bims-sicedi Biomed News
on Sickle cell disease
Issue of 2025–08–31
nine papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo
  1. Gene Therapy for HbSC Disease and other Compound Heterozygous Sickle Hemoglobinopathies: A Time for Inclusion.
  2. Hemoglobin and High-Density Lipoprotein as Biomarker of Left Atrial Dilatation in Sickle Cell Disease.
  3. Extracranial internal carotid artery and cerebral infarction in paediatric sickle cell patients.
  4. Oxygen-tunable endothelialized microvascular chip to assess hypoxia-reperfusion in sickle cell disease.
  5. A prime editing strategy to rewrite the γ-globin promoters and reactivate fetal hemoglobin for sickle cell disease.
  6. Alloimmunization and consequential delayed hemolytic transfusion reactions in sickle cell disease patients: A case series.
  7. Nalbuphine as a Potential Alternative to Morphine in Sickle Cell Disease Patients with Vaso-occlusive Crisis: A Retrospective Cohort Study.
  8. Updating the Brazilian clinical practice guidelines for sickle cell disease: Recommendations and development process.
  9. The efficacy of oral L-arginine therapy for the treatment of vaso-occlusive pain episodes in children with sickle cell disease.
  1. Blood. 2025 Aug 20. pii: blood.2025029964. [Epub ahead of print]
    Gene Therapy for HbSC Disease and other Compound Heterozygous Sickle Hemoglobinopathies: A Time for Inclusion.
    Andrew Wilks, Martin H Steinberg, Haydar Frangoul.
      Two gene therapy products have been FDA approved for sickle cell disease. Nearly all patients in the clinical trials that led to approval were either sickle hemoglobin gene homozygotes (sickle cell anemia) or had HbS-β0 thalassemia. HbSC disease, caused by compound heterozygosity for HbS and HbC genes, is the second most common genotype of sickle cell disease. Gene therapy has not been tested in HbSC disease patients who are severely symptomatic. We discuss the pathophysiology and clinical features of HbSC disease, and how gene therapy is likely to provide a curative option for some individuals. We also discuss the mechanism through which HbF and HbF-like HbA (HbAT87Q) might mitigate adverse clinical outcomes and end-organ damage in HbSC disease and other compound heterozygous sickle hemoglobinopathies.
    DOI:  https://doi.org/10.1182/blood.2025029964
  2. EJHaem. 2025 Aug;6(4): e70135
    Hemoglobin and High-Density Lipoprotein as Biomarker of Left Atrial Dilatation in Sickle Cell Disease.
    Guillaume Feugray, Maximilien Grall, Baptiste Gillardin, Julie Burdeau, Nicolas Ozanne, Cécile Dumesnil, Charles Fauvel, Paul Billoir.
      Sickle cell disease (SCD) is associated with cardiac remodeling, particularly left atrial dilatation, which may predict adverse cardiovascular outcomes. This study assessed cardiac abnormalities using echocardiography in 59 adult SCD patients and explored biomarkers predictive of left atrial remodeling. Left atrial dilatation was found in 61% of patients and significantly associated with hemoglobin, hemoglobin S, HDL-C, and the atherogenic index of plasma. An algorithm combining hemoglobin ≤ 9.7 g/dL and HDL-C ≤ 50 mg/dL showed high-diagnostic performance. These findings support biomarker-based screening as a useful tool in resource-limited settings for early detection of cardiac complications in SCD. Trial Registration: ClinicalTrials.gov identifier: NCT05376046.
    Keywords:  hemolysis; high‐density lipoprotein; left atrial remodeling; sickle cell disease
    DOI:  https://doi.org/10.1002/jha2.70135
  3. Haematologica. 2025 Aug 21.
    Extracranial internal carotid artery and cerebral infarction in paediatric sickle cell patients.
    Bart J Biemond.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2025.288350
  4. Lab Chip. 2025 Aug 20.
    Oxygen-tunable endothelialized microvascular chip to assess hypoxia-reperfusion in sickle cell disease.
    Samantha R Schad, Joan D Beckman, Wilbur A Lam, David K Wood.
      A better understanding of hypoxia reperfusion (H/R) injury is needed to gain deeper insight into the mechanisms driving sickle cell disease (SCD) pathophysiology. Existing in vivo and in vitro models have yet to fully explain H/R, which is typically associated with harmful inflammatory processes but has also been linked to a protective effect ameliorating subsequent severe vaso-occlusion. To address this need, we developed a novel microfluidic platform that includes three-dimensional endothelial-lined microchannels within an oxygen-tunable environment. These features enable simulation of H/R, red blood cell (RBC) sickling, and vaso-occlusion on-chip. The endothelial network cultured on-chip is physiologically relevant and expresses crucial microvascular features such as 3D lumen structure and expression of functional endothelial markers. We utilized this platform to perform an occlusion assay, evaluating the effects of hypoxic preconditioning on RBC-endothelial interactions contributing to occlusion. Our results demonstrate that both sustained mild hypoxia and cyclic hypoxia endothelial treatment reduce the likelihood of SCD occlusion on-chip. Specifically, average vaso-occlusion rates of 8.89% and 11.78% were observed among endothelialized devices preconditioned to cyclic and sustained hypoxia, respectively, compared to 57.93% and 55.05% for the control groups. Additionally, we leveraged RNA sequencing to identify differential regulation of specific genes contributing to this protective outcome. Of note, hypoxia preconditioning resulted in significant modulation of CYBB, RELN, and SERPINA1. These results offer a better understanding of the mechanistic changes affecting the endothelium during H/R and also offer potential targets for further exploration and therapeutic intervention in SCD.
    DOI:  https://doi.org/10.1039/d5lc00211g
  5. Blood. 2025 Aug 26. pii: blood.2024028166. [Epub ahead of print]
    A prime editing strategy to rewrite the γ-globin promoters and reactivate fetal hemoglobin for sickle cell disease.
    Anne Chalumeau, Maria Bou Dames, Letizia Fontana, Simone Amistadi, Panagiotis Antoniou, Priyanka Loganathan, Margaux Mombled, Guillaume Corre, Martin Peterka, Mario Amendola, Carine Giovannangeli, Marcello Maresca, Annarita Miccio, Mégane Brusson.
      Fetal hemoglobin (HbF) reactivation is a promising therapy for β-hemoglobinopathies. We developed a prime-editing strategy that introduces multiple mutations in the fetal γ-globin promoters that are expected to increase their activity. We tested multiple targets and optimized a variety of parameters to achieve ~50% of precise edits in a hematopoietic cell line, with minimal off-targets effects. This work improved our understanding of the complex DNA repair mechanisms involved in prime editing. We tested this strategy in patients' hematopoietic stem/progenitor cells (HSPCs). Although the editing efficiency was variable amongst donors, erythroid clones carrying multiple mutations express a significantly higher γ-globin level compared to cells carrying individual mutations, confirming the potential therapeutic benefit of our combined strategy for patients with β-hemoglobinopathies.
    DOI:  https://doi.org/10.1182/blood.2024028166
  6. Asian J Transfus Sci. 2025 Jan-Jun;19(1):19(1): 167-172
    Alloimmunization and consequential delayed hemolytic transfusion reactions in sickle cell disease patients: A case series.
    Tahsim Anwar, Satya Prakash, Ansuman Sahu, Somnath Mukherjee, Debasish Mishra.
      Alloimmunization is a significant complication of blood transfusion, especially in sickle cell patients, and may lead to a delayed hemolytic transfusion reaction (DHTR). DHTR is defined as evident hemolysis and a positive direct antiglobulin test (DAT) 24 h to 28 days posttransfusion with either a positive eluate or a newly identified alloantibody in the plasma. Hyperhemolysis syndrome (HS) is a fatal form of DHTR in which the posttransfusion hemoglobin (Hb) level is less than the pretransfusion Hb level. In this case series, we have reported three cases of alloimmunized sickle cell disease patients with clinically significant DHTR. The second case is typical of HS. All three cases were DAT positive, alloimmunized with multiple alloantibodies, and had substantial hemolysis posttransfusion. In this series, we have provided an algorithmic approach to resolve such complex immunohematological problems and have highlighted some of the limitations of serology methods. High-dose corticosteroid and intravenous immunoglobulin prove to be an effective treatment for DHTR.
    Keywords:  Alloimmunization; delayed hemolytic transfusion reaction; direct antiglobulin test; hyperhemolysis syndrome; sickle cell disease
    DOI:  https://doi.org/10.4103/ajts.ajts_191_23
  7. Saudi J Med Med Sci. 2025 Jul-Sep;13(3):13(3): 181-188
    Nalbuphine as a Potential Alternative to Morphine in Sickle Cell Disease Patients with Vaso-occlusive Crisis: A Retrospective Cohort Study.
    Mohannad Alghamdi, Mohamed Almulhim, Qasem Almulihi, Yousef A Alhamaid, Mohammad Assiri, Abdullah Alzahid, Basmah Al Ghanim, Lama Albaish, Lama Alkhunaizi, Shahad Alali, Layan Alshehri.
       Background: The use of morphine in managing vaso-occlusive crisis (VOC) in patients with sickle cell disease (SCD) can result in significant side effects. Nalbuphine, a mixed agonist-antagonist opioid, may offer an alternative with fewer complications.
    Objective: To compare the efficacy and safety of nalbuphine and morphine in pain management among adult SCD patients presenting with VOC.
    Methods: This retrospective study included adult patients with SCD treated at King Fahad Hospital, Hofuf, Saudi Arabia, between 2019 and 2023. Patients were classified into two groups (receiving morphine and nalbuphine). Pain levels were assessed using the Visual Analog Scale (VAS) at baseline, 1-h, 6-h, and 24-h post-administration. Additional outcomes included the need for rescue medication and discharge rates from the emergency department.
    Results: A total of 234 patients were included (morphine: 120; nalbuphine: 114). The mean age of the cohort was 30.5 ± 8.7 years, and 63.8% were female. Baseline laboratory data indicated mean hemoglobin of 8.5 g/dL and elevated lactate dehydrogenase (576.9 U/L). At 6 h, 10% and 20% of patients on morphine and nalbuphine, respectively, reported no pain (P = 0.013). At 24 h, 30% and 40% of patients on nalbuphine and 15% and 25% on morphine experienced no pain and mild pain, respectively (P = 0.00002). Nalbuphine patients required less rescue medication (41% vs. 59%, P = 0.009) and had higher discharge rates from the emergency department (70% vs. 46%, P = 0.0003). No significant difference was found in the incidence of acute chest syndrome or ICU admissions between the two groups.
    Conclusion: Nalbuphine can be a potential alternative for vaso-occlusive crisis pain management in sickle cell disease patients, as it demonstrated superior efficacy compared with morphine, especially at later time points, with reduced need for rescue medication and earlier discharge.
    Keywords:  Morphine; nalbuphine; opioid therapy; pain management; sickle cell disease; vaso-occlusive crisis
    DOI:  https://doi.org/10.4103/sjmms.sjmms_601_24
  8. Hematol Transfus Cell Ther. 2025 Aug 23. pii: S2531-1379(25)00232-9. [Epub ahead of print]47(4): 103964
    Updating the Brazilian clinical practice guidelines for sickle cell disease: Recommendations and development process.
    Ludmila Peres Gargano, Mariana Millan Fachi, Layssa Andrade Oliveira, Clarisse Lobo, Katharina Nelly Tobos Melnikoff, Selma Soriano, Marta da Cunha Lobo Souto Maior, Meline Rossetto Kron-Rodrigues, Dalila Fernandes Gomes, Haliton Alves Oliveira Junior, Rosa Camila Lucchetta.
       BACKGROUND: Sickle cell disease is a hereditary blood disorder that significantly impacts morbidity and mortality, requiring comprehensive care. In Brazil, its management in the National Health Service follows the Brazilian Clinical Practice Guidelines, based on evidence and expert consensus. Periodic updates ensure alignment with new scientific findings.
    OBJECTIVES: This study describes the methodology for updating the clinical guidelines for sickle cell disease and provides an overview of recommendations for diagnosis, treatment and monitoring, emphasizing the evidence and health technology assessments for prioritized technologies.
    METHODS: The update followed the technical guide of the Brazilian Ministry of Health, and the Gradings of Recommendation, Assessment, Development and Evaluation (GRADE) approach. All the recommendations were assessed by the National Committee for Health Technology Incorporation (Conitec). The clinical guidelines panel included health technology assessment researchers, clinical experts, and policymakers. Systematic reviews assessed new evidence with stakeholder contributions being incorporated through public consultation. Cost-effectiveness analysis was applied to support new technology coverage or changes.
    RESULTS: The updated clinical guidelines provide structured recommendations for screening, diagnosis, prophylaxis, vaccination, and treatment, covering pharmacological and non-pharmacological approaches. It emphasizes patient and caregiver education to promote early recognition of complications. Expected benefits include fewer pain crises, fewer hospitalizations and transfusions, and improved fetal hemoglobin level, quality of life and survival rates. Key updates include listing epoetin alfa and 100 mg hydroxyurea tablets, expanding hydroxyurea eligibility criteria and revising monitoring protocols.
    CONCLUSION: The updated clinical practice guidelines standardize sickle cell disease care in the Brazilian NHS aligned with current evidence. Dissemination and integration aim to enhance healthcare delivery, while future assessments should optimize real-world implementation.
    Keywords:  Health technology assessment; Practice guidelines; Public health; Sickle cell anemial
    DOI:  https://doi.org/10.1016/j.htct.2025.103964
  9. Pediatr Hematol Oncol. 2025 Aug 27. 1-13
    The efficacy of oral L-arginine therapy for the treatment of vaso-occlusive pain episodes in children with sickle cell disease.
    Aya Mohamed Abd Elglil, Mohamed Ramadan El-Shanshory, Hamed Mohamed Elsharkawy, Walaa Arafa Keshk, Nahed M Hablas, Lamia M Morad.
      Pain is the clinical hallmark of sickle cell disease (SCD), with painful Vaso-occlusive episodes (VOEs) being the common medical emergencies associated with an increased mortality rate. The current study aimed to evaluate the efficacy of L-arginine as an adjuvant therapy for children with SCD and VOE, as well as its effect on Tricuspid Regurgitant Jet Velocity (TRJV) during VOE. The primary outcome was to evaluate the efficacy of L-arginine on pain intensity. This double-blind, randomized, controlled, and parallel prospective study was carried out on 40 SCD children who presented with VOE and met the inclusion criteria. The mean ± SD of age was 8.8 ± 3.2 years, and 62.5% were males. They were randomized into two groups; Group 1 included 20 patients who received L-Arginine (100 mg/kg/dose three times/day for 15 doses or until their discharge) plus standard therapy. Group 2 consisted of 20 patients who received a placebo in addition to standard therapy. Total analgesic use, daily pain score, time to crisis resolution, and length of hospital stay were recorded. Routine laboratory investigations, serum L-Arginine, asymmetric dimethyl-arginine (ADMA) levels and the Arginine/ADMA ratio were assessed. Moreover, Echocardiography was performed to assess TRJV. All these parameters were assessed at baseline (during painful crisis), at discharge, and during the clinically asymptomatic state. As regards the age, sex, consanguinity, or family history there were no statistically significant difference between all of the studied groups. L-arginine therapy significantly decreased pain score at the 3rd day of admission(p-value 0.036), total analgesic use (p-value <0.001), time to crisis resolution (p-value 0.011), length of hospital stays (p-value 0.016), and TRJV (p-value < 0.001). Additionally, serum L-arginine level and Arginine/ADMA ratio (p-value <0.001) were increased upon arginine treatment. Additionally, statistically significant differences in the serum L-arginine level, serum ADMA level, Arginine/ADMA ratio, and TRJV were reported during painful crisis compared to the asymptomatic state. L-arginine Supplementation improved painful VOE symptoms in SCD children and decreased TRJV in those children. Oral arginine could be a promising adjuvant therapy for SCD-VOE management.
    Keywords:  ADMA; L-arginine; sickle cell disease (SCD); tricuspid regurgitant jet velocity (TRJV); vaso-occlusive episodes (VOE)
    DOI:  https://doi.org/10.1080/08880018.2025.2549365
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