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.

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Key Points The 3 established HbF genetic loci can be summarized into 1 quantitative variable, g(HbF), in SCD and influence markers of SCD severity. g(HbF) provides a quantitative marker for the genetic component of HbF% variability, potentially useful in genetic and clinical studies in SCD.

The antiphospholipid syndrome (APS) is the association of thrombosis and recurrent pregnancy loss and/or pregnancy morbidity with persistent antiphospholipid antibodies (aPL). Increased complement activation has been implicated in the pathogenesis of APS in animal models. It was our objective to evaluate complement activation in patients with aPL or primary antiphospholipid syndrome (PAPS). We measured complement activation products, fragments Bb and C3a-desArg by ELISA in 186 aPL/PAPS patients and 30 healthy controls. All patients with aPL had significantly increased levels of complement activation products. Fragment Bb levels (mean, 95% CI); (thrombotic APS 0.54 units/ml, 0.31-0.83, obstetric APS 0.60 units/ml,0.39-1.02, isolated aPL 0.48 units/ml, 0.29-0.85, overall 0.39 units/ml, 0.33-0.47) and C3a-desArg levels (mean, 95% CI): (thrombotic APS 261 ng/ml, 219-311, obstetric APS 308 ng/ml, 243-391, isolated aPL 258 ng/ml, 193-337, overall 225 ng/ml, 202-251) were significantly higher compared to controls (fragment Bb 0.06 units/ml, 0.03-0.11, C3a-desArg 69 ng/ml, 50-92). There were correlations between Fragment Bb and C3a-desArg levels in all patients with aPL. Receiver operator characteristic (ROC) analysis showed increased fragment Bb and C3a-desArg levels had strong associations with the presence of persistent lupus anticoagulant (area under ROC: Bb 0.89, and C3a-desArg 0.90), dual and triple aPL positivity (Bb 0.71-0.82, C3a-desArg 0.71-0.80) but not with high titre anti-cardiolipin antibodies (Bb 0.62, C3a-desArg 0.65), or anti β2-glycoprotein 1 antibodies (Bb 0.66, C3a-desArg 0.67). Complement activation is present in all patient groups within this large cohort of patients aPL. This suggests it may have a major role in the pathogenesis of APS and merits further study.

Background Benign ethnic neutropenia (BEN) is the most common cause of chronic neutropenia seen in individuals of African, Middle Eastern and West Indian descent. This phenotype is broadly defined by an absolute neutrophil counts (ANC) below 1.8 × 109 cells/L in the absence of other causes, without an increased risk of infection. BEN has been implicated as a potential source of disparity in patients treated with clozapine, the antipsychotic of choice in treatment-resistant schizophrenia. Our main objective was to examine the current level of BEN recognition in a cohort of patients treated with clozapine and the potential impact of unidentified BEN on the initiation and maintenance of clozapine treatment. Methods This was an observational, retrospective analysis of patients registered with clozapine haematological monitoring systems in two large mental health trusts, chosen because they serve an ethnically diverse population. The first objective was to establish certified BEN prevalence in current users of clozapine. The second objective was to explore the stage of treatment at which BEN was identified. The third objective was to evaluate the extent of unrecognised BEN in patients registered on the Central Non-Rechallenge Database (CNRD), a database for patients whose haematological parameters fall below set thresholds when receiving clozapine treatment, meaning they cannot ordinarily be prescribed clozapine again. Results The study population comprised of 2020 patients on the clozapine register. 111 patients were monitored under BEN criteria. BEN was mostly identified after a below threshold haematological result or clozapine rechallenge (68%) compared to at clozapine initiation (32%). Eight of the 18 (42%) black patients registered on the CNRD were classified as BEN after assessment by a haematologist. Of these 8 patients, none would have met CNRD criteria again if monitored with BEN criteria at clozapine initiation. Conclusions Current evidence suggests that BEN remains an uncommonly recognised haematological phenotype. Improved timely identification of BEN will reduce unnecessary interruption or discontinuation of clozapine treatment. Our results suggest consideration should also be given to determining BEN status prior to initiating clozapine. Moreover, adoption of current FDA BEN monitoring criteria in the UK may further reduce clozapine discontinuation due to perceived neutropenia as drug toxicity, particularly in treatment-refractory schizophrenia patients.

Objectives To investigate whether resistance to annexin A5 anticoagulant activity (AnxA5) occurs in women with histories for obstetric complications of antiphospholipid syndrome (Obs-APS) and whether this correlates with antibody recognition of domain 1 of β2- glycoprotein. Study Design 136 women with antiphospholipid antibodies, including 70 with histories for Obs-APS, and 30 controls, were investigated. Results Women with Obs-APS showed resistance to AnxA5 activity (median (range) 216% (130-282%) vs. controls 247% (217-283%), p<0.0001) and elevated levels of anti-domain I IgG (OD: median (range) 0.056 (0.021-0.489) vs. 0.042 (0.020-0.323); p=0.002). Those in the lowest tertile of AnxA5 anticoagulant ratios had an OR for Obs-APS APS of 58.0 (95% CI 3.3-1021.5). There was an inverse correlation between levels of annexin A5 anticoagulant activity and anti-domain I IgG. Conclusions Resistance to AnxA5 anticoagulant activity is associated with antibody recognition of domain I of β2GPI and identifies a subset of women with histories for Obs-APS.

α‐Thalassemia is one of the most important genetic modulators of sickle cell disease (SCD). Both beneficial and detrimental effects have been described previously. We use a 12‐year data set on a large cohort of patients with HbSS (n = 411) and HbSC (n = 146) to examine a wide range of these clinical and laboratory associations. Our novel findings are that α‐thalassemia strongly reduces erythrocyte potassium chloride co‐transporter (KCC) activity in both HbSS and HbSC (p = .035 and p = .00045 respectively), suggesting a novel mechanism through which α‐thalassemia induces a milder phenotype by reducing red cell cation loss. This may be particularly important in HbSC where reduction in mean cell hemoglobin concentration is not seen and where KCC activity has previously been found to correlate with disease severity. Additionally, we show that α‐thalassemia not only increases hemoglobin in patients with HbSS (p = .0009) but also reduces erythropoietin values (p = .0005), demonstrating a measurable response to improved tissue oxygenation. We confirm the reno‐protective effect of α‐thalassemia in patients with HbSS, with reduced proteinuria (p = .003) and demonstrate a novel association with increased serum sodium (p = .0004) and reduced serum potassium values (p = 5.74 × 10−10). We found patients with α‐thalassemia had a reduced annualized transfusion burden in both HbSS and HbSC, but α‐thalassemia had no impact on annualized admission rates in either group. Finally, in a larger cohort, we report a median survival of 62 years in patients with HbSS (n = 899) and 80 years in those with HbSC (n = 240). α‐thalassemia did not influence survival in HbSS, but a nonsignificant trend was seen in those with HbSC.

Sickle cell anaemia (SCA) is a recognised prothrombotic condition. 1 The incidence rate for first venous thromboembolism (VTE) is reported at 5.2 events/1000 person years with a cumulative incidence of 11.3% by age 40 years. 2,3 This is fifty times higher than the quoted VTE risk for under 40 year olds. 4 Long-term exchange blood transfusion (EBT) is an important therapeutic option, however, use of an indwelling venous access device (IVAD) may be necessary to maintain venous access. The attendant risk of catheter related thrombosis (CRT) is influenced by patient, disease and catheter characteristics. 5 Previous reports regarding CRT and IVADs in the SCA population, listed in Table I, often grouped external and internal, and single and dual lumen devices together, making analysis challenging. The per-person thrombotic rate in adults ranges from 19-41%, 6-10 whilst in children this rate is 0-10%. [10][11][12] One study reported no significant difference in CRT rates between dual (23%) or single (33%) lumen devices, 10 whilst another reported increased rates with dual lumen devices in their pediatric population (25% vs. 0%), although these patients were also older and having automated erythrocytopheresis as opposed to manual exchange. 13 By comparison, in the cancer population the rate is only 3-4%. 5 Thus, adults with SCA are a high risk group for CRT.We performed a five year retrospective analysis of IVADs