bims-sicedi Biomed News
on Sickle cell disease
Issue of 2025–01–26
ten papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo
  1. A review on disease modifying pharmacologic therapies for sickle cell disease.
  2. Reply to Holbert and Fraidenburg: Not to Be Forgotten, Pulmonary Vascular Effects of Nonmyeloablative Hematopoietic Cell Transplant for Sickle Cell Disease.
  3. Sickle Cell Anemia and Inflammation: A Review of Stones and Landmarks Paving the Road in the Last 25 Years.
  4. Not to Be Forgotten, Pulmonary Vascular Effects of Nonmyeloablative Hematopoietic Cell Transplant for Sickle Cell Disease.
  5. Musculoskeletal complications in sickle cell disease: Pathophysiology, diagnosis and management.
  6. Impact of Red Cell Exchange Transfusion on Inflammatory Markers in Sickle Cell Disease.
  7. Sickle Cell Anemia Treatment With Hydroxyurea in Low-Resource Settings: Challenges and Opportunities for Global North-South Collaboration.
  8. Pricey sickle cell gene therapies primed for change.
  9. Transcriptomic atlas reveals organ-specific disease tolerance in sickle cell mice.
  10. Genetic Modulators of Diversity in the Biological Expression of Sickle Cell Anemia in Patients from Democratic Republic of Congo: Role of βs-globin Haplotypes.
  1. Ann Hematol. 2025 Jan 20.
    A review on disease modifying pharmacologic therapies for sickle cell disease.
    Himil Mahadevia, Ben Ponvilawan, Ujjwal Madan, Parth Sharma, Hana Qasim, Anuj Shrestha.
      Sickle cell disease (SCD) is an inherited hematologic disease caused by sickle hemoglobin as the predominant RBC hemoglobin or by sickle hemoglobin in combination with other abnormal β-hemoglobin variants like HbC, HbD and others. Sickling of erythrocytes under deoxygenated conditions is the basis of inflammatory and thrombotic cascades which result in multiple serious complications, leading to early morbidity and mortality. While HLA-matched allogeneic bone marrow transplantation is potentially curative, it has considerable limitations due to potential severe toxicities. Despite slow progress towards novel therapeutic strategies for SCD and hydroxyurea being the sole medication that is shown to reduce vaso-occlusive events and mortality for almost 20 years, several pharmacological agents targeting different mechanisms have been examined in clinical trials and recently US- US-FDA-approved, including L-glutamine and crizanlizumab. Voxelotor was previously US-FDA-approved but has been voluntarily withdrawn from the market as the overall benefit did not outweigh the risks. Gene therapies based on CRISPR-Cas9 and lentiviral vectors have been very recently approved. However, excessive costs are a barrier to widespread use. Nonetheless, there is still a large area of unmet needs for patients with SCD, and further research towards better care is warranted.
    Keywords:  Crizanlizumab; Hydroxyurea; L-glutamine; Pharmacologic therapy; Sickle cell disease; Voxelotor
    DOI:  https://doi.org/10.1007/s00277-025-06216-1
  2. Ann Am Thorac Soc. 2025 Jan 21.
    Reply to Holbert and Fraidenburg: Not to Be Forgotten, Pulmonary Vascular Effects of Nonmyeloablative Hematopoietic Cell Transplant for Sickle Cell Disease.
    A Parker Ruhl, Emily M Limerick, Amisha V Barochia, Courtney D Fitzhugh, Matthew M Hsieh.
      
    DOI:  https://doi.org/10.1513/AnnalsATS.202412-1253LE
  3. Hematol Rep. 2025 Jan 10. pii: 2. [Epub ahead of print]17(1):
    Sickle Cell Anemia and Inflammation: A Review of Stones and Landmarks Paving the Road in the Last 25 Years.
    Jessica Dorneles, Amanda de Menezes Mayer, José Artur Bogo Chies.
      A quarter of a century ago, sickle cell disease (SCD) was mainly viewed as a typical genetic disease inherited as a classical Mendelian trait. Therefore, the main focus concerning SCD was on diagnosis, meaning, genotyping, and identification of homozygous and heterozygous individuals carrying the relevant HbS mutant allele. Nowadays, it is well established that sickle cell disease is indeed the result of homozygosis for the HbS variant, although this single feature is not capable of explaining the highly diverse clinical presentation of SCD. In fact, an important feature of SCD is the chronic inflammation that accompanies the sickling of erythrocytes. In this manuscript, we will revisit the early evidence of inflammation in SCD and review what was uncovered during the last 25 years. Here, we describe Sickle cell anemia as a major participant in the history of science. In fact, SCD was the first genetic disease where the causal mutation was identified and is also the first disease for which treatment through genome editing was approved, making this disease a landmark in the road of molecular biology.
    Keywords:  adhesion molecules; inflammation; mannose-binding lectin; sickle cell anemia; vaso-occlusion
    DOI:  https://doi.org/10.3390/hematolrep17010002
  4. Ann Am Thorac Soc. 2025 Jan 21.
    Not to Be Forgotten, Pulmonary Vascular Effects of Nonmyeloablative Hematopoietic Cell Transplant for Sickle Cell Disease.
    Kelsey Holbert, Dustin R Fraidenburg.
      
    DOI:  https://doi.org/10.1513/AnnalsATS.202411-1188LE
  5. Best Pract Res Clin Rheumatol. 2025 Jan 16. pii: S1521-6942(25)00001-4. [Epub ahead of print] 102033
    Musculoskeletal complications in sickle cell disease: Pathophysiology, diagnosis and management.
    Parul Gupta, Suyesh Shrivastava, Ravindra Kumar.
      Sickle cell disease (SCD) is a mono-genic disorder causing chronic hemolysis, anemia, and vaso-occlusion, leading to musculoskeletal complications such as osteonecrosis, osteoporosis, and bone fractures affecting 50-70% SCD patients. These complications result from a complex interplay of genetic and physiological factors, including abnormal hemoglobin production, chronic inflammation, and oxidative stress. This review discusses the pathophysiology, pre-clinical symptoms, and clinical manifestations of musculoskeletal complications in SCD, as well as current treatment options, including pharmacological interventions, surgical procedures, and bone marrow transplantation. Early detection of pre-clinical symptoms is crucial to prevent progression. Pharmacological interventions (analgesics, anti-inflammatory agents, bone-modifying agents and hydroxyurea), surgical interventions (core decompression, bone grafting, joint replacement and osteotomy) and supportive measures enhance mobility, strength and well-being. A multidisciplinary approach is essential for optimal care, and early diagnosis and management are crucial to prevent long-term damage and improve outcomes. Future research directions include targeted therapies, biomarker investigation and infrastructure development to improve outcomes for SCD individuals with musculoskeletal complications.
    Keywords:  Musculoskeletal; Osteonecrosis; Osteoporosis; Sickle cell disease; Vaso-occlusion
    DOI:  https://doi.org/10.1016/j.berh.2025.102033
  6. Mediterr J Hematol Infect Dis. 2025 ;17(1): e2025011
    Impact of Red Cell Exchange Transfusion on Inflammatory Markers in Sickle Cell Disease.
    Adriana Costa, Inês Filipa Mendes, Joana Lage, Marta Moniz, Catarina Amorim, Pedro Nunes, Helena Almeida, Ana Ventura, Teresa Ferreira, Carlos Escobar.
       Background: Red Blood Cell Exchange (RBCX) is a common treatment for pediatric sickle cell disease (SCD). Since inflammation with elevated proinflammatory cytokines plays a crucial role in SCD, this study hypothesized that RBCX might lower these cytokines and aimed to assess the impact of this technique on these markers.
    Methods: Prospective and observational study of pediatric SCD patients (HbSS genotype) enrolled in a chronic RBCX program at a Portuguese Hospital from October 2022 to August 2024. Blood samples were collected before and after RBCX to assess hematological and inflammatory markers. Data were analyzed using SPSSv25 ® (Significance level p < 0.05); Informed consents were obtained.
    Results: Thirty-one children (median age 10 years) were studied: 14 were treatment-naïve, and 17 were previously in a chronic RBCX program. The primary indication for starting the program was cerebrovascular disease prevention (81%). Analysis of 286 RBCXs showed no major adverse events or disease-related hospitalizations. Hemoglobin levels increased by 1.5g/dL post-RBCX; HbS, leukocytes, IL-1, and CRP decreased by 69%, 20%, 21%, and 13%, respectively. Other markers showed no significant changes. IL-1, ferritin, and procalcitonin showed high levels before RBCX; IL-6 showed high levels post-RBCX. Considering only naïve patients, they had higher pre-RBCX IL-1 levels than those with prior RBCX (difference of 22.6 pg/mL); IL-6 increased by 17.3% and IL-1 decreased by 23.9% post-RBCX (p < 0.001).
    Conclusions: RBCX safely reduces HbS, leukocytes, and IL-1 levels, suggesting a modulatory effect on inflammation in SCD patients. Further research is needed to explore cytokine mechanisms in SCD.
    Keywords:  Inflammatory cytokines; Red blood cell exchange; Sickle cell anemia
    DOI:  https://doi.org/10.4084/MJHID.2025.011
  7. Int J Public Health. 2024 ;69 1606984
    Sickle Cell Anemia Treatment With Hydroxyurea in Low-Resource Settings: Challenges and Opportunities for Global North-South Collaboration.
    Teresa S Latham.
      
    Keywords:  capacity building; global health; hydroxyurea; pediatrics; sickle cell anemia
    DOI:  https://doi.org/10.3389/ijph.2024.1606984
  8. Nat Biotechnol. 2025 Jan;43(1): 8
    Pricey sickle cell gene therapies primed for change.
      
    DOI:  https://doi.org/10.1038/s41587-024-02542-3
  9. Blood Adv. 2025 Jan 22. pii: bloodadvances.2024013435. [Epub ahead of print]
    Transcriptomic atlas reveals organ-specific disease tolerance in sickle cell mice.
    Anne Grunenwald, Julie Peliconi, Julien Lavergne, Margot Revel, Elodie Voilin, Tania Robe-Rybkine, Gilles Crambert, Jordan D Dimitrov, Olivier Blanc-Brude, Lubka T Roumenina.
      Sickle cell disease (SCD) is the most common genetic disease in the world and a societal challenge. SCD is characterized by multi-organ injury related to intravascular hemolysis. To understand tissue-specific responses to intravascular hemolysis and exposure to heme, we present a transcriptomic atlas in the primary target organs of HbSS vs HbAA transgenic SCD mice. We explored the transcriptomes of liver, kidney, heart, lung and bone marrow from HbAA and HbSS Townes littermates at resting state and their changes after injection of heme, assessed by RNA sequencing. Inflammation and myeloid cell signatures were omnipresent in resting HbSS organs, liver being the most affected. The injection of heme triggered a robust inflammatory response in HbAA mice. Signatures of exposure to heme in HbAA mice were downstream of TLR4 (sensor of LPS but also of heme), IL1b, IL6 and IFNg, similarly to HbSS mice at rest. Nevertheless, HbSS mice were strikingly unresponsive to heme administration, irrespective of the organ. This tolerance was driven by upregulation of the heme-detoxifying enzyme HO-1 and was abrogated by its specific inhibition. Therefore, HbSS mice develop robust protective mechanisms, which may explain how they and SCD patients survive bouts of severe hemolysis.
    DOI:  https://doi.org/10.1182/bloodadvances.2024013435
  10. Mediterr J Hematol Infect Dis. 2025 ;17(1): e2025001
    Genetic Modulators of Diversity in the Biological Expression of Sickle Cell Anemia in Patients from Democratic Republic of Congo: Role of βs-globin Haplotypes.
    Mamy Ngole, Gloire Mbayabo, Paul Lumbala, Valerie Race, Nono Mvuama, Stephanie Deman, Erika Souche, Prosper Tshilobo Lukusa, Chris Van Geet, Koenraad Devriendt, Gert Matthijs, Aimé Lumaka, Isabelle Cleynen.
      
    Keywords:  DR Congo; HbF; SCA haplotypes; Sickle cell anemia; Single nucleotide polymorphisms
    DOI:  https://doi.org/10.4084/MJHID.2025.001
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