Sickle cell disease (SCD) is associated with impaired vascular function and progressive vaso-occlusive injury to bones. We used the Nationwide Inpatient Sample to identify all THA and TKA admissions between 1998 and 2010. After controlling for patient age, gender, insurance, race, and comorbidities, the risk of complication among admissions with SCD was 152% higher (P<0.001) for THA and 137% higher (P=0.001) for TKA. Patients with SCD had a length of stay that was 42% longer (P<0.001) for THA and 20% longer for TKA (P<0.001), and hospital charges that were 19% higher (P<0.001) for THA and 16% higher (P=0.001) for TKA. Orthopedic surgeons should counsel potential THA and TKA candidates with SCD of these risks prior to admission. Abstract source Full text

INTRODUCTION: Advances in primary prophylaxis have resulted in improved outcomes for patients with sickle cell anemia (SCA; i.e., hemoglobin SS- and Sβ(0)-thalassemia). Standard prophylactic measures include a first pneumococcal polysaccharide vaccine (PPV) and transcranial Doppler ultrasound (TCD) at age 2 years. Though efficacious, evidence suggests that delivery of these interventions is suboptimal. This study reports adherence to these measures and examines concordance across various data sources, using Registry and Surveillance for Hemoglobinopathies project data. METHODS: Retrospective database and SCA center chart review identified children with SCA aged 24-36 months between January 1, 2004, and December 31, 2008. PPV and TCD administration were determined through Medicaid and Children's Health Insurance Program administrative claims data, medical record review, and Georgia Registry of Immunization Transaction and Services. Analysis was conducted in 2015. RESULTS: A total of 125 children met inclusion criteria. Forty-five (36.0%) children had documentation of both interventions, whereas 19 (15.2%) had no documentation of either intervention. Sixty-one (48.8%) children obtained only one intervention. Of these, more were likely to have had PPV than TCD (77.0% vs 23.0%, respectively, p<0.001). Agreement between claims data and medical record review was moderate for PPV (κ=0.55) and substantial for TCD (κ=0.74). CONCLUSIONS: No single, reliable data source for tracking standard of care for children with SCA statewide was found. According to study data, prophylaxis measures were not universally implemented during the surveillance period. Further research is needed to adequately track changes over time, determine risk groups, and develop methods of evaluating important metrics. Abstract source Full text Full text (PMC)

BACKGROUND: The up-regulation of P-selectin in endothelial cells and platelets contributes to the cell-cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell-related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease. METHODS: In this double-blind, randomized, placebo-controlled, phase 2 trial, we assigned patients to receive low-dose crizanlizumab (2.5 mg per kilogram of body weight), high-dose crizanlizumab (5.0 mg per kilogram), or placebo, administered intravenously 14 times over a period of 52 weeks. Patients who were receiving concomitant hydroxyurea as well as those not receiving hydroxyurea were included in the study. The primary end point was the annual rate of sickle cell-related pain crises with high-dose crizanlizumab versus placebo. The annual rate of days hospitalized, the times to first and second crises, annual rates of uncomplicated crises (defined as crises other than the acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism) and the acute chest syndrome, and patient-reported outcomes were also assessed. RESULTS: A total of 198 patients underwent randomization at 60 sites. The median rate of crises per year was 1.63 with high-dose crizanlizumab versus 2.98 with placebo (indicating a 45.3% lower rate with high-dose crizanlizumab, P=0.01). The median time to the first crisis was significantly longer with high-dose crizanlizumab than with placebo (4.07 vs. 1.38 months, P=0.001), as was the median time to the second crisis (10.32 vs. 5.09 months, P=0.02). The median rate of uncomplicated crises per year was 1.08 with high-dose crizanlizumab, as compared with 2.91 with placebo (indicating a 62.9% lower rate with high-dose crizanlizumab, P=0.02). Adverse events that occurred in 10% or more of the patients in either active-treatment group and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain. CONCLUSIONS: In patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crises than placebo and was associated with a low incidence of adverse events. (Funded by Selexys Pharmaceuticals and others; SUSTAIN ClinicalTrials.gov number, NCT01895361 .). Abstract source Full text Full text (PMC)

In spite of significant strides in the treatment of sickle cell disease (SCD), SCD crises are still responsible for high morbidity and early mortality. While most patients initially seek care in the acute setting for a seemingly uncomplicated pain episode (pain crisis or vaso-occlusive crisis), this initial event is the primary risk factor for potentially life-threatening complications. The pathophysiological basis of these illnesses is end-organ ischemia and infarction combined with the downstream effects of hemolysis that results from red blood cell sickling. These pathological changes can occur acutely and lead to a dramatic clinical presentation, but are frequently superimposed over a milieu of chronic vasculopathy, immune dysregulation, and decreased functional reserve. In the lungs, acute chest syndrome is a particularly ominous lung injury syndrome with a complex pathogenesis and potentially devastating sequelae, but all organ systems can be affected. It is, therefore, critical to understand the SCD patients' susceptibility to acute complications and their risk factors so that they can be recognized promptly and managed effectively. Blood transfusions remain the mainstay of therapy for all severe acute crises. Recommendations and indications for the safest and most efficient implementation of transfusion strategies in the critical care setting are therefore presented and discussed, together with their pitfalls and potential future therapeutic alternatives. In particular, the importance of extended phenotypic red blood cell matching cannot be overemphasized, due to the high prevalence of severe complications from red cell alloimmunization in SCD. Abstract source Full text

PURPOSE: To correlate macular findings on spectral domain optical coherence tomography (SDOCT) and optical coherence tomography angiography (OCTA) with quantitative ischemic index calculations on ultra-wide-field fluorescein angiography (UWFFA) in patients with sickle cell retinopathy.METHODS: In this retrospective case series, SDOCT, OCTA, and UWFFA images of patients with sickle cell retinopathy were evaluated. Eyes were staged based on the Goldberg classification of proliferative sickle cell retinopathy. Focal areas of macular thinning were assessed on SDOCT, macular vessel density was derived from OCTA, and peripheral ischemic index was calculated from UWFFA.RESULTS: Eighteen eyes of 10 patients were included. Mean age was 36.8 ± 16.8 years, and 6 patients (11 eyes) were SS, 3 patients (5 eyes) were SC, and 1 patient (2 eyes) was Sβ thalassemia in hemoglobin electrophoresis. Abnormal macular findings included inner retinal atrophy in 11 eyes (61%) on SDOCT, vascular remodeling and nonperfusion in the superficial and deep retinal capillary plexus in 12 eyes (67%) on OCTA, and macular microvascular abnormalities in 9 eyes (50%) on UWFFA. Sickle cell retinopathy Stage I was identified in 4 eyes (22.2%), Stage II in 8 eyes (44.4%), and Stage III in 6 eyes (33.3%). Mean ischemic index was 14.1 ± 9.1%. Ischemic index was significantly correlated with hemoglobinopathy subtype (23.7 ± 9.8%, 9.3 ± 5.4%, and 16.3 ± 3.2%, for SC, SS, and Sβ thalassemia disease, respectively), stage of sickle cell retinopathy (22.5 ± 9.2%, 12.5 ± 4.9%, and 4.5 ± 0.73% for Stages III, II, and I, respectively), and presence of retinal thinning on SDOCT (17.4 ± 9.7% vs. 8.8 ± 5.1%, respectively).CONCLUSION: Multimodal imaging can provide a more complete description of the microvascular and structural alterations associated with sickle retinopathy. The correlation between the severity of peripheral nonperfusion and stage and subtype of retinopathy suggests that UWF imaging may be a useful tool in the evaluation of these patients. Abstract source Full text

Patients with sickle cell disease are at high risk for chronic hepatitis C infection. Prior treatment has been limited due to the use of ribavirin causing hemolytic anemia and interferon causing cytopenias. We demonstrate the safety and efficacy of fixed dose combination, ledipasvir and sofosbuvir for 12 weeks in this population. Abstract source Full text

Red blood cell (RBC) alloimmunization is a major complication of transfusion therapy in sickle cell disease (SCD). Identification of high-risk patients is hampered by lack of studies that take the cumulative transfusion exposure into account. In this retrospective cohort study among previously non-transfused SCD patients in the Netherlands, we aimed to elucidate the association between the cumulative transfusion exposure, first alloimmunization and independent risk factors. A total of 245 patients received 11 952 RBC units. Alloimmunization occurred in 43 patients (18%), half of them formed their first alloantibody before the 8th unit. In patients with exposure to non-extended matched transfusions (ABO and RhD) the cumulative alloimmunization risk increased up to 35% after 60 transfused units. This was significantly higher compared to a general transfused population (HR 6.6, CI 4.2-10.6). Receiving the first transfusion after the age of 5 was an independent risk factor for alloimmunization (HR 2.3, CI 1.0-5.1). Incidental, episodic transfusions in comparison to chronic scheme transfusions (HR 2.3, CI 0.9-6.0), and exposure to non-extended matched units in comparison to extended matching (HR 2.0, CI 0.9-4.6) seemed to confer a higher alloimmunization risk. The majority of first alloantibodies are formed after minor transfusion exposure, substantiating suggestions of a responder phenotype in SCD and stressing the need for risk factor identification. In this study, older age at first transfusion, episodic transfusions and non-extended matched transfusions appeared to be risk factors for alloimmunization. Abstract source Full text

BACKGROUND: Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review. OBJECTIVES: To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 28 November 2015. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS: Both authors independently selected studies for inclusion, assessed study quality and extracted data. MAIN RESULTS: Of the 51 studies identified, three met the inclusion criteria. The first study tested the effectiveness of zinc sulphate to prevent sickle cell-related crises in a total of 145 participants and showed a significant reduction in painful crises over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15). However, analysis was restricted due to limited statistical data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in the study.The second study was a Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo. Compared to the placebo group the high dose senicapoc showed significant improvement in change in hemoglobin level, number and proportion of dense red blood cells, red blood cell count and indices and hematocrit. The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups. A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises. AUTHORS' CONCLUSIONS: While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red cell survival (depending on dose), this did not lead to fewer painful crises.We will continue to run searches to identify any potentially relevant trials; however, we do not plan to update other sections of the review until new trials are published. Abstract source Full text

BACKGROUND: The majority of available studies have shown that children with sickle cell disease (SCD) have a higher risk of depressive symptoms than those without. The present study aimed to: assess the prevalence of depression in a sample of children with SCD; evaluate the association between disease severity, social support and depression, and the combined and/or singular effect on health-related quality of life (HRQL) in children with SCD; and show the predictive value of social support and disease severity on depression. METHODS: A total of 120 children were included in the study, 60 (group I) with SCD and 60 matched, healthy control children (group II). Depression was assessed in both groups using the Children's Depression Inventory (CDI) and the Children's Depression Inventory-Parent (CDI-P). Children with CDI and CDI-P scores of more than 12 were interviewed for further assessment of depression using the Diagnostic Interview Schedule for Children Version IV (DISC-IV). The Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales (PedsQL 4.0) was used to assess HRQL in both groups, and social support was measured with the Child and Adolescent Social Support Scale (CASSS). RESULTS: Eight (13%) of the 60 children with SCD had CDI and CDI-P scores of more than 12 (CDI mean score 14.50 ± 1.19, CDI-P mean score 14.13 ± 1.12), and were diagnosed as having clinical depression using the diagnostic interview DISC-IV. For group I, HRQL was poor across all PedsQL 4.0 domains in both self- and parent-reports (P < 0.001) compared with group II. A higher level of parent support was a significantly associated with decreased depressive symptoms, demonstrated by lower CDI scores. Better quality of life was shown by the associated higher total PedsQL 4.0 self-scores of children with SCD (B = -1.79, P = 0.01 and B = 1.89, P = 0.02 respectively). CONCLUSIONS: The present study demonstrates that higher levels of parent support were significantly associated with decreased depressive symptoms and better quality of life in children with SCD. Interventions focused on increasing parent support may be an important part of treatment for depression in children with SCD. Abstract source Full text Full text (PMC)

Previous reports demonstrated that patients with sickle cell disease (SCD) experience pain on more than half of the observed days. Yet, these high incidences do not seem to match observations in our population. In this prospective cohort study, we aimed to assess the frequency and characteristics of daily, self-reported pain among adult SCD patients in the Netherlands. Consecutive patients were enrolled during routine outpatient visits and followed up to 6 months. A total of 55 patients completed 5,982 diary observation days. Median age was 27 years (IQR 23-43). Patients reported SCD related pain on 17% of the observed days; on 13% of these days this pain was not defined as a painful crisis, while 3% was reported as a painful crisis but managed at home, and on 1% of the observed days patients were admitted to the hospital. Analgesics were used on 52% of days with pain with a relatively infrequent use of oral opioids (9% of pain days). This first European study on pain in SCD indicates that pain appears to be significantly less frequent in our population as compared to previous study cohorts from the United States, and may be more representative for current SCD populations in other Western countries. Besides a more widespread use of hydroxycarbamide in modern disease management, differences in organization and accessibility of healthcare between countries may also explain this discrepancy. Abstract source Full text