at a large pediatric academic center. Methods: Patients with SCD were approached from September 2016 to July 2017 if they were: (1) 12-20 years old, (2) prescribed hydroxyurea for at least 6 months, (3) proficient in English, and (4) accompanied by a caregiver who was proficient in English and willing to participate. Participants self-reported sociodemographic characteristics and completed surveys to assess their/their child's desire for parenthood and other life goals, and reproductive health knowledge. Results: Eighteen patient-caregiver dyads completed the study (78.3% of those eligible); 61.1% indicated that they wanted to have future biological children. Few participants reported receiving information about fertility (16.7% of AYA and 27.8% of caregivers) or birth control (11.1% of AYA and 22.2% of caregivers) from their/their child's health care provider, and the majority had received no information on these topics. Less than half of participants reported that SCD (22.2% of AYA and 50.0% of caregivers) or hydroxyurea (11.1% of AYA and 27.8% of parents) could potentially impair fertility. Conclusions: Biological parenthood was important to this cohort yet fertility and reproductive health knowledge was low, suggesting that clinicians should prioritize conversations about infertility risk and birth control options with AYA with SCD on hydroxyurea and their caregivers. More research is needed to identify optimal approaches to these discussions. Abstract source Full text

BACKGROUND: Informed by the Pediatric Self-Management Model, the present study tested relationships between parent and family functioning, sickle cell disease (SCD) self-management, and health outcomes for children with SCD. METHOD: 83 children with SCD and a parent completed baseline data as part of a larger investigation of a family-based, problem-solving intervention for children with SCD (M age = 8.47). Youth and parents completed a measure of child health-related quality of life (HRQOL), and parents completed measures of family efficacy, parenting stress, and SCD self-management. SCD pain episodes and urgent health utilization information over the past year were obtained via medical chart review. RESULTS: SCD self-management mediated the relationship between parent-reported family efficacy and parent proxy HRQOL, as well as the relationship between parenting stress and child and parent proxy HRQOL. Mediation models were nonsignificant for outcomes beyond HRQOL, including SCD pain episodes and urgent health utilization. CONCLUSION: Fostering family efficacy and reducing parenting stress may be meaningful intervention targets for improving SCD self-management and child HRQOL among school-aged children. Although findings were consistent with the Pediatric Self-Management Model in terms of HRQOL, the model was not supported for pain episodes or urgent health utilization, highlighting the need for multi-method, longitudinal research on the SCD self-management behaviors that are linked to preventable health outcomes. Abstract source Full text