Hemophilia A and B are rare X-linked bleeding disorders caused by coagulation factor deficiencies, leading to joint bleeding, synovial hypertrophy and chronic hemophilic arthropathy marked by progressive cartilage and bone damage. Musculoskeletal issues remain the primary source of morbidity in people with hemophilia (PwH). Despite significant advances in prophylactic therapies, joint pain, functional limitations, and deterioration persist. The long-term impact of novel treatments on joint health and physical activity levels remains incompletely understood. Early detection and prevention of damage is challenging, highlighting the need for highly sensitive diagnostic tools to identify subclinical changes before irreversible damage occurs. Pain management, currently adapted from other conditions, does not fully meet the unique needs of PwH. Research into targeted pain relief, synovial hypertrophy management, and cartilage regeneration is crucial. Addressing unmet needs in diagnosis, treatment, and management requires collaboration between clinical and research communities to improve care effectiveness and enhance the quality of life for PwH.

BackgroundDetection of sickle cell disease (SCD) could be improved with greater use of point-of-care testing (POCT). This review assessed the accuracy of POCTs for SCD in children and adolescents. MethodsWe systematically searched EMBASE, PubMed, Cochrane libraries, registries and conference proceedings from inception to 28th February 2023. We included cross-sectional and case-control studies that tested for SCD using POCTs and reference tests in individuals aged 0–19. We conducted meta-analysis to assess sensitivity and specificity of individual POCTs. FindingsThe review included 31 studies overall, with 20 covering lateral flow immunoassays (LFIAs) and four covering micro-engineered electrophoresis. When detecting homozygous SCD, the pooled sensitivity and specificity of the included LFIAs and micro-engineered electrophoresis POCTs was 92 % or higher in all individual meta-analyses. Sensitivities and specificities were also nearly 100 % when detecting haemoglobin SC disease for these POCTs. InterpretationPOCTs could be used to accurately diagnose SCD.

The acute pain crisis (APC) is the commonest complication of sickle cell disease (SCD). Severe episodes may require treatment in hospital with strong opioid analgesic drugs, combined with additional supportive care measures. Guidelines for APC management have been produced over the past two decades gathering evidence from published studies, expert opinion, and patient perspective. Unfortunately, reports from multiple sources indicate that guidelines are often not followed, and that acute care in emergency departments and on acute medical wards is suboptimal. It is important to understand what leads to this breakdown in health care, and to identify evidence-based interventions which could be implemented to improve care. This review focuses on recently published articles as well as information about on-going clinical trials.Aspects of care which could potentially make a difference to patient experience include availability and accessibility of individual care plans agreed between patient and treating specialist, innovative means of delivering initial opioids to reduce time to first analgesia, and availability of a specialist unit away from the ED, where expert care can be delivered in a more compassionate environment. The current evidence of improved outcomes and health economic advantage with these interventions is inadequate, and this is hampering their implementation into health care systems.

Recent advancements in gene editing illuminate new potential therapeutic approaches for Sickle Cell Disease (SCD), a debilitating monogenic disorder caused by a point mutation in the β-globin gene. Despite the availability of several FDA-approved medications for symptomatic relief, allogeneic hematopoietic stem cell transplantation (HSCT) remains the sole curative option, underscoring a persistent need for novel treatments. This review delves into the growing field of gene editing, particularly the extensive research focused on curing haemoglobinopathies like SCD. We examine the use of techniques such as CRISPR-Cas9 and homology-directed repair, base editing, and prime editing to either correct the pathogenic variant into a non-pathogenic or wild-type one or augment fetal haemoglobin (HbF) production. The article elucidates ways to optimize these tools for efficacious gene editing with minimal off-target effects and offers insights into their effective delivery into cells. Furthermore, we explore clinical trials involving alternative SCD treatment strategies, such as LentiGlobin therapy and autologous HSCT, distilling the current findings. This review consolidates vital information for the clinical translation of gene editing for SCD, providing strategic insights for investigators eager to further the development of gene editing for SCD.