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Sickle cell disease (SCD) is a single gene disorder causing a debilitating systemic syndrome characterised by chronic anaemia, acute painful episodes, organ infarction and chronic organ damage and by a significant reduction in life expectancy. The origin of SCD lies in the malarial regions of the tropics where carriers are protected against death from malaria and hence enjoy an evolutionary advantage. More recently, population migration has meant that SCD now has a worldwide distribution and that a substantial number of children are born with the condition in higher-income areas, including large parts of Europe and North and South America. Newborn screening, systematic clinical follow-up and prevention of sepsis and organ damage have led to an increased life expectancy among people with SCD in many such countries; however, in resource-limited settings where the majority continue to be born, most affected children continue to die in early childhood, usually undiagnosed, due to the lack of effective programmes for its early detection and treatment. As new therapies emerge, potentially leading to disease amelioration or cure, it is of paramount importance that the significant burden of SCD in resource-poor countries is properly recognised.

ObjectiveThe purpose of this retrospective cross-sectional study was to investigate whether changes in white matter integrity are related to slower processing speed in sickle cell anemia.MethodsThirty-seven patients with silent cerebral infarction, 46 patients with normal MRI, and 32 sibling controls (age range 8–37 years) underwent cognitive assessment using the Wechsler scales and 3-tesla MRI. Tract-based spatial statistics analyses of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters were performed.ResultsProcessing speed index (PSI) was lower in patients than controls by 9.34 points (95% confidence interval: 4.635–14.855, p = 0.0003). Full Scale IQ was lower by 4.14 scaled points (95% confidence interval: −1.066 to 9.551, p = 0.1), but this difference was abolished when PSI was included as a covariate (p = 0.18). There were no differences in cognition between patients with and without silent cerebral infarction, and both groups had lower PSI than controls (both p < 0.001). In patients, arterial oxygen content, socioeconomic status, age, and male sex were identified as predictors of PSI, and correlations were found between PSI and DTI scalars (fractional anisotropy r = 0.614, p < 0.00001; r = −0.457, p < 0.00001; mean diffusivity r = −0.341, p = 0.0016; radial diffusivity r = −0.457, p < 0.00001) and NODDI parameters (intracellular volume fraction r = 0.364, p = 0.0007) in widespread regions.ConclusionOur results extend previous reports of impairment that is independent of presence of infarction and may worsen with age. We identify processing speed as a vulnerable domain, with deficits potentially mediating difficulties across other domains, and provide evidence that reduced processing speed is related to the integrity of normal-appearing white matter using microstructure parameters from DTI and NODDI.

SummaryAlthough neonatal thrombocytopenia (platelet count < 150 · 10 9 /l) is a common finding in hospital practice, a careful clinical history and examination of the blood film is often sufficient to establish the diagnosis and guide management without the need for further investigations. In preterm neonates, early-onset thrombocytopenia (<72 h) is usually secondary to antenatal causes, has a characteristic pattern and resolves without complications or the need for treatment. By contrast, late-onset thrombocytopenia in preterm neonates (>72 h) is nearly always due to post-natally acquired bacterial infection and/or necrotizing enterocolitis, which rapidly leads to severe thrombocytopenia (platelet count < 50 · 10 9 /l).Thrombocytopenia is much less common in term neonates and the most important cause is neonatal alloimmune thrombocytopenia (NAIT), which confers a high risk of perinatal intracranial haemorrhage and long-term neurological disability. Prompt diagnosis and transfusion of human platelet antigen-compatible platelets is key to the successful management of NAIT. Recent studies suggest that more than half of neonates with severe thrombocytopenia receive platelet transfusion(s) based on consensus national or local guidelines despite little evidence of benefit. The most pressing problem in management of neonatal thrombocytopenia is identification of safe, effective platelet transfusion therapy and controlled trials are urgently needed.

Key Points Hermansky-Pudlak syndrome type 2 confers a moderate risk for hemophagocytic lymphohistiocytosis.

Faced with the rapidly evolving COVID-19 pandemic, in March 2020 the UK Government advocated strict self-isolation ('shielding') to protect extremely vulnerable patient groups deemed at high risk of severe SARS-CoV-2 infection. 1 These included children and adults with sickle cell anemia (HbSS). On the advice of the National Hemoglobinopathy Panel (NHP), a multidisciplinary expert advisory group, shielding guidance was extended to all sickle cell disease (SCD) sub-types. Patients with transfusion dependent (TDT) and non-transfusion dependent thalassemia (NTDT), Diamond-Blackfan anemia (DBA) and other rare inherited anemias were also advised to shield if considered at high risk based on agreed clinical criteria. These included severe iron overload, splenectomy, diabetes and cardiac disease. 2 Data provided by two participating centers with the largest thalassemia cohorts indicate up to 30% of patients meet these criteria. In order to evaluate the impact of these measures and inform guidance on the clinical management of COVID-19 and public health policy, a real-time survey of confirmed and suspected cases of COVID-19 in hemoglobinopathy and rare inherited anemia patients was initiated on behalf of the NHP and National Health Service (NHS) England Clinical Reference Group for Hemoglobinopathies. Data were submitted weekly by the 14 Hemoglobinopathy Coordinating Centers (HCC) in England, providing national coverage. HCC were encouraged to follow World Health Organization (WHO) case definitions which include both confirmed and clinically suspected COVID-19. 3 Anonymised data were collected using a standardised report template (see the Online Supplementary Data) and presented weekly to the NHP. Between April 8 and May 6, 2020, a total of 195 confirmed or suspected COVID-19 cases (male: 87; female: 108) were reported. The timeline of case accrual is shown in Figure 1A. The median age was 33 years (range: 6 weeks to 92 years). The distribution according to age and sex is shown in Figure 1B. PCR for SARS-CoV-2 RNA was positive in 99 of 157 (63%) cases tested (Figure 2A). Laboratory confirmation was not available for 34 (17.4%) cases, 31 of which were managed in the community for suspected COVID-19 before widespread testing became available. SCD accounted for 166 (85.1%) of cases reported, with 129 (77.7%) severe (HbSS or HbSβ 0-thalassemia) and 37 (22.3%) mild (HbSC, HbSβ +-thalassemia or HbSE) genotypes (Figures 2A-B). There were 149 adults and 17 children (defined as ≤18 years). Ninety-five (57%) were female. One hundred and twenty-eight (77.1%) SCD patients were admitted to hospital of whom 15 (11.7%), all adults, required non-invasive and/or mechanical ventilation (Figure 2B). The proportion of patients who required critical care was higher in mild genotypes, 8 of 29 (27.6%), than severe genotypes, 7 of 99 (7.1%) (Figure 2B). Sixty of 154 (39%) patients for whom data were available received transfusion (red cell exchange 46 [29%]; simple [top-up] transfusion 15 [10%]) during the COVID-19 episode. The proportion of tr...

Summary With the developing COVID‐19 pandemic, patients with inherited anaemias require specific advice regarding isolation and changes to usual treatment schedules. The National Haemoglobinopathy Panel (NHP) has issued guidance on the care of patients with sickle cell disease, thalassaemia, Diamond Blackfan anaemia (DBA), congenital dyserythropoietic anaemia (CDA), sideroblastic anaemia, pyruvate kinase deficiency and other red cell enzyme and membrane disorders. Cascading of accurate information for clinicians and patients is paramount to preventing adverse outcomes, such as patients who are at increased risk of fulminant bacterial infection due to their condition or its treatment erroneously self‐isolating if their fever is mistakenly attributed to a viral cause, delaying potentially life‐saving antibiotic therapy. Outpatient visits should be minimised for most patients, however some, such as first transcranial dopplers for children with sickle cell anaemia should not be delayed as known risk of stroke will outweigh the unknown risk from COVID‐19 infection. Blood transfusion programmes should be continued, but specific changes to usual clinical pathways can be instituted to reduce risk of patient exposure to COVID‐19, as well as contingency planning for possible reductions in blood available for transfusions. Bone marrow transplants for these disorders should be postponed until further notice. With the current lack of evidence on the risk and complications of COVID‐19 infection in these patients, national data collection is ongoing to record outcomes and eventually to identify predictors of disease severity, particularly important if further waves of infection travel through the population.

BackgroundYoung people’s experiences of healthcare as they move into adult services can have a major impact on their health, and the transition period for young people with sickle cell disease (SCD) needs improvement. In this study, we explore how young people with SCD experience healthcare during this period of transition.MethodsWe conducted a co-produced longitudinal qualitative study, including 80 interviews in 2016–2017 with young people with SCD aged 13–21 (mean age 16.6) across two cities in England. We recruited 48 participants (30 female, 18 male): 27 interviews were one-off, and 53 were repeated 2–3 times over approximately 18 months. We used an inductive analytical approach, combining elements of Grounded Theory and thematic analysis.ResultsParticipants reported significant problems with the care they received in A&E during painful episodes, and in hospital wards as inpatients during unplanned healthcare. They experienced delays in being given pain relief and their basic care needs were not always met. Participants said that non-specialist healthcare staff did not seem to know enough about SCD and when they tried to work with staff to improve care, staff often seemed not prepared to listen to them or act on what they said. Participants said they felt out of place in adult wards and uncomfortable with the differences in adult compared with paediatric wards. Because of their experiences, they tried to avoid being admitted to hospital, attempting to manage their painful episodes at home and accessing unplanned hospital care only as a last resort. By contrast, they did not report having problems within SCD specialist services during planned, routine care.ConclusionsOur study underscores the need for improvements to make services youth-friendly and youth-responsive, including training staff in SCD-specific care, compassionate care and communication skills that will help them elicit and act on young people’s voices to ensure they are involved in shaping their own healthcare. If young people are prevented from using transition skills (self-management, self-advocacy), or treated by staff who they worry do not have enough medical competency in their condition, they may well lose their trust in services, potentially compromising their own health.