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Activation of soluble guanylate cyclase (sGC) has been reported to up-regulate γ-globin gene transcription in erythroid cell lines and primary erythroblasts. sGC is activated by nitric oxide (NO), subsequently catalysing the conversion of guanosine triphosphate to cyclic guanosine monophosphate (cGMP), which mediates various physiological responses. To study the importance of this mechanism in the erythroid cells of sickle cell patients, cGMP levels were measured in the red blood cells (RBC) of normal individuals, steady-state sickle cell patients (SS) and SS patients on hydroxyurea (HU) therapy (SS + HU). cGMP levels were found to be significantly higher in RBC of SS patients (SS RBC) than in RBC of normal individuals, and were further increased in RBC of SS + HU patients. cGMP levels correlated with fetal haemoglobin (HbF) levels in SS/SS + HU patients, but not with reticulocyte count. Furthermore, NO-stimulated sGC activity, following incubation of cells with a NO donor, was significantly greater in SS RBC than in normal RBC. These results demonstrate, for the first time, an increased metabolism of NO mediated by sGC in the SS RBC, which is further increased by hydroxyurea. Augmentation of cGMP levels by NO in erythroid cells may constitute a mechanism for induction of HbF and other erythrocyte functions and represent a possible therapeutic target for treatment of sickle cell disease. [ABSTRACT FROM AUTHOR]

The article lists articles in forthcoming issues on topics including sickle cell disease, acute lymphoblastic leukaemia, and autoimmune diseases.

The article lists several papers that are to be published in various issues of the "British Journal of Haematology." Some of the papers are, "An Unusual Case of Venous Thromboembolism," by J. Motwani, P. E. Rose and W. Shatwell; "Expression of Functional Interleukin-21 Receptor on Adult T-cell Leukaemia Cells," by M. Ueda, K. Imada, A. Imura, H. Koga, M. Hishizawa and T. Uchiyama; "Advanced Glycation End-Products in Sickle Cell Anaemia," by S. S. Somjee, R. P. Warner, J.L. Thomson, Ory-Ascani and J.M. Hempe; "Impact of Human Herpesvirus-6 After Haematopoietic Stem Cell Transplantation," by M. Hentrich, D. Oruzio, G. lager, M. Schiemmer, M. Schleuning, X. Schiel, W. Hiddemann and H.-J. Kolb.

Summary: For this paper, cases reported formally and anecdotally to the authors in their screening and diagnostic roles have been selected to demonstrate areas where errors have occurred, and caution should be exercised. The cases demonstrate that it is vital that the performance and limitations of the techniques used, along with the phenotypic presentation of cases where haemoglobin variants and/or thalassaemias are coinherited are understood by those performing result interpretation. Those who deliver the service as well as those who receive reports and give results and counselling should be aware of the complexity of the topic. [ABSTRACT FROM AUTHOR]

Lists the papers to be published in the forthcoming issues of the periodical "British Journal of Haematology". "Cerebral and pulmonary nocardia in a bone marrow transplant patient," by A. D. Laurence and K. S. Peggs; "Heparin-induced skin necrosis," by R. Patel, Z. Lim, S. Dawe, J. Salisbury and R. Arya; "Psychological complications in sickle cell disease," by K. A. Anie.

Lists several papers to be published in the forthcoming issues of the "British Journal of Haematology." "Loss of Skin Pigment Due to Imatinib Therapy," by S. McPartlin and M. Leach; "Predicting Clinical Severity in Sickle Cell Anemia," by M. H. Steinberg; "Bone Involvement in Sickle Cell Disease," by A. Almeida and I. Roberts; Others.

A list of forthcoming articles related to hematology is presented. The articles include "Myocardial Infarction Following Sickle Cell Chest Syndrome," by M. A. Tanner, M. A. Westwood and D. J. Pennell, "A Tribute to Sidney Farber: The Father of Modern Chemotherapy," by D. R. Miller, and "Serum Levels of Angiogenic Factors Indicate a Pro-angiogenic State in Adult with Sickle Cell Disease," by A. J. Duits, T. Rodriguez and J.-J. B. Schnog.

Introduces the articles to be published in the forthcoming issues of the "British Journal of Haematology." "Renal Medullary Carcinoma, a Rare Cause of Haematuria in Sickle Cell Trait," by K. Patel, N. Livni and D. Macdonald; "Managing the Risk of Transmission of Variant Creutzfeldt-Jakob Disease by Blood Products," by C. A. Ludlam and M. L. Turner; "Multicolour Banding Provides a Detailed Characterisation of Structural Abnormalities of Chromosome 1 in Burkitt's lymphoma," by T. Zivkovic, I. Chudoba, C. Bokemeyer and J. Dierlamm.

Pre-eclampsia affects 4-5% of pregnancies worldwide and leads to increased maternal and fetal morbidity and mortality.2 Although the exact mechanisms for developing pre-eclampsia are unclear, placental ischaemia is central in its pathogenesis. Furthermore, those patients with SCD who developed pre-eclampsia had a higher proportion with >=1 VOC/year during their pregnancy compared those that did not have pre-eclampsia (78% vs. 48%). In their paper Boudhabhay I et al i . investigate risk factors and consequences of pre-eclampsia on pregnancy outcomes and kidney function in patients with sickle cell disease (SCD).1 They report that pre-eclampsia: (i) was independently associated with higher body mass index, increased haemolysis and >=1 vaso-occlusive crisis (VOC) requiring hospitalisation; (ii) led to poor maternal and neonatal outcomes and (iii) predicted a more rapid decline in kidney function and greater risk of developing chronic kidney disease (CKD) on longitudinal follow-up. [Extracted from the article]

Summary: There is a large therapeutic gap in the treatment of sickle cell disease (SCD). Recent studies demonstrated the presence of pathophysiological and microbial changes in the intestine of patients with SCD. The intestinal microbes have also been found to regulate neutrophil ageing and possible basal activation of circulating neutrophils. Both aged and activated neutrophils are pivotal for the pathogenesis of vaso‐occlusive crisis in SCD. In this paper, we will provide an overview of the intestinal pathophysiological and microbial changes in SCD. Based on these changes, we will propose therapeutic approaches that could be investigated for treating SCD. [ABSTRACT FROM AUTHOR]

In transfusional iron overload, extra-hepatic iron distribution differs, depending on the underlying condition. Relative mechanisms of plasma non-transferrin bound iron ( NTBI) generation may account for these differences. Markers of iron metabolism (plasma NTBI, labile iron, hepcidin, transferrin, monocyte SLC40A1 [ferroportin]), erythropoiesis (growth differentiation factor 15, soluble transferrin receptor) and tissue hypoxia (erythropoietin) were compared in patients with Thalassaemia Major ( TM), Sickle Cell Disease and Diamond-Blackfan Anaemia ( DBA), with matched transfusion histories. The most striking differences between these conditions were relationships of NTBI to erythropoietic markers, leading us to propose three mechanisms of NTBI generation: iron overload (all), ineffective erythropoiesis (predominantly TM) and low transferrin-iron utilization ( DBA). [ABSTRACT FROM AUTHOR]

Treatment of post-transfusion hyperhaemolysis syndrome in Sickle Cell Disease with the anti-IL6R humanised monoclonal antibody Tocilizumab It is characterised by brisk haemolysis of both transfused and recipient red cells, also known as "By-stander" haemolysis, with a haemoglobin (Hb) drop below pre-transfusion levels, marked increase in serum ferritin (SF) and a fall in reticulocyte count. 1 Hb, haemoglobin, LDH, lactate dehydrogenase; PTHS, post-transfusion hyperhaemolysis syndrome; RTC, reticulocytes; SF, serum ferritin. [Extracted from the article]

In a seminal Lancet paper published in 1997, Dennis Lo, a clinical biochemist from Hong Kong working in Oxford with Jim Wainscoat, defined a technique that would transform the future of prenatal diagnosis (PND). This made it possible to simply collect a blood sample from a pregnant woman and identify unique fetal DNA characteristics from it, without needing invasive PND, which carries a 0-5-1% risk of miscarriage. To identify a fetal-origin point mutation from a sea of maternal DNA, 50% of which contain the same mutation, made it impossible to diagnose fetal disease without having access to DNA material from the father or siblings. [Extracted from the article]

The article highlights the survey conducted on an approach to Prophylactic red blood cell transfusion in pregnant women with sickle cell disease by health care professionals Canada and the United States. Topics discussed include to approach helps to improve maternal and fetal complications; risk associated with primary prophylaxis; and effect of disorder on maternal and neonatal outcomes.

Summary: Antenatal screening/testing of pregnant women should be carried out according to the guidelines of the National Health Service (NHS) Sickle Cell and Thalassaemia Screening Programme. Newborn screening and, when necessary, follow‐up testing and referral, should be carried out according to the guidelines of the NHS Sickle Cell and Thalassaemia Screening Programme. All babies under 1 year of age arriving in the United Kingdom should be offered screening for sickle cell disease (SCD). Preoperative screening for SCD should be carried out in patients from ethnic groups in which there is a significant prevalence of the condition. Emergency screening with a sickle solubility test must always be followed by definitive analysis. Laboratories performing antenatal screening should utilise methods that are capable of detecting significant variants and are capable of quantitating haemoglobins A2 and F at the cut‐off points required by the national antenatal screening programme. The laboratory must ensure a provisional report is available for antenatal patients within three working days from sample receipt. [ABSTRACT FROM AUTHOR]

Summary: RH diversity among patients and donors contributes to Rh immunization despite serologic Rh‐matched red cell transfusions. Anti‐D can occur in D+ patients with RHD variants that encode partial D antigens. Anti‐D has also been reported in patients with conventional RHD transfused primarily with units from Black donors who frequently have variant RHD. We report 48 anti‐D in 690 D+ transfused individuals with sickle cell disease, categorized here as expressing conventional D, partial D or D antigen encoded by RHD*DAU0. Anti‐D formed in a greater proportion of individuals with partial D, occurred after fewer D+ unit exposures, and remained detectable for longer than for those in the other categories. Among all anti‐D, 13 had clinical or laboratory evidence of poor transfused red cell survival. Most individuals with anti‐D were chronically transfused, including 32 with conventional RHD who required an average of 62 D− units/year following anti‐D. Our findings suggest that patients with partial D may benefit from prophylactic D− or RH genotype‐matched transfusions to prevent anti‐D. Future studies should investigate whether RH genotype‐matched transfusions can improve use of valuable donations from Black donors, reduce D immunization and minimize transfusion of D− units to D+ individuals with conventional RHD or DAU0 alleles. [ABSTRACT FROM AUTHOR]

Chronic red blood cell transfusion therapy (CRTT) prevents strokes and silent cerebral infarcts (SCIs) in children with sickle cell disease (SCD).[1] Deferasirox, a once-daily oral iron chelator, is used to manage transfusion-related iron overload. Deferasirox (Exjade, 25 mg/kg/day) was started in 2014 (ferritin 2232 ng/mL), held in 2015 (ferritin <500 ng/mL) and restarted in 2016 (ferritin 1050 ng/mL). Hyperammonemia and acute liver failure (ALF) have occurred in deferasirox-treated children with transfusion-dependent thalassaemia (TDT).[[2], [4]] We report two deferasirox-treated teens with SCD who developed hyperammonemia and ALF. [Extracted from the article]

Keywords: hyposplenism; pulmonary embolism; Sickle cell disease; splenectomy; venous thromboembolism EN hyposplenism pulmonary embolism Sickle cell disease splenectomy venous thromboembolism 793 796 4 05/05/23 20230515 NES 230515 Sickle cell disease (SCD) is the main cause of functional asplenia, due to splenic atrophy that is generally complete by five years of age in patients with severe genotypes (i.e., homozygous SS and S I i SP 0 sp -thalassaemia).[1] In addition, unpredictable complications, such as acute splenic sequestration (ASS) and hypersplenism, may require surgical splenectomy in up to 30% of patients.[2] Some authors have reported an increase in acute chest syndrome (ACS) and vaso-occlusive crisis (VOC) in the few years following the procedure in children,[3] but data on the long-term consequences of splenectomy in SCD adults are scarce. PATIENT CONSENT STATEMENT We have obtained verbal consent from the patient or patient's parent/guardian. This study showed that SCD patients of S I i SP 0 sp genotype or with an associated -thalassaemia trait were more likely to be splenectomized than SS patients. VTEs included deep vein thrombosis (DVT) and pulmonary embolism (PE) while central venous catheter (CVC)-related thromboses were excluded. [Extracted from the article]

Keywords: sickle-cell anemia; mental disorders; addictive behaviour; hospital emergency service; hospitalisation EN sickle-cell anemia mental disorders addictive behaviour hospital emergency service hospitalisation e21 e23 3 03/31/20 20200401 NES 200401 Psychiatric disorders as a whole are associated with increased health consumption in children with sickle-cell disease (SCD) (Myrvik I et al. i , [4], [5]). The cumulative duration of emergency visits and hospitalisations was 14-3 days per patient-year [interquartile range (IQR): 7-6-42-4] in the psychiatric disorders group and 5-7 (IQR: 2-7-11-9) in the control group ( I P i < 0-001, Table). This difference was mostly due to the higher number of emergency visits and of emergency hospitalisations per patient-year in patients with psychiatric comorbidities (Table). [Extracted from the article]

The article discusses research which examined the effect of regulated automated red cell exchange transfusion (ARCET) in male patients with sickle cell disease (SCD) and recurrent stuttering priapism (SP), an unwanted erection. Topics discussed include management measures for SP, evolution of SP into acute major priapism (MP) which carries a risk of erectile dysfunction (ED), patient characteristics and haematological parameters and improvement experienced by patients after undergoing ARCET.

Summary: Ischaemic stroke is a common complication of sickle cell disease (SCD) and without intervention can affect 11% of children with SCD before the age of 20. Within the Trans‐Omics for Precision Medicine (TOPMed), a genome‐wide association study (GWAS) of ischaemic stroke was performed on 1333 individuals with SCD from Brazil (178 cases, 1155 controls). Via a novel Cox proportional‐hazards analysis, we searched for variants associated with ischaemic stroke occurring at younger ages. Variants at genome‐wide significance (p < 5 × 10−8) include two near genes previously linked to non‐SCD early‐onset stroke (<65 years): ADAMTS2 (rs147625068, p = 3.70 × 10−9) and CDK18 (rs12144136, p = 2.38 × 10−9). Meta‐analysis, which included the independent SCD cohorts Walk‐PHaSST and PUSH, exhibited consistent association for variants rs1209987 near gene TBC1D32 (p = 3.36 × 10−10), rs188599171 near CUX1 (p = 5.89 × 10−11), rs77900855 near BTG1 (p = 4.66 × 10−8), and rs141674494 near VPS13C (1.68 × 10−9). Findings from this study support a multivariant model of early ischaemic stroke risk and possibly a shared genetic architecture between SCD individuals and non‐SCD individuals younger than 65 years. [ABSTRACT FROM AUTHOR]

Summary: Delayed haemolytic transfusion reaction (DHTR) is a life‐threatening haemolytic anaemia following red blood cell transfusion in patients with sickle cell disease, with only scarce data in children. We retrospectively analysed 41 cases of DHTR in children treated between 2006 and 2020 in a French university hospital. DHTR manifested at a median age of 10.5 years, symptoms occurred a median of 8 days after transfusion performed for an acute event (63%), before surgery (20%) or in a chronic transfusion programme (17%). In all, 93% of patients had painful crisis. Profound anaemia (median 49 g/L), low reticulocyte count (median 140 ×109/L) and increased lactate dehydrogenase (median 2239 IU/L) were observed. Antibody screening was positive in 51% of patients, and more frequent when there was a history of alloimmunisation. Although no deaths were reported, significant complications occurred in 51% of patients: acute chest syndrome (12 patients), cholestasis (five patients), stroke (two patients) and kidney failure (two patients). A further transfusion was required in 23 patients and corticosteroids were used in 21 to reduce the risk of additional haemolysis. In all, 13 patients subsequently received further transfusions with recurrence of DHTR in only two. The study affords a better overview of DHTR and highlights the need to establish guidelines for its management in children. [ABSTRACT FROM AUTHOR]

Summary: Brain injury is a common complication of sickle cell anaemia (SCA). White matter (WM) and cortical and subcortical grey matter (GM), structures may have reduced volume in patients with SCA. This study focuses on whether silent cerebral infarction (SCI), vasculopathy or anaemia affects WM and regional GM volumes in children living in Africa. Children with SCA (n = 144; aged 5–20 years; 74 male) and sibling controls (n = 53; aged 5–17 years; 29 male) underwent magnetic resonance imaging. Effects of SCI (n = 37), vasculopathy (n = 15), and haemoglobin were assessed. Compared with controls, after adjusting for age, sex and intracranial volume, patients with SCA had smaller volumes for WM and cortical, subcortical and total GM, as well as bilateral cerebellar cortex, globus pallidus, amygdala and right thalamus. Left globus pallidus volume was further reduced in patients with vasculopathy. Putamen and hippocampus volumes were larger in patients with SCA without SCI or vasculopathy than in controls. Significant positive effects of haemoglobin on regional GM volumes were confined to the controls. Patients with SCA generally have reduced GM volumes compared with controls, although some subcortical regions may be spared. SCI and vasculopathy may affect the trajectory of change in subcortical GM and WM volume. Brain volume in non‐SCA children may be vulnerable to contemporaneous anaemia. [ABSTRACT FROM AUTHOR]

Summary: Hypoxia‐mediated red blood cell (RBC) sickling is central to the pathophysiology of sickle cell disease (SCD). The signalling nucleoside adenosine is thought to play a significant role in this process. This study investigated expression of the erythrocyte type 1 equilibrative nucleoside transporter (ENT1), a key regulator of plasma adenosine, in adult patients with SCD and carriers of sickle cell trait (SCT). Relative quantitative expression analysis of erythrocyte ENT1 was carried out by Western blot and flow cytometry. Patients with SCD with steady state conditions, either with SS or SC genotype, untreated or under hydroxycarbamide (HC) treatment, exhibited a relatively high variability of erythrocyte ENT1, but with levels not significantly different from normal controls. Most strikingly, expression of erythrocyte ENT1 was found to be significantly decreased in patients with SCD undergoing painful vaso‐occlusive episode and, unexpectedly, also in healthy SCT carriers. Promoting hypoxia‐induced adenosine signalling, the reduced expression of erythrocyte ENT1 might contribute to the pathophysiology of SCD and to the susceptibility of SCT individuals to altitude hypoxia or exercise to exhaustion. [ABSTRACT FROM AUTHOR]

Summary: Individuals with sickle cell disease (SCD) have historically been considered underweight. Despite increasing body mass index (BMI) in the general population, the prevalence of overweight and obese status remains unclear in the adult SCD population. Our primary aim was to determine the prevalence of overweight and obese status and to identify associations between BMI, demographic, and clinical characteristics. We conducted an analysis of abstracted electronic health record data and patient‐reported outcomes from the Sickle Cell Disease Implementation Consortium registry; individuals aged 20–45 years were included. The median (interquartile range) BMI for the 1664 adults in this analysis was 23.9 (21.1–28) kg/m2. In this cohort, 42.9% had a BMI of >25 kg/m2 (Centers for Disease Control and Prevention definition of overweight/obese). In multivariable analysis, higher odds of being overweight or obese were associated with female gender, older age, college education, private insurance, and hypertension diagnosis. Higher odds of a BMI of >25 kg/m2 were observed in individuals with HbSC or HbSβ+ thalassaemia regardless of hydroxycarbamide (hydroxyurea) exposure (odds ratio [OR] 3.4, p < 0.0001) and HbSS or HbSβ0 thalassaemia exposed to hydroxycarbamide (OR 1.6, p = 0.0003) compared to those with HbSS or HbSβ0 thalassaemia with no hydroxycarbamide exposure. These data highlight the importance of early identification, prevention, and intervention for increasing BMI to reduce obesity‐related complications that may impact SCD‐related complications. [ABSTRACT FROM AUTHOR]

It is of note that, despite the fact that eight of the 15 patients with SCA with AID received anti-inflammatory and/or immunosuppressant/immunomodulatory drugs, they still had a greater inflammatory level than patients without AID. Indeed, the greater inflammatory state caused by the presence of AID in patients with SCA, as shown by the greater CRP level and WBC count, would be the cause of the increased fibrinogen level and, thus, RBC aggregation. RBC aggregation is known to strongly modulate blood viscosity at low shear rates.[12] Indeed, the increased blood viscosity at the lowest shear rate found in patients with AID would be due to the greater RBC aggregation compared to the Control group. [Extracted from the article]

Summary: Despite recent developmental screening guidelines, rates of neurodevelopmental disorders (NDDs) remain lower than expected in children with sickle cell disease (SCD). A retrospective chart review identified 276 eligible patients; 214 charts were available for developmental screening and 207 charts for autism‐specific screening. Developmental surveillance/screening was conducted in 70% of charts and autism‐specific screening in 19% of charts. Validated tools were used in 32% of developmental screenings and 92% of autism‐specific screenings. Many children (57%) were screened outside recommended ages. In conclusion, children with SCD are not regularly receiving appropriate developmental screening and surveillance by their healthcare providers. [ABSTRACT FROM AUTHOR]

Summary: Children diagnosed with sickle cell disease (SCD) are at risk of the development of neurobehavioural problems early in life. Specific impairments in executive function skills, including working memory, have been documented in school‐aged children with SCD. These executive skills are known to strongly contribute to early academic skills and preparedness for entering kindergarten. This study examined working memory and school readiness in preschool children with SCD compared to a healthy control group matched for race, sex and parent education. A total of 84 patients diagnosed with SCD (61.9% haemoglobin [Hb]SS/HbSβ0‐thalassaemia) and 168 controls completed testing. The mean (SD) ages of patients and controls at testing were 4.53 (0.38) and 4.44 (0.65) years respectively. The SCD group performed worse than controls on measures of executive function, working memory and school readiness (p < 0.01; Cohen's D range: 0.32–0.39). Measures of working memory were associated with school readiness after accounting for early adaptive development. Multiple linear regression models among patients diagnosed with SCD revealed that college education of the primary caregiver was positively associated with school readiness (p < 0.001) after controlling for sex, genotype, age and early adaptive development. These results highlight the need to implement school readiness interventions in young children diagnosed with SCD emphasising executive function skills. [ABSTRACT FROM AUTHOR]

The significant correlation between COVID-19 and influenza vaccination suggests that immunisation hesitancy is not specific to the newly developed COVID-19 vaccine. Sickle cell disease (SCD) is caused by homozygous or compound heterozygous inheritance of mutations in the beta-globin chains.1,2 Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) may potentially lead to severe complications in patients with SCD due to immunocompromise.3,4 The clinical course of COVID-19 infection in SCD has been described in larger cohorts with COVID-19 severity varying widely among patients.5-8 The purpose of this study was to investigate COVID-19 vaccination9-11 patterns in SCD. Demographic information, COVID-19 vaccination status, COVID-19 infection, healthcare encounters and influenza vaccination history were collected by the primary and co-investigators. The COVID-19 vaccines appear to not cause significant side-effects in this patient population, and completion of the primary series of COVID-19 vaccinations decreased the infection risk by 70% before the Omicron surge. [Extracted from the article]

Summary: There have been limited investigations into exercise in sickle cell disease (SCD). In the general population, health is reflected in general physical fitness. It is unclear if the same associations are seen in people with SCD. Here, we report a cross‐sectional assessment of two important measures of physical fitness, muscle strength and cardiorespiratory endurance, in adults with SCD. A total of 29 adults with SCD (aged 24–62 years; 72% female) completed cardiopulmonary and muscular strength testing using a cycle ergometer and an isokinetic dynamometer. Adults with SCD had lower median values for cardiorespiratory endurance (the median [interquartile range, IQR] peak oxygen uptake [VO2] 16.1 [6.3] vs. 42.65 [11.3] ml/kg/min, p < 0.001) and knee strength (median [IQR] flexor torque 26.91[22.5] vs. 55.6 [22.7] Nm, p < 0.001) compared to controls and predicted values. Interestingly, there was a very positive association between muscular strength and peak VO2 values for adults with SCD (r = 0.53, p = 0.003) suggesting these values may be useful in determining cardiopulmonary health. [ABSTRACT FROM AUTHOR]

Treatment of sickle cell disease by increasing oxygen affinity of hemoglobin. The departure of a second O SB 2 sb from Hb signals that local oxygen is becoming sparse, and as a result the Hb switches over to a state of lower oxygen affinity, anticipating future demands. Sickle hemoglobin oxygen affinity-shifting strategies have unequal cerebrovascular risks. Keywords: VOXELOTOR; sickle cell; sigmoidal oxygen EN VOXELOTOR sickle cell sigmoidal oxygen 13 15 3 06/27/23 20230701 NES 230701 Voxelotor is designed to impeded the polymerization of sickle haemoglobin. [Extracted from the article]

Four and three patients in each group (respectively) were on continuous HC therapy upon inclusion, and one patient in the non-intervention arm continued taking HC (20 mg/kg/day) throughout the study (the other patients in this group did not take their medication to the ER). Safe use of hydroxycarbamide in sickle cell disease patients hospitalized for painful vaso-occlusive episodes during the randomized, open-label HELPS study. [Extracted from the article]

Anti-spike antibody levels significantly increased by exposure number (i.e., vaccination and/or infection, I R i SP 2 sp = 0.34, I p i < 0.001), but anti-nucleocapsid antibody levels did not (Figure 1E,F). Anti-spike and anti-nucleocapsid antibody levels were quantified in 36 patients with sickle cell disease (SCD) and 22 control patients without SCD seen in the same haematology adult and paediatric clinics. All SCD participants and 95% of controls had detectable anti-spike protein antibodies; 21 (58.3%) and 11 (50.0%) had anti-nucleocapsid antibodies, respectively. Keywords: antibodies; coronavirus 2019 (COVID-19); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); sickle cell disease; splenic function EN antibodies coronavirus 2019 (COVID-19) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sickle cell disease splenic function 680 683 4 08/10/22 20220815 NES 220815 Antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or vaccination reduces infection risk.1 In the United States, people with sickle cell disease (SCD) have experienced considerable complications from SARS-CoV-2 infection.2,3 Functional hyposplenia, asplenia, or splenectomy in SCD can increase pathogen susceptibility and reduce vaccine responsiveness.4 We evaluated serum antibody levels for anti-nucleocapsid antibodies from past infection and anti-spike antibodies from vaccination and/or past infection in people with SCD. [Extracted from the article]

Fat embolism syndrome (FES) is a severe but underdiagnosed complication of sickle cell disease (SCD) associated with very high mortality and morbidity. 2022; 36 (10): 3859 - 62. 12 Bosch A, Watad S, Willmott S, McKinnon NK, Malcolmson C, Kirby M. Identifying and treating severe bone marrow necrosis and fat embolism syndrome in pediatric patients with sickle cell disease: a case report. [Extracted from the article]

Summary: Adults with sickle cell disease (SCD) are at risk for cognitive impairment, which causes significant morbidity. Guidelines support routine cognitive screening, but no screening test is validated in this population. We explored the Montreal Cognitive Assessment (MoCA) as a possible screening test in SCD. We administered the MoCA; a literacy test, the Wide Range Achievement Test, fourth edition (WRAT‐4); and a health literacy test, the Shortened Test of Functional Health Literacy in Adults (S‐TOFHLA) to adults with SCD and gathered clinical variables through chart review. Spearman's rho, Mann–Whitney, and Kruskal–Wallis tests and quantile regression models were used. Among our sample of 49 adults with SCD, the median MoCA score was 25.0 [interquartile range (IQR) 22.0–28.0]. Higher educational attainment was associated with MoCA scores (p = 0.001). In multivariable models, MoCA scores were associated with S‐TOFHLA (p = 0.001) and WRAT‐4 Reading (p = 0.002) scores, and overt stroke (p = 0.03) at the median. This pilot study adds to the limited literature of cognitive screening tests in adults with SCD and demonstrates a relationship between MoCA scores and measures of literacy and health literacy. The MoCA is a promising option for briefly screening for cognitive impairment in adults with SCD, though further study is needed to confirm its validity. [ABSTRACT FROM AUTHOR]

Summary: Red blood cells (RBCs) lose plasma membrane in the spleen as they age, but the cells and molecules involved are yet to be identified. Sickle cell disease and infection by Plasmodium falciparum cause oxidative stress that induces aggregates of cross‐linked proteins with N‐linked high‐mannose glycans (HMGs). These glycans can be recognised by mannose‐binding lectins, including the mannose receptor (CD206), expressed on macrophages and specialised phagocytic endothelial cells in the spleen to mediate the extravascular haemolysis characteristic of these diseases. We postulated this system might also mediate removal of molecules and membrane in healthy individuals. Surface expression of HMGs on RBCs from patients who had previously undergone splenectomy was therefore assessed: high levels were indeed observable as large membrane aggregates. Glycomic analysis by mass spectrometry identified a mixture of Man5‐9GlcNAc2 structures. HMG levels correlated well with manual pit counts (r = 0.75–0.85). To assess further whether HMGs might act as a splenic reticuloendothelial function test, we measured levels on RBCs from patients with potential functional hyposplenism, some of whom exhibited high levels that may indicate risk of complications. [ABSTRACT FROM AUTHOR]

Summary: Sickle cell disease (SCD) is an inherited blood disorder that is associated with developmental delays and neurocognitive deficits. This review details key findings related to neurocognitive outcomes for children and adults with emphasis on the impact of neurological correlates and disease severity. Associations between neurocognition, demographic factors and social determinants of health are also reviewed. Emerging literature has reported on the neurocognitive impact of SCD in children and adolescents in Africa and Europe, including children from immigrant communities. Neurocognitive deficits are linked to poor functional outcomes, including transition from paediatric to adult care, medication adherence and unemployment. Integrating neuropsychology into multidisciplinary care for individuals with SCD can assist with identification and management of neurocognitive concerns, intervention development, individualized care plan development and continued multidisciplinary research. [ABSTRACT FROM AUTHOR]

Inflammation, leucocytes, sickle cell disease, CD206, low-density neutrophils, vaso-occlusion Accelerated low-density neutrophil transition in sickle cell anaemia may contribute to disease pathophysiology Keywords: CD206; inflammation; leucocytes; low-density neutrophils; sickle cell disease; vaso-occlusion EN CD206 inflammation leucocytes low-density neutrophils sickle cell disease vaso-occlusion 232 235 4 04/19/22 20220415 NES 220415 Neutrophil plasticity is increasingly recognised, and granulocyte subsets such as the low-density neutrophils (LDNs) reportedly participate in self-resolving inflammation and cancer progression.1,2 Sickle cell anaemia (SCA) is an inherited haemolytic disorder associated with chronic inflammation SP S1 sp and extensive neutrophil functional heterogeneity, whereby augmented neutrophil recruitment to the vascular wall can play a triggering role in vaso-occlusive mechanisms.3-5 We aimed to determine whether normal-density neutrophil (NDN) to LDN transition is modulated in SCA, and to characterise this leucocyte subset further, with a view to determining a potential role in the disease's pathophysiology. [Extracted from the article]

Summary: There are limited data on contemporary outcomes for women with sickle cell disease (SCD) in pregnancy. We conducted a single‐site matched cohort study, comparing 131 pregnancies to women with SCD between 2007 and 2017 to a comparison group of 1310 pregnancies unaffected by SCD. Restricting our analysis to singleton pregnancies that reached 24 weeks of gestation, we used conditional Poisson regression to estimate adjusted risk ratios (aRRs) for perinatal outcomes. Infants born to mothers with SCD were more likely to be small for gestational age [aRR 1·69, 95% confidence interval (CI) 1·13–2·48], preterm (aRR 2·62, 95% CI 1·82–3·78) and require Neonatal Unit (NNU) admission (aRR 3·59, 95% CI 2·18–5·90). Pregnant women with SCD were at higher risk of pre‐eclampsia/eclampsia (aRR 3·53, 95% CI 2·00–6·24), more likely to receive induction of labour (aRR 2·50, 95% CI 1·82–1·76) and caesarean birth (aRR 1·44, 95% CI 1·18–1·76). In analysis stratified by genotype, the risk of adverse outcomes was highest in haemoglobin SS (HbSS) pregnancies (n = 80). There was no strong evidence that haemoglobin SC (HbSC) pregnancies (n = 46) were at higher risk of preterm birth, caesarean delivery, or NNU admission. Pre‐eclampsia/eclampsia was more frequently observed in HbSC pregnancies. Despite improvements in the care of pregnant women with SCD, the increased risk of adverse perinatal outcomes remains. [ABSTRACT FROM AUTHOR]

Summary: Delayed haemolytic transfusion reaction (DHTR) is a potentially life‐threatening complication of red blood cell (RBC) transfusions in sickle cell disease (SCD) and is classically induced by reactivation of previously formed antibodies. Improved antigenic matching has reduced alloimmunization and may reduce DHTR risk. We conducted a retrospective cohort study to investigate the incidence rate of DHTR in SCD patients receiving extended matched units (ABO/RhDCcEe/K/Fya/Jkb/S). Occasional transfusion episodes (OTE) between 2011 and 2020 were reviewed for occurrence of DHTR symptoms using four screening criteria: decreased Hb, increased lactate dehydrogenase (LDH), pain, and dark urine. We included 205 patients who received a cumulative number of 580 transfusion episodes of 1866 RBC units. During follow‐up, 10 DHTR events were observed. The incidence rate of DHTR was 13·8/1000 OTEs [95% confidence interval (CI): 7·37–22·2], with a cumulative incidence of 15·2% (95% CI: 8·4–24·0%) after 25 patients having received RBC units. One DHTR event was fatal (10%). Symptoms were misdiagnosed in four DHTR events (40%) as other acute SCD complications. Despite a lower incidence rate compared to most other studies, the incidence rate of DHTR in SCD remains high, in spite of extended matching of donor RBCs. Increased awareness of DHTR is of utmost importance to facilitate early diagnosis and, consequently, improve outcome. [ABSTRACT FROM AUTHOR]

The article presents a research on longitudinal evaluation of cerebral white matter hyperintensities (WMH) lesion volume in children with sickle cell disease (SCD). Topics discussed include magnetic resonance imaging (MRI) as a part of SCD clinical care; measuring of white matter lesion volume by drawing all lesions on each fluid attenuation inversion recovery (FLAIR) image; and lesion volume was increased in some patients and it remained the same in other patients.

Summary: We examined heart rate variability (HRV) during exercise testing in 20 children with sickle cell anaemia (SCA) and 12 controls. Subjects achieved lower median HRV at peak exercise [standard deviation of R‐wave to R‐wave intervals (SDNN), 2·3 vs 2·9 ms, P = 0·027; logarithmic transformation of high frequency power (lnHF), 0·9 vs 1·3 ln(ms2), P = 0·047] and had lower post‐exercise HRV across minute‐by‐minute analysis of recovery. After adjustment for haemoglobin, fitness and SCA status, subjects had lower HRV at the end of recovery with differences increasing as baseline HRV increased. Further investigation of HRV and exercise safety in SCA is warranted. [ABSTRACT FROM AUTHOR]

Summary: Clinical and genetic factors have been reported as influencing the development of sickle cell nephropathy (SCN). However, such data remain limited in the paediatric population. In this cross‐sectional study, we enrolled 361 sickle cell disease children from the Democratic Republic of Congo. Participants were genotyped for the beta (β)‐globin gene, apolipoprotein L1 (APOL1) risk variants, and haem oxygenase‐1 (HMOX1) GT‐dinucleotide repeats. As markers of kidney damage, albuminuria, hyperfiltration and decreased estimated glomerular filtration with creatinine (eGFRcr) were measured. An association of independent clinical and genetic factors with these markers of kidney damage were assessed via regression analysis. Genetic sequencing confirmed sickle cell anaemia in 326 participants. Albuminuria, hyperfiltration and decreased eGFRcr were present in 65 (20%), 52 (16%) and 18 (5·5%) patients, respectively. Regression analysis revealed frequent blood transfusions, indirect bilirubin and male gender as clinical predictors of SCN. APOL1 high‐risk genotype (G1/G1, G2/G2 and G1/G2) was significantly associated with albuminuria (P = 0·04) and hyperfiltration (P = 0·001). HMOX1 GT‐dinucleotide long repeats were significantly associated with lower eGFRcr. The study revealed a high burden of kidney damage among Congolese children and provided evidence of the possible role of APOL1 and HMOX1 in making children more susceptible to kidney complications. [ABSTRACT FROM AUTHOR]

Summary: Hydroxyurea (hydroxycarbamide) (HU) for sickle cell anaemia (SCA) is underutilised. Case management is an evidence‐based health management strategy and in this regard patient navigators (PNs) may provide case management for SCA. We hypothesised that HU‐eligible patients exposed to PNs would have improved indicators of starting HU and HU adherence. We randomised 224 HU‐eligible SCA adults into the Start Healing in Patients with Hydroxyurea (SHIP‐HU) Trial. All patients received care from trained physicians using standardised HU prescribing protocols. Patients in the Experimental arm received case management and education from PNs through multiple contacts. All other patients were regarded as the Control arm and received specialty care alone. Study physicians were blinded to the study arms and did not interact with PNs. At baseline, 6 and 12 months we assessed and compared laboratory parameters and HU adherence indicators. Experimental patients had higher 6‐month mean fetal haemoglobin (HbF) levels than controls. But at 12 months, mean HbF was similar, as were white blood cell count, absolute neutrophil count, total haemoglobin, platelet count and mean corpuscular volume. At 12 months there were fewer experimental patients missing HU doses than controls (mean 1·8 vs. 4·5, P = 0·0098), and more recent HU prescriptions filled than for controls (mean 53·8 vs. 92 days, median 27·5 vs. 62 days, P = 0·0082). Mean HU doses were largely similar. We detected behavioural improvements in HU adherence but no haematological improvements by adding PNs to specialty care. [ABSTRACT FROM AUTHOR]

Summary: Alpha haemoglobin‐stabilising protein (AHSP) is a key chaperone synthesised in red blood cell (RBC) precursors. Many studies have reported AHSP as a potential biomarker of various diseases. AHSP gene expression has been studied in detail, but little is known about AHSP protein levels in RBCs. We investigated the AHSP concentration of RBC lysates from control subjects (n = 10) and patients with sickle cell anaemia (SCA) with (n = 10) and without (n = 12) hydroxycarbamide (HC) treatment, to evaluate the clinical relevance of AHSP in SCA. We developed a sandwich enzyme‐linked immunosorbent assay method, with which we were able, for the first time, to determine the mean AHSP concentration in control RBC lysates (0·82 µg/ml). The AHSP concentration (2·23 µg/ml) was significantly higher in untreated patients with the SS genotype than in controls. The AHSP concentration decreased significantly on HC treatment (1·50 µg/ml) but remained significantly higher than that in controls. A strong positive correlation was observed between the AHSP concentration and the α‐haemoglobin pool with the three groups of subjects pooled into a single group. Our present findings indicate that AHSP concentration can be considered a candidate biomarker for monitoring HC responses in patients with SCA and suggest a role for AHSP in various RBC diseases. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is a devastating and under‐recognised global child health issue affecting over 300,000 infants annually, with the highest prevalence in India and sub‐Saharan Africa. Most affected infants born in low‐ and middle‐income countries (LMIC) lack access to SCD testing and die from complications in the first years of life without a formal diagnosis. The majority of deaths are preventable with early diagnosis and provision of inexpensive interventions. Despite global recognition of the urgent need, expansion of SCD newborn screening (NBS) programmes beyond the pilot stage has been obstructed by a dependence on an expensive and logistically challenging centralised laboratory testing model. Recently, several point‐of‐care tests (POCT) for SCD have been developed with promising field validation studies. Here, we summarise the state of POCT for SCD, review barriers and unanswered questions, and discuss optimal strategies for utilising POCT to address the growing global burden of SCD. There is an urgent need to prospectively evaluate the ability of POCT to reduce the morbidity and high early mortality of SCD. To impact a sustainable reduction to this end, it is essential to link a diagnosis with comprehensive SCD care, including wide and affordable access to affordable hydroxycarbamide therapy. [ABSTRACT FROM AUTHOR]