bims-sicedi 2025-11-02 papers

Br J Haematol. 2025 Oct;207 Suppl 1 S5-S135

20th Annual Sickle Cell & Thalassaemia Conference, 1-4 October 2025, London.

Blood Adv. 2025 Oct 28. pii: bloodadvances.2025017321. [Epub ahead of print]

Comparative Analysis of CRISPR-Cas9, lentiviral transduction, and base editing for sickle cell disease in a murine model.

Henna Butt, Shruti Sathish, Evan London, Anh Le, Quan Li, Bjorg Gudmundsdottir, Duck-Yeon Lee, Emma V Burke, Bradley P Yates, David R Liu, Matthew M Hsieh, Alexis Leonard, William A Eaton, Naoya Uchida, Francis J Pierciey, Gregory A Newby, John F Tisdale, Selami Demirci.

Sickle Cell Disease (SCD) is a red blood cell disorder caused by a mutation in the β-globin gene, leading to sickle hemoglobin (HbS) polymerization under low oxygen conditions. CRISPR-Cas9 editing and lentiviral transduction have shown promising clinical outcomes, but it remains unclear which approach is superior. Alternatively, new editing tools such as base editing may also be promising and reduce risks of genotoxicity. To compare these approaches, we studied them in an immunocompromised mouse model. We optimized ex vivo conditions in CD34+ hematopoietic stem and progenitor cells (HSPCs) and infused edited SCD HSPCs into busulfan-conditioned NBSGW mice. Ex vivo analysis confirmed successful editing and transduction. At 16 weeks, bone marrow (BM) analysis showed similar human CD45+ cell engraftment across all groups (75-90%). In the competitive transplantation group, there was a lower amount of BCL11A enhancer editing compared to base editing and lentiviral transduction. A secondary transplantation model yielded similar results. An anti-sickling assay showed significantly higher RBC sickling reduction in the base editing, transduction, and competitive transplantation groups compared to CRISPR-Cas9. In conclusion, while all methods showed therapeutic potential, base editing and lentiviral transduction provided superior outcomes over CRISPR-Cas9-mediated editing in a competitive murine transplantation model.

DOI: https://doi.org/10.1182/bloodadvances.2025017321

Br J Haematol. 2025 Oct 28.

Cerebral blood flow trajectories in paediatric sickle cell anaemia by age, region, and treatment associations.

Ping Zou Stinnett, Robert J Ogg, Kathleen Helton, Winfred Wang, Andrew M Heitzer, Zachary Abramson, Yimei Li, Tushar Patni, Paul VanGilder, Akshay Sharma, Ranganatha Sitaram.

Opposite to the age trend in healthy children, cerebral blood flow increases with age in children with sickle cell anaemia. Early treatment with hydroxyurea (hydroxycarbamide) may help slow this abnormal trend and protect brain functions.

Keywords: cerebral blood flow; hydroxyurea (hydroxycarbamide); paediatric; sickle cell anaemia

DOI: https://doi.org/10.1111/bjh.70224

Res Pract Thromb Haemost. 2025 Oct;9(7): 103193

Emerging pathways in thromboinflammation of sickle cell disease: novel findings in disease pathogenesis.

Nirupama Ramadas, Erica Sparkenbaugh.

Sickle cell disease (SCD) is increasingly recognized as a chronic thromboinflammatory disorder, marked by persistent intravascular hemolysis, sustained endothelial activation, and multicellular aggregate formation. Free hemoglobin and heme act as damage-associated molecular patterns, activating Toll-like receptor 4 and promoting inflammatory and procoagulant responses in endothelial cells, monocytes, and neutrophils. Hyperreactive platelets, sickled red blood cells, and activated leukocytes interact with the endothelium to propagate vascular occlusion and thrombin generation. This persistent thromboinflammatory state targets low-flow microvascular beds in the bone marrow, lung, kidney, spleen, and brain, culminating in progressive end-organ dysfunction. In this article, we review the cellular and molecular drivers of thromboinflammation in SCD, highlighting how sustained vascular injury leads to deep vein thrombosis, stroke, nephropathy, and cardiopulmonary complications. Understanding these mechanisms is essential for developing targeted strategies to disrupt the thromboinflammatory cycle and prevent irreversible organ damage in SCD.

Keywords: anemia; hemoglobinopathy; neutrophils; platelets; sickle cell disease; thromboinflammation

DOI: https://doi.org/10.1016/j.rpth.2025.103193

Br J Haematol. 2025 Oct 28.

Bone marrow necrosis and fat embolism in critically ill patients with acute complications of sickle cell disease: A retrospective cohort study.

Ségolène Gendreau, Jérôme Cecchini, Keyvan Razazi, Caroline Ratnam, Anoosha Habibi, Armand Mekontso Dessap.

Keywords: bone marrow necrosis; sickle cell disease; thrombocytopenia

DOI: https://doi.org/10.1111/bjh.70165