Serial phlebotomy was performed on sixty children with sickle cell anaemia, stroke and transfusional iron overload randomized to hydroxycarbamide in the Stroke With Transfusions Changing to Hydroxyurea trial. There were 927 phlebotomy procedures with only 33 adverse events, all of which were grade 2. Among 23 children completing 30 months of study treatment, the net iron balance was favourable (-8·7 mg Fe/kg) with significant decrease in ferritin, although liver iron concentration remained unchanged. Therapeutic phlebotomy was safe and well-tolerated, with net iron removal in most children who completed 30 months of protocol-directed treatment. Abstract source Full text Full text (PMC)

BACKGROUND: Pregnancies in women with sickle cell disease (SCD) are known to have high rates of maternal and fetal mortality and morbidity. Given these pregnancy-associated problems for women with SCD, advice both about pregnancy planning and about effective contraception are of paramount importance. This study sought to discover the contraception methods used by women with SCD, what complications women with SCD encounter with contraception, and their experiences of pre-pregnancy counselling and pregnancy planning, and how such issues may have changed over the past two decades. METHOD: The study was a multicentre, interview-based, cross-sectional study. Interviews were carried out with 102 women with SCD, in north and central London during 2010, concerning their current and previous contraceptive use, their pregnancy history, their menstrual history, and the advice they received concerning pregnancy planning and contraception. Patient information was anonymised and ethical approval was obtained. These data were compared with data from a similar study undertaken in 1993. RESULTS: There were significant differences in a number of key areas: the number of unplanned pregnancies decreased from 64% in 1993 to 53% in 2010. The number of women with SCD who were advised not to become pregnant also fell, from 36% to 15%. The use of combined oral contraceptive pills declined, from 45% of the women in 1993 to 31% in 2010. Conversely the use of depot medroxyprogesterone acetate contraception (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) both increased. CONCLUSIONS: Significant changes in the contraceptive methods used by women with SCD are demonstrated in the London population. LNG-IUS use in SCD has not been investigated before. There has been an encouraging decrease in the number of women with SCD who are advised not to become pregnant, perhaps reflecting an improvement in their overall health. Although the number of unplanned pregnancies has fallen, it remains high - emphasising the continuing need for women with SCD to have access to informed advice about pregnancy-associated issues and contraception. Abstract source Full text

Background Sickle cell disease (SCD) is one of the most common causes of stroke in children worldwide. Based on the results of the Stroke Prevention Trial in Sickle Cell Anemia (STOP), annual transcranial Doppler ultrasound (TCD) screening for affected children is standard practice. However, the need for TCD surveillance programs could override the accuracy of the screening, affecting the correct stratification of stroke risk and subsequent clinical management of the target population. Aims To shed light on this issue, a systematic review of the literature on TCD screening for children and adolescents with SCD was carried out (CRD42016050549), according to a list of clinically relevant questions, with a particular focus on screening practices in European countries. Quality of the evidence was rated using the grading of recommendations assessment, development and evaluation. Summary of review Thirty-three studies published in English or French were included (5 randomized controlled trials, 8 experimental non-randomized, and 20 observational studies). The quality of the retrieved evidence ranged between low and high, but was rated as moderate or high most of the times. TCD is effective as a screening tool for the primary prevention of stroke in SCD children. There is no high-quality evidence on the effectiveness of alternative screening methods, such as imaging-TCD with or without angle correction or magnetic resonance angiography. No evidence was found on effectiveness of the screening on children on hydroxyurea and with genotypes other than HbSS and HbS/β0. No European data were found on screening rates or adherence of screening practices to the STOP protocol. Conclusions High-quality studies on alternative screening methods that are currently used in real-world practice, and on screening applicability to specific subgroups of patients are urgently needed. Considering the low awareness of the disease in European countries and the lack of data on screening practices and adherence, clinicians need up-to-date guidelines for more uniform and evidence-based surveillance of children with SCD. Abstract source Full text

BACKGROUND: Avascular necrosis of bone is a frequent and severe complication of sickle cell disease and its treatment is not standardised. This is an update of a previously published Cochrane Review. OBJECTIVES: To determine the impact of any surgical procedure compared with other surgical interventions or non-surgical procedures, on avascular necrosis of bone in people with sickle cell disease in terms of efficacy and safety. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Additional trials were sought from the reference lists of papers identified by the search strategy.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 27 May 2016. SELECTION CRITERIA: Randomized clinical trials comparing specific therapies for avascular necrosis of bone in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: Each author independently extracted data and assessed trial quality. Since only one trial was identified, meta-analysis was not possible. MAIN RESULTS: One trial (46 participants) was eligible for inclusion. After randomization eight participants were withdrawn, mainly because they declined to participate in the trial. Data were analysed for 38 participants at the end of the trial. After a mean follow up of three years, hip core decompression and physical therapy did not show clinical improvement when compared with physical therapy alone using the score from the original trial (an improvement of 18.1 points for those treated with intervention therapy versus an improvement of 15.7 points with control therapy). There was no significant statistical difference between groups regarding major complications (hip pain, risk ratio 0.95 (95% confidence interval 0.56 to 1.60; vaso-occlusive crises, risk ratio 1.14 (95% confidence interval 0.72 to 1.80; very low quality of evidence); and acute chest syndrome, risk ratio 1.06 (95% confidence interval 0.44 to 2.56; very low quality of evidence)). This trial did not report results on mortality or quality of life. AUTHORS' CONCLUSIONS: We found no evidence that adding hip core decompression to physical therapy achieves clinical improvement in people with sickle cell disease with avascular necrosis of bone compared to physical therapy alone. However, we highlight that our conclusion is based on one trial with high attrition rates. Further randomized controlled trials are necessary to evaluate the role of hip-core depression for this clinical condition. Endpoints should focus on participants' subjective experience (e.g. quality of life and pain) as well as more objective 'time-to-event' measures (e.g. mortality, survival, hip longevity). The availability of participants to allow adequate trial power will be a key consideration for endpoint choice. Abstract source Full text

Although the root cause of sickle cell disease is the polymerization of hemoglobin S (HbS) to form fibers that make red cells less flexible, most drugs currently being assessed in clinical trials are targeting the downstream sequelae of this primary event. Less attention has been devoted to investigation of the multiple ways in which fiber formation can be inhibited. In this article, we describe the molecular rationale for 5 distinct approaches to inhibiting polymerization and also discuss progress with the few antipolymerization drugs currently in clinical trials. Abstract source Full text Full text (PMC)

Acute chest syndrome is a frequent cause of acute lung disease in children with sickle-cell disease. Asthma is common in children with sickle-cell disease and is associated with increased incidence of vaso-occlusive pain events, acute chest syndrome episodes, and earlier death. Risk factors for asthma exacerbation and an acute chest syndrome episode are similar, and both can present with shortness of breath, chest pain, cough, and wheezing. Despite overlapping risk factors and symptoms, an acute exacerbation of asthma or an episode of acute chest syndrome are two distinct entities that need disease-specific management strategies. Although understanding has increased about asthma as a comorbidity in sickle-cell disease and its effects on morbidity, substantial gaps remain in knowledge about best management. Abstract source Full text Full text (PMC)

BACKGROUND: Little is known about the rate of, and factors affecting, progression of talar osteonecrosis related to sickle cell disease. Adult patients with sickle cell disease who presented with hip osteonecrosis were evaluated for talar osteonecrosis with radiographs and magnetic resonance imaging (MRI). Forty-five of them (75 tali) were diagnosed with talar osteonecrosis, and this group was evaluated for factors influencing the progression of the disease. METHODS: Forty-five patients with sickle cell disease and osteonecrosis of the talus were identified with radiographs and MRI between 1985 and 1995. Seven of these patients were homozygous for hemoglobin S (S/S genotype), 26 had hemoglobin S/hemoglobin C, and 12 had hemoglobin S/beta-thalassemia. The talar osteonecrosis was graded with radiographs and MRI. The patients were followed with clinical examination and radiographs every 6 months until talar collapse and every year after the collapse. RESULTS: The osteonecrosis was unilateral in 15 patients and bilateral in 30 at the time of the initial examination. Forty-five ankles were asymptomatic and 30 were symptomatic at the initial evaluation. MRI performed at the time of the most recent follow-up, and compared with MRI performed at diagnosis, did not show partial or total regression of the osteonecrosis in any of the patients, even those with asymptomatic stage-I osteonecrosis. At the time of the most recent follow-up (mean, 20 years; range, 15 to 25 years), pain and collapse had developed in all except 12 ankles. The stage of the osteonecrosis at the initial visit, pain, the genotype of the sickle cell disease, and the extent and location of the lesion in the talus were risk factors for progression of the disease. CONCLUSIONS: In the majority of the patients with sickle cell disease, osteonecrosis of the talus should be expected to show relevant clinical and radiographic evidence of progression over a long period. Abstract source Full text

BACKGROUND: Community health workers (CHW) are increasingly recognized as a strategy to improve health outcomes for the underserved with chronic diseases but has not been formally explored in adolescents with sickle cell disease (SCD). SCD primarily affects African American, Hispanic and other traditionally underserved populations. Hydroxyurea (HU), an oral, once-daily medication, is the only approved therapeutic drug for sickle cell disease and markedly reduces symptoms, morbidity and mortality and improves quality of life largely by increasing hemoglobin F blood levels. This paper presents the rationale, study design and protocol for an open label randomized controlled trial to improve parent-youth partnerships in self-management and medication adherence to HU in adolescents with SCD. METHODS/DESIGN: A CHW intervention augmented by text messaging was designed for adolescents with SCD ages 10-18years and their parents to improve daily HU adherence. Thirty adolescent parent dyads will be randomized with 2:1 intervention group allocation. Intervention dyads will establish a relationship with a culturally aligned CHW to identify barriers to HU use, identify cues to build a habit, and develop a dyad partnership to improve daily HU adherence and achieve their individualized "personal best" hemoglobin F target. Intervention feasibility, acceptability and efficacy will be assessed via a 2-site trial. Outcomes of interest are HU adherence, dyad self-management communication, quality of life, and resource use. DISCUSSION: Despite known benefits, poor HU adherence is common. If feasible and acceptable, the proposed intervention may improve health of underserved adolescents with SCD by enhancing long-term HU adherence. Abstract source Full text Full text (PMC)

Elevated tricuspid regurgitant jet velocity (TRJV) is a surrogate measure of pulmonary hypertension (PH) in persons with sickle cell disease (SCD). We sought to estimate the burden of PH in people living with sickle cell disease based on TRJV. From 2000 to 2015, we searched electronic databases for eligible publications and included 29 studies (n = 5358 persons). We used random effects modeling to determine the pooled estimate of elevated TRJV. The overall pooled prevalence of elevated TRJV was 23.5 %(95 % CI 19.5-27.4) in persons with SCD. The pooled prevalence of elevated TRJV in children and adults with SCD was 20.7 % (95 % CI 15.7--25.6) and 24.4 % (95 % CI 18.4-30.4), respectively. TRJV is prevalent among adults and children with SCD. Our finding support international recommendations that call for screening for PH in SCD patients. Abstract source Full text

Tobacco smoke exposure has been associated with more frequent hospitalizations in children with sickle cell disease (SCD), but previous studies have not quantified the exposure by objective methods. We enrolled 50 children and young adults with SCD in a retrospective and prospective cohort study and quantified tobacco smoke exposure by objective (salivary cotinine) and survey measures. We used a multivariable negative binomial regression model to evaluate the association between salivary cotinine and hospital admissions. Forty-five percent (22/49) of participants had significant elevation of salivary cotinine (≥ 0.5 ng/ml). The incidence risk ratio (IRR) for hospital admission for those with elevated cotinine was 3.7 (95% CI 1.8-8). Those exposed to secondhand smoke but not primary smokers (cotinine between 0.5 and 10 ng/ml) had a similarly increased risk of hospitalization [IRR 4.3 (95% CI 1.8-10)]. We show that an objective measure of tobacco smoke exposure, salivary cotinine, is strongly associated with the rate of hospital admissions in children and young adults with SCD. This association underscores the importance of screening for tobacco smoke exposure in people with SCD. Further investigation is warranted to determine the mechanisms of and to evaluate interventions to decrease tobacco smoke exposure. Abstract source Full text