bims-sicedi 2026-01-18 papers

Front Stroke. 2024 ;3 1368576

Sickle cell anemia and early stroke detection and prevention in Nigeria.

Kudirat Abdulkareem Ahmed, Halima Bello-Manga, Lori C Jordan.

Sickle cell disease (SCD) is the most common hereditary blood disorder worldwide, and sickle cell anemia (SCA), the homozygous state of SCD, is the most common and severe variant of the disease. Nigeria has the highest burden of SCA in the world. Hemolysis and vaso-occlusion can lead to a wide range of complications, including stroke which is one of the most devastating manifestations of SCA with significant morbidity and mortality. SCA remains the leading cause of stroke in black children. Without any intervention, strokes occur in approximately 11% of children with SCA before their 20th birthday, with the greatest risk in very young children between 2 and 5 years of age. In resource-constrained countries, where the burden of SCA is highest, stroke is underreported, hence the need to develop strategies for stroke prevention and early detection. Improving awareness among healthcare providers and the community can significantly reduce stroke rates and improve stroke detection. The goal of this manuscript is to discuss the progress that has been made in stroke prevention and detection in children with SCA in Nigeria and outline current challenges and future goals. We believe that our experience will be valuable not only in Nigeria which has the highest burden of SCA globally, but also in other low- and middle-income countries.

Keywords: hydroxyurea; low- middle income setting; sickle cell anemia; stroke; stroke prevention; transcranial doppler

DOI: https://doi.org/10.3389/fstro.2024.1368576

Hematol Transfus Cell Ther. 2026 Jan 10. pii: S2531-1379(25)02515-5. [Epub ahead of print]48(1): 106251

Drug development for sickle cell disease: repeated setbacks, yet there remains an optimistic outlook for future breakthroughs.

Rodolfo Cançado, Fernando Ferreira Costa.

DOI: https://doi.org/10.1016/j.htct.2025.106251

Hemasphere. 2026 Jan;10(1): e70278

MeMAGEN: A Phase IIa/IIb open-label trial of memantine testing safety and tolerability in sickle cell patients.

Ariel Koren, Carina Levin, Leonid Livshits, Fabio Valeri, Sari Peretz, Sivan Raz, Anna Yu Bogdanova, Max Gassmann.

Administration of memantine, an antagonist of the N-methyl- d-aspartate receptor, prevents Ca2+ overload and dehydration of red blood cells (RBCs) in patients with sickle cell disease (SCD). The objectives of the 1-year dose-escalation Phase IIa/IIb Memantine trial (MeMAGEN - NCT03247218) with 17 SCD patients who were under stable hydroxycarbamide therapy were to test the drug's safety and tolerability. Daily memantine doses ranged from 5 to 15 mg for children/adolescents and from 5 to 20 mg for adults. Clinical and laboratory analysis showed that memantine was well tolerated. In children, a decrease in days spent in the hospital was observed. Safety was confirmed by laboratory tests, which were not, or were only minimally, altered during memantine therapy. In a subgroup of six patients whose RBCs presented with elevated K+ leakage before treatment, memantine therapy at its lowest dosage reduced this K+ loss and increased hemoglobin concentration. This study shows that memantine is safe and well tolerated by SCD patients, including children. Memantine has the potential to become a supportive and low-cost therapy in conjunction with hydroxycarbamide.

DOI: https://doi.org/10.1002/hem3.70278

Nat Commun. 2026 Jan 14.

CD39 polymorphism enables lung thrombosis in sickle cell disease.

Sickle cell disease (SCD) is the most common monogenic-hemolytic disorder affecting people of African ancestry. Adenosine diphosphate (ADP) released following intravascular hemolysis activates platelets by stimulating purinergic receptors to promote thrombosis. Despite brisk intravascular hemolysis, which releases high levels of ADP into plasma, and evidence of platelet and hemostatic activation, it remains elusive why only a subset of SCD patients develop lung thrombosis. Using real-time in vivo lung microscopy, we report a surprising finding that humanized SCD mice are protected from ADP-induced lung thrombosis, which is secondary to the degradation of ADP by CD39 present in circulating extracellular vesicles released by the lung endothelium. ADP-induced platelet aggregation is also impaired in the blood of SCD patients with elevated levels of CD39+ extracellular vesicles. CD39 polymorphism rs3176891A→G is associated with the incidence of lung thrombosis in SCD patients but not healthy humans of African ancestry. Remarkably, CD39+ extracellular vesicles are fewer and ADP-induced platelet aggregation is higher in the blood of SCD patients with rs3176891G allele. This study identifies a novel extracellular vesicle-dependent mechanism preventing lung thrombosis in SCD and reveals how CD39 polymorphisms may impair this protection to increase the risk for lung thrombosis in a subset of SCD patients.

DOI: https://doi.org/10.1038/s41467-026-68396-2

Eur J Haematol. 2026 Jan 13.

Whole Blood Transcriptomic Analysis of Sickle Cell Trait.

Mari Johnson, Yanwei Cai, Ana Gabriela Vasconcelos, Peter Orchard, Paul L Auer, Guillaume Lettre, Jia Wen, Nora Franceschini, Charles Kooperberg, Wei Sun, Li Hsu, Laura M Raffield, Alex P Reiner.

Sickle cell trait (SCT) is the heterozygous carrier state for the HBB missense variant which causes sickle cell disease (SCD). SCT has been associated with increased risk of venous thromboembolism and chronic kidney disease as well as alterations in clinical laboratory parameters. To investigate differential gene expression in SCT, we used RNA sequencing of whole blood samples collected from 805 African American female participants (143 SCT; 660 controls) from the Women's Health Initiative Long Life Study (mean age = 76). We identified 226 differentially expressed genes (DEGs) in SCT compared to non-carriers (FDR < 0.05). Enriched pathways included those related to erythropoiesis, hemoglobin synthesis, and proteasomal degradation. Many of the SCT-associated DEGs were previously reported as differentially expressed in blood from individuals with SCD. Among the DEGs associated with SCT, we observed enrichment of upregulated ubiquitin-related genes normally downregulated during the later stages of erythroid differentiation, a pattern previously reported in SCD. Several of the SCT-associated DEGs highlight mechanisms that potentially link hemolysis or erythropoiesis to hypoxic kidney tubular injury. Future investigation of these genes using single cell transcriptomic analysis in relevant tissues may be useful in understanding mechanisms for adverse health outcomes in individuals with SCT.

Keywords: chronic kidney disease; erythropoiesis; sickle cell disease; sickle cell trait; ubiquitination

DOI: https://doi.org/10.1111/ejh.70114

Am J Hematol. 2026 Jan 12.

RBC Alloimmunization Impacts Pediatric Sickle Cell Disease Transplant Outcomes and Transfusion Burden: A STAR Registry Report.

Patients with sickle cell disease (SCD) commonly receive red blood cell (RBC) transfusions and can become RBC alloimmunized. This study was designed to investigate if RBC alloimmunization before hematopoietic cell transplant (HCT) was associated with post-HCT outcomes and transfusion support using the multicenter Sickle cell Transplant Advocacy and Research (STAR) retrospective registry. From a cohort of 229 pediatric patients with SCD who underwent human leukocyte antigen (HLA)-matched related donor HCT with myeloablative or reduced intensity conditioning, 40 patients (17%) were RBC alloimmunized pre-HCT. The RBC alloimmunized group had a significantly higher incidence of grade III-IV acute graft-versus-host disease (GVHD) (15% vs. 3.7%, p = 0.013), which remained significant (OR 4.22, 95% CI, 1.19, 14.3; p = 0.027) when controlling for pre-HCT RBC transfusion burden and conditioning intensity. Graft failure occurred in 10% of RBC alloimmunized patients compared with 2.6% of non-alloimmunized patients, p = 0.052. Patients with RBC alloimmunization had lower 5-year severe GVHD-free, rejection-free survival (69% vs. 88%, p = 0.004), which remained significant when controlling for age. Post-HCT patients received a median 3 RBC units (IQR 2, 6) and 11 platelet transfusions (IQR 7, 19). Pre-HCT RBC alloimmunization was associated with a greater requirement for post-HCT platelet transfusions, but not post-HCT RBC units transfused. We postulate that the observed associations of pre-HCT RBC alloimmunization with severe acute GVHD and post-HCT platelet transfusion burden are due to inherent immunologic characteristics that render patients at increased risk of developing multiple immune-mediated complications.

DOI: https://doi.org/10.1002/ajh.70200

Blood Adv. 2026 Jan 13. pii: bloodadvances.2025018364. [Epub ahead of print]

Initial Low and Moderate Dose of Hydroxyurea Has a Durable Impact on Primary Stroke Prevention in Low-Income Settings.

Shehu U Abdullahi, Najibah Galadanci, Halima Bello-Manga, Umma A Ibrahim, Binta Wudil Jibir, Abdulkadir Halifa Yusuf, Jamil A Galadanci, Mark J Rodeghier, Michael R DeBaun.

DOI: https://doi.org/10.1182/bloodadvances.2025018364