Background: In the 52-week SUSTAIN study, crizanlizumab 5.0 mg/kg significantly reduced the frequency of SCPCs versus placebo (1.6 vs 3.0, P=0.01) and increased the time to first on-treatment SCPC (4.1 vs 1.4 months, P=0.001) in patients with sickle cell disease (SCD).   Objectives: To evaluate time to first SCPC in SUSTAIN study subgroups and the likelihood of not experiencing SCPC for the duration of the trial using post hoc analyses.   Design/Method: SUSTAIN was a randomized, double-blind, placebo-controlled, phase 2 study (NCT01895361). Inclusion criteria were: SCD patients aged 16-65 years; 2-10 SCPCs in previous 12 months; concomitant hydroxyurea use permitted if ≥6 months and stable dose for ≥3 months. Patients were randomized 1:1:1 to receive intravenous crizanlizumab 5.0 mg/kg, 2.5 mg/kg, or placebo. Study treatments were administered on days 1 and 15, then every 4 weeks to week 50, with the final assessment at week 52. Median time to first SCPC after first dose was summarized for crizanlizumab 5.0 mg/kg or placebo in these subgroups: 2-4 or 5-10 SCPCs in previous 12 months; SCD genotype; and hydroxyurea use at baseline. Hazard ratios (HRs) for crizanlizumab 5.0 mg/kg versus placebo were calculated based on Cox regression analysis, with treatment as a covariate. Descriptive statistics were used to summarize the frequency of patients who were SCPC event-free for the duration of the study by prior SCPC events, SCD genotype, and hydroxyurea use at baseline.   Results: 67 patients received crizanlizumab 5.0 mg/kg and 65 received placebo. There was a meaningful delay in time to first SCPC with crizanlizumab 5.0 mg/kg versus placebo observed in the entire study population. The effect was present in both SCPC subgroups, and the largest treatment difference was observed in HbSS SCD versus other genotypes (4.1 vs 1.1 months; HR: 0.50). In patients taking hydroxyurea who experienced 2-10 SCPCs in the previous year, time to first on-study SCPC was longer with crizanlizumab 5.0 mg/kg versus placebo (2.4 vs 1.2 months; HR: 0.58). A greater proportion of patients treated with crizanlizumab 5.0 mg/kg were SCPC event-free versus placebo in each of the analyzed subgroups. One third of patients who were taking hydroxyurea and treated with crizanlizumab 5.0 mg/kg were SCPC event-free during the study versus 17.5% with placebo, possibly suggesting an additive effect.   Conclusion: With crizanlizumab 5.0 mg/kg, there was a clinically meaningful delay in time to first SCPC and an increased likelihood of being SCPC-free versus placebo in all subgroups investigated.   Abstract source

Priapism is a pathological condition of persistent penile erection in the absence of sexual arousal or desire. It is a urological emergency and its identification is important as lack of prompt treatment can result in erectile dysfunction.The aim of this study was to estimate and describe the characteristics (number of episodes, duration, time of occurrence and evolution) of priapism in patients with sickle cell disease. A bibliographical research was carried out in PubMed, searching for papers published in the last 5 years. Thirteen scientific articles were included in this review.The main results were: 1) the highest prevalence of priapism in males reported was 48.0% and the lowest 0.67%; 2) six studies were carried out on the African Continent (46.1%), three in America (23.1%), two in Europe (15.4%) and two in Asia (15.4%); 3) the main goal of ∼50.0% of the studies was to determine the rate of priapism in patients with sickle cell disease; 4) there was predominance of sickle cell anemia patients [homozygous Hb S (HBB: c.20A>T) genotype]; 5) the minimum age of patients with priapism was 7 years old and the maximum 30 years.In general, the episodes of priapism occurred during sleep, were recurrent and had variable duration. The prevalence of priapism is not real and the explanations include underreporting by patients, lack of awareness by physicians and lack of proper prospective studies. Priapism is a complication that deserves close attention due to its significant impact on the life of the patient with sickle cell disease and, therefore, should be further clarified.  Abstract source

Sickle cell disease (SCD) is a generic term for an inherited group of disorders that includes homozygous sickle cell anaemia (SS), sickle cell/haemoglobin C (SC) sickle cell/β-thalassemia (S/β thal) and other compound heterozygous conditions. SCD is characterised by the presence of the mutated β‐globin gene, HBBs (also termed βs‐globin). On de‐oxygenation, this forms a polymeric structure resulting in deformed, rigid red blood cells, and is associated with a chronic haemolytic anaemia due to shortened red cell life span and vaso‐occlusion causing frequent episodes of severe bony pain (vaso‐occlusive crises) and other acute and chronic complications. These include an increased risk of stroke, pulmonary hypertension, acute and chronic lung damage, chronic renal failure and leg ulcers. Fetal haemoglobin (haemoglobin F, HbF, α2ϒ2) is protective against these complications and infants are relatively protected in the first few months of life before HbF in infancy is replaced by HbS (α2βS2) rather than adult haemoglobin (HbA, α2β2). Co‐inheritance of raised HbF levels is also associated with a milder phenotype.   Abstract source Full text

Pain is the most common symptom in sickle cell disease (SCD) and individuals with SCD exhibit pain hypersensitivity. Hypnosis can have beneficial effects on pain modulation, but it is unknown whether pain-related anxiety—a cognitive-affective factor also associated with pain modulation—attenuates the effects of hypnosis in individuals with SCD.  This study examined if pain-related anxiety alters the effects of hypnosis on laboratory pain responsivity in adults with and without SCD. The sample included 14 adults with SCD and 14 race-matched healthy controls. Participants completed the Pain Anxiety Symptoms Scale (PASS-20) at baseline. Pain tolerance (°C), threshold (°C), and intensity (0–100) were collected during a standardized thermal pain protocol before and during a hypnosis session.Change in pain outcomes indicated participants’ responses to hypnosis. Nonparametric tests were used and a median split determined within group levels of pain-related anxiety. Pain-related anxiety did not significantly differ across SCD and non-SCD groups, and was not associated with pre-hypnosis pain tolerance or threshold in either group. In adults with SCD who had lower levels of pain-related anxiety, pain tolerance increased 5.68°C during hypnosis compared to 1.97°C in those with high anxiety (Z = -1.98, p < .05). The effect on pain threshold approached significance (1.97°C vs. -.38°C, Z = -1.85, p = .06). There was no effect of pain-related anxiety on change in pain responsivity in healthy controls.Results partially align with other pain anxiety research and suggest that higher pain-related anxiety may be particularly important to consider in individuals with SCD as it may attenuate pain modulatory effects of hypnosis. Further, in individuals with higher pain-related anxiety, a single hypnosis session may be insufficient to reduce modulatory effects of anxiety on pain responsivity. Thus, examination of long-term treatment effects in a larger sample is needed to confirm underlying mechanisms affecting hypnosis treatment responses in individuals SCD.  Abstract source

“You’re too pretty to have a disease,” declared the nurse in the emergency department (ED) dismissing Constance Benson’s reports of unbearable pain, a byproduct of her sickle cell disease (SCD). Constance, who is in her late twenties, is a professional actress and model living in Kennesaw, GA. It wasn’t until Constance’s blood tests came back with information about her blood count that she was treated with the care and attention she deserved. “If I had a broken leg, it would be different. If I was having a heart attack, it would be different. But because I had sickle cell disease and I look like a normal person, my pain was dismissed.” Constance’s experience in the ED is not uncommon among people with SCD, a condition that causes abnormal, sickle-shaped red blood cells that can block blood flow and limit the amount of oxygen getting to the body’s tissues and organs.   Related story

Pain is the major complication for the approximately 100,000 individuals with sickle cell disease (SCD) in the United States. Although opioid analgesics are the mainstay therapy for SCD pain, little is known about the use of self-managed modalities (e.g., relaxation) and the effects of relaxation on pain, stress, and autonomic responses in patients with SCD.This pre-post randomized controlled trial was conducted to: 1) determine protocol feasibility: (a) issues of Pentablet computer use for relaxation intervention delivery; (b) acceptability of study procedures; and (c) percentage of missing data); and 2) estimate the size of the relaxation intervention effects on pain and stress and physiologic markers of relaxation (respiration, pulse, and skin temperature [mediators]).Patients (N = 30, mean age 34.9 ± 10.4 years [22–59 years], 100% Non-Hispanic, 53% male) enrolled between June 2016 and March 2017 were randomized to Experimental (12 min Relaxation video clip) or Control (12 min SCD discussion) groups. Physiological markers and questionnaires (pain, stress) were completed before and after the intervention. Data were analyzed using the statistical software R.All participants signing the consent completed the study; 93% of the 30 participants completed over 90% of the questionnaire items; 89% of control and 92% of experimental groups reported that the intervention was “Not hard at all;” and 83% of experimental group reported that they liked the intervention whereas 44% of control group did. Regression results controlling for baseline measure indicate a trend for positive relaxation intervention effects on pain (p = .09) and stress (p = .08). Relaxation indicators including respiration (p = .23), pulse (p = .79), and skin temperature (p = .60) were not significantly different between the two groups.The study was feasible and the relaxation intervention was promising in reducing pain and stress. Future studies are warranted to test efficacy of the relaxation intervention and its mechanism in this population suffering with chronic disabling pain.  Abstract source

OBJECTIVES: Sickle cell disease (SCD) pain and hospitalizations increase during adolescence and adolescents with SCD may be at-risk for experiencing health-related stigma, which may result in poor health outcomes. This study examined relations among health-related stigma, pain interference, social support, quality of life (QOL), and hospital outcomes (ie, loneliness, pain reduction, and length of stay [LOS]) in adolescents hospitalized with SCD pain.   MATERIALS AND METHODS: Twelve- to 18-year-old adolescents (N=92) hospitalized with SCD pain completed measures of stigma, pain interference, social support, QOL, and state loneliness. Reduction of pain intensity during hospitalization and LOS were collected from medical chart review.   RESULTS: Higher stigma was associated with higher pain interference, lower QOL, more loneliness, and less pain reduction in the hospital. Pain interference was positively associated with LOS.   DISCUSSION: These preliminary findings highlight the importance of assessing and addressing SCD-related stigma and pain interference in adolescents hospitalized for SCD pain as these factors may influence treatment outcomes.   Abstract source

Pain is a clinical hallmark of sickle cell disease (SCD), and is rarely optimally managed. Cognitive-behavioral therapy (CBT) for pain has been effectively delivered through the Internet in other pediatric populations. We tested feasibility and acceptability of an Internet-delivered CBT intervention in 25 adolescents with SCD (64% female, mean age=14.8 y) and their parents randomized to Internet CBT (n=15) or Internet Pain Education (n=10).Participants completed pretreatment/post treatment measures. Eight dyads completed semistructured interviews to evaluate treatment acceptability. Feasibility indicators included recruitment and participation rates, engagement and adherence to intervention, and completion of outcome measures.In total, 87 referrals were received from 9 study sites; our recruitment rate was 60% from those families approached for screening. Among participants, high levels of initial intervention engagement (>90%), and adherence (>70%) were demonstrated. Most participants completed post treatment outcome and diary measures (>75%). Retention at post treatment was 80%. High treatment acceptability was reported in interviews.Our findings suggest that Internet-delivered CBT for SCD pain is feasible and acceptable to adolescents with SCD and their parents. Engagement and adherence were good. Next steps are to modify recruitment plans to enhance enrollment and determine efficacy of Internet CBT for SCD pain in a large multisite randomized controlled trial.  Abstract source

Sickle cell anemia is an inherited systemic hemoglobinopathy that affects hemoglobin production in red blood cells, leading to early morbidity and mortality. It is caused by a homozygous nucleotide substitution (c.20A>T) in the β-globin gene (HBB) that changes a glutamic acid to a valine in the protein.We present a case report of a fertile couple, both carriers of the sickle cell anemia mutation, with one affected daughter. Six cycles of assisted reproductive techniques were performed, resulting in 53 embryos in cleavage stage. Each embryo was biopsied and analyzed for pre-implantation genetic diagnosis (PGD) by fluorescent polymerase chain reaction, using polymorphic markers of the region of interest followed by capillary electrophoresis in an automated genetic analyzer.HLA Compatible and normal embryos for the mutation represented 3 (5.66%); while the carriers and compatible 6 (11.32%); therefore, embryos matching those of the affected daughter represented 9 (16.98%). A selected embryo in blastocyst stage was transferred, resulting in a healthy male newborn, who had the umbilical cord blood cells collected and stored.The affected daughter was immunosuppressed and received transplanted cells from the umbilical cord blood of her brother; the treatment was successful. Embryo selection using PGD technologies represent the most effective treatment plan for parents who want to have a healthy child, and it could cure another child already affected by inherited hemoglobinopathy.  Abstract source Full text

Sickle cell disease (SCD) is an inherited red blood cell disorder that occurs worldwide and results in significant morbidity and mortality. In addition to affected children who are born in the US, an increasing number of children with SCD are migrating to the US with their families or through international adoption. Children arriving as immigrants or refugees have unique medical and psychosocial challenges that require a multidisciplinary team approach which takes into account the family's primary language, culture, and health beliefs. This review focuses on the special challenges for children with SCD who emigrate from sub-Saharan Africa to the US.   Abstract source