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Objective: Chronic hemolysis is a hallmark of sickle cell disease (SCD) and a driver of vasculopathy; however, the mechanisms contributing to hemolysis remain incompletely understood. Although XO (xanthine oxidase) activity has been shown to be elevated in SCD, its role remains unknown. XO binds endothelium and generates oxidants as a byproduct of hypoxanthine and xanthine catabolism. We hypothesized that XO inhibition decreases oxidant production leading to less hemolysis. Approach and Results: Wild-type mice were bone marrow transplanted with control (AA) or sickle (SS) Townes bone marrow. After 12 weeks, mice were treated with 10 mg/kg per day of febuxostat (Uloric), Food and Drug Administration–approved XO inhibitor, for 10 weeks. Hematologic analysis demonstrated increased hematocrit, cellular hemoglobin, and red blood cells, with no change in reticulocyte percentage. Significant decreases in cell-free hemoglobin and increases in haptoglobin suggest XO inhibition decreased hemolysis. Myographic studies demonstrated improved pulmonary vascular dilation and blunted constriction, indicating improved pulmonary vasoreactivity, whereas pulmonary pressure and cardiac function were unaffected. The role of hepatic XO in SCD was evaluated by bone marrow transplanting hepatocyte-specific XO knockout mice with SS Townes bone marrow. However, hepatocyte-specific XO knockout, which results in >50% diminution in circulating XO, did not affect hemolysis levels or vascular function, suggesting hepatocyte-derived elevation of circulating XO is not the driver of hemolysis in SCD. Conclusions: Ten weeks of febuxostat treatment significantly decreased hemolysis and improved pulmonary vasoreactivity in a mouse model of SCD. Although hepatic XO accounts for >50% of circulating XO, it is not the source of XO driving hemolysis in SCD.

Objective: To identify the costs of treating leg ulcers due to sickle cell disease from the perspective of the Unified Health System. Method: An observational, descriptive, cost-effective economic assessment study conducted in a single center with ulcer patients. The data collected were extracted from the participant’s medical records and recorded in a form prepared for this purpose. The cost of the products used in ulcer treatment was provided by the Solicitation/Purchasing Section and Pharmacy Sector of the study institution. The variables studied were ulcer area, number and interval between visits, patient’s length of stay in the service, materials used in each visit, and the number of nurse appointments. Results: The sample consisted of 29 patients. The average initial area of ulcers was 14.47 cm2, 79% of the cases had complete epithelialization in an average time of 8.02 months, with an average cost of R$ 1,288.06. The average cost to reduce 1 cm2 of the lesion area was R$ 102.20. Silver activated carbon coating was the most cost-effective treatment. Conclusion: The average cost for complete healing of a sickle cell ulcer with an average area of 14.95 cm2 was R$ 1,288.06. Resumen Objetivo: Identificar los costos desembolsados con el tratamiento de la úlcera de pierna consecuente de la enfermedad de células falciformes bajo la perspectiva del Sistema Único de Salud. Método: Estudio observacional, descriptivo, de evaluación económica del costo-efectividad, llevado a cabo en un centro único, con pacientes portadores de úlcera. Los datos recogidos fueron extraídos de la ficha del participante y registrados en formulario confeccionado para esta finalidad. El costo de los productos utilizados en el tratamiento de la úlcera lo abonaron la Sección de Licitaciones/Compras y el Sector de Farmacia del centro del estudio. Las variables estudiadas fueron: área de la úlcera, número e intervalo entre las atenciones, tiempo de estancia del paciente en el servicio, materiales utilizados en cada atención, número de consultas del enfermero. Resultados: La muestra estuvo compuesta de 29 pacientes. El área inicial media de las úlceras fue 14,47 cm2, el 79% de los casos tuvieron completa epitelización en tiempo medio de 8,02 meses, con costo medio de R$ 1.288,06. Para reducir 1 cm2 del área de la lesión, el costo medio fue de R$ 102,20. La cobertura de carbón activado con plata tuvo el mejor costo-efectividad. Conclusión: El costo medio para la completa cicatrización de una úlcera por enfermedad falciforme con área media de 14,95 cm2 fue de R$ 1.288,06. Resumo Objetivo: Identificar os custos despendidos com o tratamento da úlcera de perna decorrente da doença falciforme na perspectiva do Sistema Único de Saúde. Método: Estudo observacional, descritivo, de avaliação econômica do custo-efetividade, realizado em um centro único, com pacientes portadores de úlcera. Os dados coletados foram extraídos do prontuário do participante e registrados em formulário elaborado para esta finalidade. O custo dos produtos utilizados no tratamento da úlcera foi provido pela Seção de Licitações/Compras e Setor de Farmácia da instituição do estudo. As variáveis estudadas foram área da úlcera, número e intervalo entre os atendimentos, tempo de permanência do paciente no serviço, materiais utilizados em cada atendimento, número de consultas do enfermeiro. Resultados: A amostra foi composta por 29 pacientes. A área inicial média das úlceras foi 14,47 cm2, 79% dos casos tiveram completa epitelização em tempo médio de 8,02 meses, com custo médio de R$ 1.288,06. Para reduzir 1 cm2 da área da lesão o custo médio foi de R$ 102,20. A cobertura de carvão ativado com prata teve o melhor custo-efetividade. Conclusão: O custo médio para a completa cicatrização de uma úlcera por doença falciforme com área média de 14,95 cm2 foi de R$ 1.288,06.

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Die Untersuchung des Blutausstrichs ist nicht nur in der Differenzialdiagnostik hamatologischer Erkrankungen bedeutsam, sondern kann auch Hinweise auf allgemeine internistische Erkrankungen, Infektionen, hereditare Erkrankungen oder Vergiftungen geben. Durch die systematische Analyse des Blutausstrichs auf thrombozytare, erythrozytare und leukozytare Veranderungen kann die Blutbilduntersuchung entscheidend zur Diagnosestellung beitragen. Hierbei konnen unter Berucksichtigung der entsprechenden Klinik auch Hinweise auf seltene Erkrankungen gewonnen werden.

We have entered an era of exploding interest in therapeutics for sickle cell disease. The expansion in our understanding of sickle cell disease pathophysiology has enhanced the range of potential therapeutic targets. From induction of fetal hemoglobin to antiadhesion molecules, we are potentially on the cusp of making life-altering modifications for individuals with sickle cell disease. This disease population cannot afford to let the current momentum wane. Studies exploring combinations of therapies affecting multiple steps in the pathophysiology and exploring novel and clinically relevant outcomes are incumbent.

Sickle cell disease (SCD) is associated with episodic illnesses, multi-systemic affectations and end-organs damages. Otolaryngological related complications are not unexpected. Studies on the overall Otolaryngological pathologies in children with SCD relative to their non-SCD counterparts are scanty in Nigeria. We hypothesized that children with SCD are likely to have more otological burdens than their non-SCD counterparts. Thus, we embarked on this study to describe and compare the overall ear diseases burdens seen in children with sickle cell disease relative to their non-SCD counterparts.A cross-sectional study of otologic diseases among children with SCD and their non-SCD counterparts attending the paediatrics and otolaryngological clinics of a Nigerian tertiary institution was conducted.Overall, 80 (47.62%) of the 168 ears of SCD patients compared to 37 (22.02%) of the 168 ears of their non-SCD counterparts were affected by diseases (p 0.0001). The diseases were Wax, Otitis Media with Effusion, Suppurative Otitis Media, Otosclerosis and Sensorineural Hearing Loss (SNHL). There was a significant difference in the prevalence of SNHL and solitary otosclerosis between the SCD patients and their non-SCD counterparts (P 0.05) respectively. Both the Haemoglobin concentration and HbF did not discriminate between the SCD participants with or without SNHL (P 0.05).This study showed that otological burdens are more prevalent in children with SCD than the non-SCD population. The microbiological peculiarity of suppurative otitis media (SOM) among participants stresses the need for concerted efforts at preventing SOM in SCD children. There is need for special Otolaryngological care for SCD children.

Sickle cell disease (SCD) is a devastating monogenic disorder that presents as a multisystem illness and affects approximately 100,000 individuals in the United States alone. SCD management largely focuses on primary prevention, symptomatic treatment and targeting of hemoglobin polymerization and red blood cell sickling. Areas covered: This review will discuss the progress of SCD over the last few decades, highlighting some of the clinical (mainly cerebrovascular) and psychosocial challenges of SCD in the United States. In addition, focus will also be made on the evolving science and management of this inherited disease. Expert commentary: Until recently hydroxyurea (HU) has been the only FDA approved therapy for SCD. However, advancing understanding of SCD pathophysiology has led to multiple clinical trials targeting SCD related thrombo-inflammation, abnormal endothelial biology, increased oxidant stress and sickle cell mutation. Yet, despite advancing understanding, available therapies are limited. SCD also imposes great psychosocial challenges for the individual and the affected community, which has previously been under-recognized. This has created a pressing need for complementary adjuvant therapies with repurposed and novel drugs, in addition to the establishment of comprehensive clinics focusing on both the medical treatment and the psychosocial issues associated with SCD.

Objective: To identify the application of Orem’s self-care theory in patients with sickle cell anemia (SCA) at a regional hematology center. Methods: It is a study of a descriptive nature, with an exploratory and qualitative approach, held at the regional hematology center of an inland municipality of Ceará, Brazil, with patients diagnosed and treated for SCA. The data collection was carried out in May 2014, through an interview applied to patients with sickle cell anemia or their respective legal guardians, conducted while they were in the waiting room for medical care in the institution. The following guiding question was asked: “What are the main precautions you take to prevent the complications of sickle cell disease?”. Data were analyzed according to Bardin’s content analysis technique. Results: It was evidenced that patients lack an accurate knowledge about their disease, thus disadvantaging the primary foundation for self-care. The discovery of the disease usually occurs due to the need for clinical interventions in repeated episodes of pain. The painful events represent the main difficulties and causes of hospitalizations with the search for emergency medical services. Conclusion: The educational actions provided by the multidisciplinary health team make it possible for the SCA patient and caregiver to provide better care by means of self-care activities and actions.

This retrospective chart review examined the rate of acute chest syndrome (ACS) in febrile children (aged 3 months to 21 years) with sickle cell disease and used recursive partitioning to determine which clinical factors were predictive of a diagnosis of ACS. Over the course of 2 years, 697 children made 1,837 visits to one of two pediatric emergency departments. ACS was diagnosed in 185 (10%) of the visits.

Sickle cell disease (SCD) is an inherited haemoglobin disorder, associated with recurrent painful episodes, ongoing haemolytic anaemia and progressive multi-organ damage. Until the early 1990s, survival beyond the fourth decade for a patient with SCD was considered unusual and prompted case reports. Nowadays, in countries with developed health care systems, more than 90 percent of newborns with SCD survive into adulthood. Nevertheless, their life expectancy is still shortened by more than two decades compared to the general population. With an increasing life expectancy, SCD has now evolved into a debilitating disorder with substantial morbidity resulting from ongoing sickle cell vasculopathy and multi-organ damage. Limited data on health care issues of older adults with SCD poses multiple challenges to patients, their families and health care providers. In this review, we will address and discuss acute and chronic complications of SCD with a special focus on the older adult.

Our health care system in the United States reflects the inequities that are part of the larger society, which is why our system for financing access to needed and effective health care is so complicated and unfair.

Sickle cell disease (SCD) has a distinct pattern of transfusional iron overload (IO) when compared to transfusion-dependent β-thalassaemia major (TDT). We conducted a single institution prospective study to evaluate plasma biomarkers of iron regulation and inflammation in patients with SCD with IO (SCD IO cases, n = 22) and without IO (SCD non-IO cases, n = 11), and non-SCD controls (n = 13). Hepcidin was found to be inappropriately low, as evidenced by a significantly higher median hepcidin/ferritin ratio in non-SCD controls compared to SCD IO cases (0.3 vs. 0.02, P < 0.0001) and SCD non-IO cases (0.3 vs. 0.02, P < 0.0001), suggesting that certain inhibitory mechanism (s) work to suppress hepcidin in SCD. As opposed to the SCD non-IO state, where hepcidin shows a strong significant positive correlation with ferritin (Spearman ρ = 0.7, P = 0.02), this correlation was lost when IO occurs (Spearman ρ = −0.2, P = 0.4). Although a direct non-linear correlation between erythroferrone (ERFE) and hepcidin did not reach statistical significance both in the IO (Spearman ρ = −0.4, P = 0.08) and non-IO state (Spearman ρ = −0.6, P = 0.07), patients with highest ERFE had low hepcidin levels, suggesting that ERFE contributes to hepcidin regulation in some patients. Our results suggest a multifactorial mechanism of hepcidin regulation in SCD.

Red blood cell (RBC) alloimmunization varies across human populations and ethnic groups. We evaluated the characteristics of RBC alloimmunization and compared the risk of alloimmunization in Korean patients with myelodysplastic syndrome (MDS) and liver cirrhosis (LC), two representative diseases in which chronic transfusion is required. In total, 115 MDS patients and 202 LC patients transfused with RBCs between 2013 and 2015 were retrospectively included. Twenty patients (6.3%) were newly alloimmunized (five MDS patients, 4.3%; 15 LC patients, 7.4%). The median number of RBC units transfused in alloimmunized patients was nine (interquartile range, 4–15 units). As the number of transfused RBC units increased, the cumulative risk of alloimmunization was higher in LC than in MDS patients (P=0.001). The most common alloantibody detected in patients was anti-E (45%), followed by anti-c (17%), anti-e (10%), anti-C (7%), anti-Fyb (7%), and anti-Jka (7%). The present data indicate the need for matching of extended RBC antigens (Rh, Duffy, and Kidd systems) for chronically transfused patients with MDS and LC in Korea.

Apart from hemoglobin-S (HbS), there are other Hb variants (non-S sickling Hb variants) that cause sickle cell disease. However, the profiles of these non-S sickling Hb variants have neither been collated nor harmonized. A literature search revealed 14 non-S sickling Hb variants (HbC-Harlem, HbC-Ziguinchor, HbS-Travis, HbS-Antilles, HbS-Providence, HbS-Oman, HbS-Cameroon, HbS-South End, Hb Jamaica Plain, HbC-Ndjamena, HbS-Clichy, HbS-San Martin, HbS-Wake, and HbS-São Paulo). Generally, the non-S sickling Hb variants are double mutants with the HbS mutation (GAG>GTG: βGlu6Val) and additional β-chain mutations. Consequently, non-S sickling Hb variants give positive solubility and sickling tests, but they differ from HbS with respect to stability, oxygen affinity, and electro-chromatographic characteristics. Similarities and discrepancies between HbS and non-S sickling Hb variants create diagnostic pitfalls that can only be resolved by elaborate electro-chromatographic and/or genetic tests. It is therefore imperative that tropical hematologists should have a thorough understanding of these atypical sickling Hb variants. Collated and harmonized appraisal of the non-S sickling Hb variants have not been previously undertaken. Hence, this paper aims to provide a comprehensive but concise historical, genetic, comparative, diagnostic, and clinical overview of non-S sickling Hb variants. The elaborate techniques often required for precise diagnosis of non-S sickling Hb variants are regrettably not readily available in low resource tropical countries, which paradoxically carry the heaviest burden of sickling disorders. We strongly recommend that tropical countries should upgrade their diagnostic laboratory facilities to avoid misdiagnosis of these atypical Hb mutants.

Red cell transfusion has an important role in the management of sickle cell disease (SCD) in both emergency and elective settings. However, because of insufficient randomised data, it is not always clear when or how to use red cell transfusion. A companion guideline, Guidelines on red cell transfusion in sickle cell disease Part I: principles and laboratory aspects, addresses the general principles of transfusion practice in SCD (Davis et al, 2016, BJH in press). The present guideline examines current available evidence on indications for transfusion in SCD. This may not be appropriate for all clinical scenarios and clinical decisions must be based on individual patient considerations. In both guidelines, the term sickle cell disease refers to all genotypes of the disease, and sickle cell anaemia to the homozygous state (SS).

Acute and chronic pulmonary complications leading to significant morbidity and mortality occur in persons with sickle cell disease (SCD). One of the leading causes of death is acute chest syndrome (ACS),[1][1] diagnosed by a new infiltrate on chest x-ray often triggered by infection.[2][2] The

Objective: To describe and quantify the main changes seen on computed tomography of the chest in mildly symptomatic adult patients with sickle cell disease, as well as to evaluate the radiologist accuracy in determining the type of hemoglobinopathy. Materials and Methods: A prospective study involving 44 adult patients with sickle cell disease who underwent inspiration and expiration computed tomography of the chest. The frequency of tomography findings and the extent of involvement are reported. We also calculated radiologist accuracy in determining the type of hemoglobinopathy by analyzing the pulmonary alterations and morphology of the spleen. Results: The changes found on computed tomography scans, in descending order of frequency, were as follows: fibrotic opacities (81.8%); mosaic attenuation (56.8%); architectural distortion (31.8%); cardiomegaly (25.0%); lobar volume reduction (18.2%); and increased caliber of peripheral pulmonary arteries (9.1%). For most of the findings, the involvement was considered mild, five or fewer lung segments being affected. The accuracy in determining the type of hemoglobinopathy (HbSS group versus not HbSS group) was 72.7%. Conclusion: In adult patients with sickle cell disease, the main tomography findings reflect fibrotic changes. In addition, computed tomography can be helpful in differentiating among hemoglobinopathies. Resumo Objetivo: Descrever e quantificar as principais alterações na tomografia computadorizada do tórax em pacientes adultos oligossintomáticos com doença falciforme e, secundariamente, avaliar o índice de acerto do radiologista quanto ao tipo de hemoglobinopatia. Materiais e Métodos: Estudo prospectivo em que 44 pacientes adultos com doença falciforme foram submetidos a tomografia computadorizada do tórax tanto em inspiração como em expiração. Foram descritos a frequência dos achados tomográficos e os graus de acometimento. Por meio da análise das alterações pulmonares e do padrão morfológico do baço, foi calculado o índice de acerto do radiologista quanto ao tipo de hemoglobinopatia. Resultados: As alterações encontradas nos exames de tomografia computadorizada, em ordem decrescente de frequência, foram: opacidades reticulares (81,8%), padrão de atenuação em mosaico (56,8%), distorção arquitetural (31,8%), cardiomegalia (25%), redução volumétrica lobar (18,2%) e aumento do calibre de ramos periféricos das artérias pulmonares (9,1%). Na maioria dos achados o grau de acometimento foi considerado leve, com até cinco segmentos pulmonares acometidos. O índice de acerto quanto ao tipo de hemoglobinopatia (grupo HbSS versus grupo não HbSS) foi 72,7%. Conclusão: Em pacientes adultos com doença falciforme os principais achados tomográficos refletem alterações fibróticas. Além do mais, a tomografia computadorizada pode ser útil na diferenciação do tipo de hemoglobinopatia.

Objective To determine (i) if electrospray mass spectrometry–mass spectrometry with the SpOtOn Diagnostics Ltd reagent kit for sickle cell screening could be integrated into the English newborn screening programme, under routine screening conditions, and provide mass spectrometry–mass spectrometry results which match existing methods, and (ii) if common action values could be set for all manufacturers in the study, for all assessed haemoglobins, to indicate which samples require further investigation. Methods Anonymised residual blood spots were analysed using the SpOtOn reagent kit as per manufacturer’s instructions, in parallel with existing techniques at four laboratories. Mass spectrometry–mass spectrometry instrumentation at Laboratories A and B was AB Sciex (Warrington, UK) AP4000, and at Laboratories C and D, Waters Micromass (Manchester, UK), Xevo TQMS and Premier, respectively. Results There were 23,898 results accepted from the four laboratories. Excellent specificity at 100% sensitivity was observed for haemoglobin S, haemoglobin C, haemoglobin E and haemoglobin OArab. A common action value was not possible for Hb C, but action values were set by manufacturer. The two haemoglobin DPunjab cases at Laboratory D were not detected using the common action value. Conversely, false-positive results with haemoglobin DPunjab were a problem at the remaining three laboratories. Conclusions This multicentre study demonstrates that it is possible to implement mass spectrometry–mass spectrometry into an established screening programme while maintaining consistency with existing methods for haemoglobinopathy screening. However, one of the instruments investigated cannot be recommended for use with this application.

Adherence to hydroxyurea (HU) is a significant modifying factor in sickle cell vaso-occlusive pain. We conducted a study using an electronic medication container-monitor-reminder device (GlowCap™) to track adherence and determine whether use of this device affected rates of HU adherence. Subjects were regular attendees to our clinic. They were given a 37-item questionnaire and were asked to use a GlowCap containing HU. When the device cap is opened, it makes a remote "medication taken" record. The device also provides usage reminder in the form of lights and alarm sounds if the cap opening is delayed. Nineteen subjects participated in the survey, and 17 in the intervention phase. Of the 17, 12 had reliable adherence data. Seventeen caregivers of patients and two patients completed the survey. Two most common barriers to adherence identified were lack of reminders and absence of medicine home delivery. The intervention component of this study, which used both the electronic (GlowCap) method and medication possession ratio showed that the median adherence rate for the 12 patients evaluated was 85 %. The GlowCap device accurately kept a record of adherence rates. This device may be an effective tool for increasing HU medication adherence.

SUMMARY Objectives Comparison of the alloimmunisation rates of patients with sickle cell disease in the Unites States versus other countries. Background Sickle cell disease (SCD) patients treated with chronic transfusion therapy are at a high risk of red blood cell (RBC) alloimmunisation. Materials and Methods We reviewed published literature describing alloimmunisation rates of SCD patients. Average alloimmunisation rates and number of alloantibodies per transfused patient in the United States and other countries were evaluated. Results Twenty-four studies on alloimmunisation of SCD patients were found, 15 studies with 3,708 patients in the US and 10 studies with 2203 patients from other regions, including South America, the Caribbean, Middle East, Africa and Europe. The United States has a higher alloimmunisation rate (22·33 ± 0·13% versus 16·25 ± 0·35%, p

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.

Painful vaso-occlusive crisis (VOC) is the clinical hallmark of sickle cell disease (SCD). Microcirculatory hemodynamic changes following painful VOC may be indicative of future development of VOC events in subjects with SCD. The purpose of the present study was to determine alterations in conjunctival microvascular hemodynamics during non-crisis state in SCD subjects with a history of VOC. Conjunctival microcirculation imaging was performed to measure conjunctival diameter (D) and axial blood velocity (V) in 10 control and 30 SCD subjects. SCD subjects were categorized into two groups based on their history of VOC within a 2-year period before imaging (with or without VOC-H) and also based on whether there was progression in the rate of VOCs during a 2-year period following imaging as compared to before imaging (with or without VOC-P). Conjunctival V was significantly higher in SCD subjects with VOC-H than in both control subjects and SCD subjects without VOC-H (P≤0.03). Conjunctival V was also significantly higher in SCD subjects with VOC-P compared with control subjects and SCD subjects without VOC-P (P≤0.03). Assessment of the conjunctival microcirculation may be useful for understanding hemodynamic changes that lead to VOC events in SCD subjects.

Background Patient diaries and pain scales can capture the course and complications of pain managed at home in children. The Faces Pain Scale-Revised (FPS-R) is a validated scale showing reliability in children, but it has not been validated in children with sickle cell disease (SCD). Objective The purpose of this study was to evaluate comprehension and usability of an electronic modified version of the FPS-R among pediatric patients with SCD. Methods This was a cross-sectional, qualitative study involving in-person interviews with children/adolescents from the USA and their parents/legal guardians. Interviews involved cognitive debriefing and usability testing of the FPS-R. Results In total, 22 children with SCD aged 4–17 years participated. Children aged 4–6 were generally unable to demonstrate clear understanding of the FPS-R and its response scale. Overall, children aged ≥7 years understood the instrument and could complete it on the electronic device, although children aged 7–8 often needed assistance from the parent. Children aged 9–17 years were able to read and complete the instrument independently. Most participants considered the electronic device easy to use. Conclusions The FPS-R was shown to be a comprehensible and usable pain measure for children aged 7–17 with SCD and to be beneficial for future clinical studies.

Aufgrund von Migration und Flucht sind Hamoglobinopathien und der Glukose-6-Phosphat-Dehydrogenase-Mangel in Deutschland keine seltenen Erkrankungen mehr. Durch die aktuellen Fluchtlingsbewegungen werden diese genetisch determinierten Erkrankungen an Bedeutung gewinnen. Auf Basis einer Literaturrecherche wurden die Pravalenzen von genetisch determinierten Anamien in den ursprunglichen Endemiegebieten zusammengestellt. Die gewonnenen Daten wurden mit Statistiken zur Bevolkerungszusammensetzung in Bezug auf Migration, Auslander und Asylsuchende in Deutschland verglichen. Die Endemiegebiete weisen fur den Glukose-6-Phosphat-Dehydrogenase-Mangel und fur Hamoglobinopathien teilweise Pravalenzen von 40 % und mehr auf. Der Anteil der Personen aus den Endemiegebieten nimmt rapide zu. Durch die hohe Zahl an Fluchtlingen aus asiatischen und afrikanischen Gebieten wird die Bedeutung der genetisch determinierten Erythrozytendefekte in der Differenzialdiagnose der Anamien zunehmen. Die Vermittlung von Kenntnissen uber Gefahren, Diagnostik und Therapie muss in der medizinischen Aus- und Fortbildung besser organisiert werden.

This paper approaches the lived experiences of patients with a genetically inherited chronic disease, sickle cell disease (SCD), through the lens of (in)visibility. SCD has been referred to as an "invisible" disease for a variety of interrelated reasons, including the difficulty of objectively measuring its characteristic symptoms, the lack of popular or specialist attention, and its characterization as a "black" disease. By mobilizing "invisibility" as a way of probing the day-to-day reinforcements of marginality, this article delves into how structural forces are experienced, interpreted, and negotiated by individual actors. To this end, we present ethnographic data collected from November 2009 until November 2013 with SCD patients and healthcare workers in Chicago. These data emphasize that rendering (in)visible is not a totalizing act, but rather meaningfully breaks the body into differentially visible and ideology-laden parts. More broadly, this indicates the need to rigorously question sources and effects of authority in biomedicine.

Managing sickle cell carrier results generated through newborn screening in Ontario: a precedent-setting policy story

Objective: Hospital admissions are significant events in the care of individuals with sickle cell disease (SCD) due to associated costs and potential for quality of life compromise. Methods: This cross-sectional cohort study evaluated risk factors for admissions and readmissions between October 2014 and March 2016 in adults with SCD (n = 201) and caregivers of children with SCD (n = 330) at six centres across the U.S. Survey items assessed social determinants of health (e.g. educational attainment, difficulty paying bills), depressive symptoms, social support, health literacy, spirituality, missed clinic appointments, and outcomes hospital admissions and 30-day readmissions in the previous year. Results: A majority of adults (64%) and almost half of children (reported by caregivers: 43%) were admitted, and fewer readmitted (adults: 28%; children: 9%). The most common reason for hospitalization was uncontrolled pain (admission: adults: 84%, children: 69%; readmissions: adults: 83%, children: 69%). Children were less likely to have admissions/readmissions than adults (Admissions: OR: 0.35, 95% CI: [0.23,0.52]); Readmissions: 0.23 [0.13,0.41]). For all participants, missing appointments were associated with admissions (1.66 [1.07, 2.58]) and readmissions (2.68 [1.28, 6.29]), as were depressive symptoms (admissions: 1.36 [1.16,1.59]; readmissions: 1.24 [1.04, 1.49]). In adults, difficulty paying bills was associated with more admissions, (3.11 [1.47,6.62]) readmissions (3.7 [1.76,7.79]), and higher spirituality was associated with fewer readmissions (0.39 [0.18,0.81]). Discussion: Missing appointments was significantly associated with admissions and readmissions. Findings confirm that age, mental health, financial insecurity, spirituality, and clinic attendance are all modifiable factors that are associated with admissions and readmissions; addressing them could reduce hospitalizations.

Sickle cell disease (SCD) is associated with intravascular hemolysis and oxidative inhibition of nitric oxide (NO) signaling. BAY 54-6544 is a small-molecule activator of oxidized soluble guanylate cyclase (sGC), which, unlike endogenous NO and the sGC stimulator, BAY 41-8543, preferentially binds and activates heme-free, NO-insensitive sGC to restore enzymatic cGMP production. We tested orally delivered sGC activator, BAY 54-6544 (17 mg/kg/d), sGC stimulator, BAY 41-8543, sildenafil, and placebo for 4-12 weeks in the Berkeley transgenic mouse model of SCD (BERK-SCD) and their hemizygous (Hemi) littermate controls (BERK-Hemi). Right ventricular (RV) maximum systolic pressure (RVmaxSP) was measured using micro right-heart catheterization. RV hypertrophy (RVH) was determined using Fulton's index and RV corrected weight (ratio of RV to tibia). Pulmonary artery vasoreactivity was tested for endothelium-dependent and -independent vessel relaxation. Right-heart catheterization revealed higher RVmaxSP and RVH in BERK-SCD versus BERK-Hemi, which worsened with age. Treatment with the sGC activator more effectively lowered RVmaxSP and RVH, with 90-day treatment delivering superior results, when compared with other treatments and placebo groups. In myography experiments, acetylcholine-induced (endothelium-dependent) and sodium-nitroprusside-induced (endothelium-independent NO donor) relaxation of the pulmonary artery harvested from placebo-treated BERK-SCD was impaired relative to BERK-Hemi but improved after therapy with sGC activator. By contrast, no significant effect for sGC stimulator or sildenafil was observed in BERK-SCD. These findings suggest that sGC is oxidized in the pulmonary arteries of transgenic SCD mice, leading to blunted responses to NO, and that the sGC activator, BAY 54-6544, may represent a novel therapy for SCD-associated pulmonary arterial hypertension and cardiac remodeling.

The St. Jude Children’s Research Hospital (St. Jude) comprehensive sickle cell center serves a 150 mile catchment radius around Memphis, TN, USA. Full travel expenses are provided for routine and acute care visits for sickle cell disease patients living ≥35 miles from St. Jude. We compared hospitalization rates to national estimates and assessed if driving distance was a barrier to sickle cell healthcare despite the travel reimbursement policy. We evaluated the associations between hospitalizations and routine clinic visits and distance from St. Jude using negative binomial models and we conducted bias analyses by Monte Carlo simulation. We followed 545 patients (2550 patient-years) aged ≤18 years with sickle cell disease (Hb SS only) from 2007 to 2012. The hospitalization rate per patient-year was 0.65 [95% CI (confidence interval): 0.62, 0.68), significantly lower than the national rate of 1.16 (95% CI: 1.14, 1.18). Children living 35 miles) was associated with decreased hospitalization rates, despite the travel allowances that are provided for those who live ≥35 miles from the hospital.

Introduction: Fetal hemoglobin is an important factor in modulating the severity of sickle cell anemia. Its level in peripheral blood underlies strong genetic determination. Associated loci with increased levels of fetal hemoglobin display population-specific allele frequencies. Objective: We investigated the presence and effect of known common genetic variants promoting fetal hemoglobin persistence (rs11886868, rs9399137, rs4895441, and rs7482144) in 60 Colombian patients with sickle cell anemia. Materials and methods: Four single nucleotide polymorphisms (SNP) were genotyped by restriction fragment length polymorphisms (RFLP) and the use of the TaqMan procedure. Fetal hemoglobin (HbF) from these patients was quantified using the oxyhemoglobin alkaline denaturation technique. Genotype frequencies were compared with frequencies reported in global reference populations. Results: We detected genetic variants in the four SNPs, reported to be associated with higher HbF levels for all four SNPs in the Colombian patients. Genetic association between SNPs and HbF levels did not reach statistical significance. The frequency of these variants reflected the specific ethnic make-up of our patient population: A high prevalence of rs7482144-'A' reflects the West-African origin of the sickle cell mutation, while high frequencies of rs4895441-'G' and rs11886868-'C' point to a significant influence of an Amerindian ethnic background in the Colombian sickle cell disease population. Conclusion: These results showed that in the sickle cell disease population in Colombia there is not a unique genetic background, but two (African and Amerindian). This unique genetic situation will provide opportunities for a further study of these loci, such as fine-mapping and molecular-biological investigation. Colombian patients are expected to yield a distinctive insight into the effect of modifier loci in sickle cell disease. Introducción. La hemoglobina fetal es un importante factor modulador de la gravedad de la anemia falciforme, cuya expresión está muy condicionada por el factor genético. Los loci asociados con el incremento de la hemoglobina fetal pueden presentar frecuencias alélicas específicas para cada población. Objetivo. Investigar la presencia y el efecto de las variantes genéticas rs11886868, rs9399137, rs4895441 y rs7482144 asociadas con la persistencia de hemoglobina fetal, en 60 pacientes colombianos con anemia falciforme. Materiales y métodos. Se hizo la genotipificación de los polimorfismos de nucleótido simple ( Single Nucleotide Polymorphisms, SNP) mediante la técnica de polimorfismos de longitud de fragmentos de restricción ( Restriction Fragment Length Polymorphisms, RFLP) y el procedimiento TaqMan. La hemoglobina fetal (HbF) se cuantificó utilizando la técnica de desnaturalización alcalina de la oxihemoglobina. Las frecuencias genotípicas se compararon con las reportadas en poblaciones de referencia global. Resultados. Se observaron variantes genéticas ya reportadas para aumento de HbF en los cuatro SNP. La asociación genética entre los SNP y el incremento de la HbF no alcanzó significancia estadística. La frecuencia de estos alelos reflejó la siguiente composición específica en esta muestra de pacientes colombianos: una gran prevalencia de rs7482144-'A', lo que indica que el origen de la mutación para la anemia falciforme es África occidental, y una gran frecuencia de rs4895441-'G' y rs11886868-'C', lo que denota la influencia significativa del origen genético amerindio. Conclusión. Los resultados evidenciaron que la población con anemia falciforme de Colombia no tiene un único origen genético, sino que existen dos (africano y amerindio). Esta situación genética única ofrece la oportunidad de llevar a cabo un estudio más amplio de estos loci a nivel molecular. Se espera que el estudio de pacientes colombianos permita una visión diferente del efecto de los loci modificadores en esta enfermedad.

Background Sickle cell anemia (SCA) is an inherited hematological disorder that causes a large but neglected global health burden, particularly in Africa. Hydroxyurea represents the only available disease‐modifying therapy for SCA, and has proven safety and efficacy in high‐resource countries. In sub‐Saharan Africa, there is minimal use of hydroxyurea, due to lack of data, absence of evidence‐based guidelines, and inexperience among healthcare providers. Procedure A partnership was established between investigators in North America and sub‐Saharan Africa, to develop a prospective multicenter research protocol designed to provide data on the safety, feasibility, and benefits of hydroxyurea for children with SCA. Results The Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) trial is a prospective, phase I/II open‐label dose escalation study of hydroxyurea that will treat a total of 600 children age 1–10 years with SCA: 150 at each of four different clinical sites within sub‐Saharan Africa (Angola, Democratic Republic of Congo, Kenya, and Uganda). The primary study endpoint will be severe hematological toxicities that occur during the fixed‐dose treatment phase. REACH has an adaptive statistical design that allows for careful assessment of toxicities to accurately identify a safe hydroxyurea dose. Conclusions REACH will provide data that address critical gaps in knowledge for the treatment of SCA in sub‐Saharan Africa. By developing local expertise with the use of hydroxyurea and helping to establish treatment guidelines, the REACH trial results will have the potential to transform care for children with SCA in Africa. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.

Sickle cell disease has become the most common genetic condition in some European countries (Roberts & De Montalembert 2007). The disease is characterised by the painful sickle cell crisis often experienced by sufferers. This article sets out to examine the pathophysiology of this disease, alongside the factors that perioperative practitioners need to be aware of in order to reduce the risk of triggering a sickle cell crisis.

Long-term follow-up of newborn screening for conditions such as sickle cell disease can be conducted using linkages to population-based data. We sought to estimate childhood sickle cell disease mortality and risk factors among a statewide birth cohort with sickle cell disease identified through newborn screening.Children with sickle cell disease identified by newborn screening and born to New York residents in 2000-2008 were matched to birth and death certificates. Mortality rates were calculated (using numbers of deaths and observed person-years at risk) and compared with mortality rates for all New York children by maternal race/ethnicity. Stratified analyses were conducted to examine associations between selected factors and mortality.Among 1,911 infants with sickle cell disease matched to birth certificates, 21 deaths were identified. All-cause mortality following diagnosis was 3.8 per 1,000 person-years in the first 2 years of life and 1.0 per 1,000 person-years at ages 2-9 years. The mortality rate was significantly lower among children of foreign-born mothers and was significantly higher among preterm infants with low birth weight. The mortality rates were not significantly higher for infants after 28 days with sickle cell disease than for all New York births, but they were 2.7-8.4 times higher for children 1 through 9 years old with homozygous sickle cell disease than for those of all non-Hispanic black or Hispanic children born to New York residents.Estimated mortality risk in children with homozygous sickle cell disease remains elevated even after adjustment for maternal race/ethnicity. These results provide evidence regarding the current burden of child mortality among children with sickle cell disease despite newborn screening.Genet Med 17 6, 452-459.

Vaso-occlusive crisis is the primary reason for emergency medical care sought by Sickle Cell Disease (SCD) patients.[1][1] In vivo imaging in transgenic SCD mice has identified molecular events that may promote vaso-occlusion.[2][2]–[4][3] However, the relevance of these mechanisms is not

I am enormously grateful to The American Society of Human Genetics (ASHG) for selecting me to join the distinguished roster of recipients of the William Allan Award. I especially thank Haig Kazazian, a former recipient and a wonderful collaborator in the early days of my independent career, for the nomination and the gracious introduction today. I am not a conventional awardee for this honor, given that I have never held an appointment in a genetics department or division. Instead, my research career developed in a division of hematology.

The lack of an ongoing surveillance system for hemoglobinopathies in the United States impedes the ability of public health organizations to identify individuals with these conditions, monitor their health-care utilization and clinical outcomes, and understand the effect these conditions have on the health-care system. This article describes the results of a pilot program that supported the development of the infrastructure and data collection methods for a state-based surveillance system for selected hemoglobinopathies. The system was designed to identify and gather information on all people living with a hemoglobinopathy diagnosis (sickle cell diseases or thalassemias) in the participating states during 2004–2008. Novel, three-level case definitions were developed, and multiple data sets were used to collect information. In total, 31,144 individuals who had a hemoglobinopathy diagnosis during the study period were identified in California; 39,633 in Florida; 20,815 in Georgia; 12,680 in Michigan; 34,853 in New York, and 8,696 in North Carolina. This approach provides a possible model for the development of state-based hemoglobinopathy surveillance systems. Genet Med 17 2, 125–130.

A novel concept of Brillouin imaging and sensing via time-resolved optical (BISTRO) measurements is introduced for flow cytometry applications. The system affords robust, maintenance-free and high-speed elasticity-sensitive measurements.

Background The purpose of this study was to compare longitudinal trajectories of maximal aerobic capacity in children with sickle cell anemia (SCA) and matched healthy controls, and explore whether these trajectories were associated with selected physiologic variables. Procedure Children with SCA (n = 33) and healthy controls (n = 30) matched at baseline for race, sex, Tanner stage, height, and weight completed three consecutive annual fitness assessments (VO2peak). Data were compared between the groups at each time point and within groups over time. Change in VO2peak between the two groups over time was assessed using a linear mixed model with age, sex, fat-free mass (FFM), Tanner stage, and hemoglobin (Hgb) concentration as covariates. Results At baseline, children with SCA had significantly lower Hgb concentration (8.9 vs. 13.7 g/dL, P