bims-sicedi Biomed News
on Sickle cell disease
Issue of 2025–01–12
eight papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo
  1. Respiratory manifestations of sickle cell disease in children: a comprehensive review for the pediatrician.
  2. The modern use of hydroxyurea for children with sickle cell anemia.
  3. Missing the mark(ers): circulating endothelial cells and endothelial-derived extracellular vesicles are elevated in sickle cell disease plasma.
  4. Re-energising therapy options in sickle cell disease: the mitapivat phase 2 trial results.
  5. Influence of Weather on Sickle Cell Disease Vaso-Occlusive Episodes and Acute Chest Syndrome: A Nationwide Sample Analysis.
  6. [Extramedullary hematopoiesis, a rare complication of sickle cell disease: A six-case series and literature review].
  7. Major ABO Incompatibility in Non-Myeloablative Hematopoietic Stem Cell Transplant for Sickle Cell Disease-Not an Insurmountable Obstacle.
  8. Lactated Ringer Instead of Normal Saline Solution for Sickle Cell Vaso-Occlusive Episodes.
  1. Expert Rev Respir Med. 2025 Jan 09.
    Respiratory manifestations of sickle cell disease in children: a comprehensive review for the pediatrician.
    Lisa Grigoli, Maria Maiocchi, Laura Venditto, Michele Piazza, Laura Tenero, Giorgio Piacentini, Marco Zaffanello, Giuliana Ferrante.
       INTRODUCTION: Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by the production of sickle hemoglobin, leading to red blood cells sickling and hemolysis in hypoxic conditions. The resulting acute and chronic endothelial inflammation leads to chronic organ damage. Respiratory manifestations in SCD usually start from childhood and represent the leading causes of morbidity and mortality. Nevertheless, they are generally poorly addressed or recognized later in life, often contributing to a more severe course and complications.
    AREAS COVERED: This narrative review aims to outline the significant acute and chronic respiratory manifestations in children with SCD, focusing on prevention and clinical management. Compelling issues that need to be addressed in the future are also discussed. We searched the PubMed database for original papers written in English. Age restrictions were set for children (birth to 18 years). No limitations were set for the date and study country.
    EXPERT OPINION: Early detection and treatment of respiratory manifestations in SCD should be central to follow-up with patients affected by SCD. Nonetheless, studies are lacking, especially in pediatric age, and there is still no consensus on their management. Further research is strongly needed to accomplish universally accepted guidelines to guarantee patients the best care possible.
    Keywords:  Sickle cell disease; acute chest syndrome; asthma; children; hypoxia; lung function tests; sleep-disordered breathing
    DOI:  https://doi.org/10.1080/17476348.2025.2451960
  2. Haematologica. 2025 Jan 09.
    The modern use of hydroxyurea for children with sickle cell anemia.
    Charles T Quinn, Russell E Ware.
      Over the past 40 years, the introduction and refinement of hydroxyurea therapy has led to remarkable progress for the care of individuals with sickle cell anemia (SCA). From initial small proof-of-principle studies to multi-center Phase 3 controlled clinical trials and then numerous open-label studies, the consistent benefits of once-daily oral hydroxyurea have been demonstrated across the lifespan. Elevated fetal hemoglobin (HbF) serves as the most important treatment response, as HbF delays sickle hemoglobin polymerization and reduces erythrocyte sickling. Increased amounts of HbF, especially when distributed across the majority of erythrocytes, improve clinical outcomes by reducing hemolytic anemia and preventing vasoocclusion, thereby ameliorating both acute and chronic-and overt and covert-complications. Additional benefits of hydroxyurea beyond HbF induction include lower neutrophil and platelet counts, reduced inflammation, and improved rheology. Toxicities of hydroxyurea in SCA are typically mild and predictable; modest cytopenia is expected and actually therapeutic, while occasional gastrointestinal and cutaneous manifestations are well-tolerated. Long-term risks of hydroxyurea for SCA are mainly theoretical but require ongoing surveillance. Accordingly, hydroxyurea should be initiated as part of standard-of-care, ideally in the first year of life. Proper dosing of hydroxyurea is critical, aiming through stepwise dose escalation to achieve modest but safe myelosuppression, with periodic adjustments for weight gain. Precision dosing using pharmacokinetics may facilitate optimal dosing without frequent dose adjustments. Although transformative and even curative therapies for SCA are emerging, hydroxyurea is the only available and accessible disease-modifying treatment that can address the global burden of disease, especially in low-resource settings within sub-Saharan Africa.
    DOI:  https://doi.org/10.3324/haematol.2023.284633
  3. Front Immunol. 2024 ;15 1493904
    Missing the mark(ers): circulating endothelial cells and endothelial-derived extracellular vesicles are elevated in sickle cell disease plasma.
    Joan D Beckman, Ping Zhang, Julia Nguyen, Robert P Hebbel, Gregory M Vercellotti, John D Belcher.
      Sickle cell disease (SCD) is a devastating hemolytic disease, marked by recurring bouts of painful vaso-occlusion, leading to tissue damage from ischemia/reperfusion pathophysiology. Central to this process are oxidative stress, endothelial cell activation, inflammation, and vascular dysfunction. The endothelium exhibits a pro-inflammatory, pro-coagulant, and enhanced permeability phenotype. We used flow cytometry to enumerate circulating endothelial cells (CECs, CD31+/CD45-/CD146+) in SCD and normal healthy control blood samples. Furthermore, we assessed CEC subtypes, including circulating endothelial progenitor cells (EPCs, CD31+/CD45-/CD146+/CD133+) and mature CECs (mCECs, CD31+/CD45-/CD146+/CD133-) with mCECs further subdivided into resting CECs (rCECs, VCAM-1-) and activated CECs (aCECs, VCAM-1+). As compared to healthy controls, total CECs and mCECs were elevated in SCD blood as compared to healthy control blood. Using the same markers along with size-based gating, we also used flow cytometry to enumerate endothelial-derived extracellular vesicles (EEVs) in plasma. We assessed EEV subtypes based on VCAM-1 expression, including activated EEVs (aEEVs, CD31+/CD45-/CD146+/CD133-/VCAM-1+) and resting EEVs (rEEVs, VCAM-1 negative), presumably derived from activated and resting endothelial cells, respectively. aEEVs were elevated in SCD patient plasma as compared to healthy controls. Importantly, in SCD patients, total EEVs and aEEVs were increased during self-reported pain crisis as compared to steady state. Plasma markers of endothelial cell activation including soluble E-selectin, P-selectin, VCAM-1, and ICAM-1 were elevated in SCD plasma. These data highlight strategies to detect SCD-related endothelial cell activation and demonstrate that endothelial cell activation markers may be useful to evaluate curative and non-curative therapies in SCD patients.
    Keywords:  circulating endothelial cells (CEC); endothelium; extracellular vesicles (EVs); sickle cell anemia; sickle cell pain crisis; soluble adhesion molecules
    DOI:  https://doi.org/10.3389/fimmu.2024.1493904
  4. Lancet Haematol. 2025 Jan;pii: S2352-3026(24)00378-8. [Epub ahead of print]12(1): e5-e6
    Re-energising therapy options in sickle cell disease: the mitapivat phase 2 trial results.
    Parul Rai, Jane S Hankins.
      
    DOI:  https://doi.org/10.1016/S2352-3026(24)00378-8
  5. Pediatr Blood Cancer. 2025 Jan 06. e31504
    Influence of Weather on Sickle Cell Disease Vaso-Occlusive Episodes and Acute Chest Syndrome: A Nationwide Sample Analysis.
    Neha J Desai, Ana Lucia Gonzalez-Herrera, Sindhoosha Malay, Tracie Brown, Amma Owusu-Ansah, Sanjay Ahuja.
       BACKGROUND: The clinical manifestations of sickle cell disease (SCD) result in significant morbidity and healthcare costs. The effect of weather as a risk factor for the development of vaso-occlusive episodes (VOEs) has been previously studied, although with variable results. The aim of our retrospective, nationwide study was to determine the association between weather patterns and pediatric VOE and acute chest syndrome (ACS).
    PROCEDURE: Demographic and clinical data were obtained between 2015 and 2022 from the Pediatric Health Information System and merged with weather data from the National Climatic Data Center.
    RESULTS: We observed a higher incidence of VOE and ACS admissions during the colder months. Results also revealed a negative association between VOE admissions and average temperature, whereas a positive association was found for ACS admissions.
    CONCLUSION: Medical providers should continue to counsel patients with SCD to take appropriate precautions during cold weather.
    Keywords:  acute chest syndrome; sickle cell disease; vaso‐occlusive episodes; weather
    DOI:  https://doi.org/10.1002/pbc.31504
  6. Rev Med Interne. 2025 Jan 07. pii: S0248-8663(24)01344-4. [Epub ahead of print]
    [Extramedullary hematopoiesis, a rare complication of sickle cell disease: A six-case series and literature review].
    Ugo Boccadifuoco, Geoffrey Cheminet, Benjamin Morino, Jean-Benoît Arlet.
       INTRODUCTION: Extramedullary hematopoiesis (EMH) is very rarely described during sickle cell disease (SCD). Our aim was to describe six cases of EMH occurring in adult SCD patients and to conduct a literature review.
    METHODS: Retrospective, descriptive, and monocentric study, identifying all cases of EMH recorded in our cohort of adult SCD patients, up to April 2024. A literature review via PubMed included thirty-five articles (44 patients).
    RESULTS: Six patients (4 men, 83.3% with SS genotype [n=5], 1 SC), with a median age of 22 (range 12-64) years at the time of EMH diagnosis were included. Four patients (66.7%) had an aseptic osteonecrosis of the hip. The localization of EMH varied: paravertebral (n=3), peri-articular in the hip (n=1), adrenal (n=1), hepatic (n=1), splenic (n=1) and was similar to the localizations reported in the literature. EMH was symptomatic at diagnosis in half of the cases. The diagnosis was established by histology (n=3/3) and/or typic magnetic resonance imaging (MRI) (n=4/4). The median baseline hemoglobin was 9.1 (extremes 5.8-10.9) g/dL. A watch-and-wait approach was primarily observed.
    CONCLUSION: EMH in SCD patients appears to be rare, with varied localizations. Its diagnosis is made with MRI and/or biopsy, and its treatment is not consensual.
    Keywords:  Aseptic osteonecrosis; Drépanocytose; Dyserythropoiesis; Dysérythropoïèse; Extramedullary hematopoiesis; Hydroxyurea; Hydroxyurée; Hématopoïèse extramédullaire; Ostéonécrose aseptique; Sickle cell disease
    DOI:  https://doi.org/10.1016/j.revmed.2024.12.006
  7. Pediatr Blood Cancer. 2025 Jan 09. e31515
    Major ABO Incompatibility in Non-Myeloablative Hematopoietic Stem Cell Transplant for Sickle Cell Disease-Not an Insurmountable Obstacle.
    Kimberly Ji Eun Chung, Donna A Wall, Kuang-Yueh Chiang.
      With advances in conditioning strategies and graft-versus-host disease (GvHD) prevention, hematopoietic stem cell transplantation (HSCT) is a safe, curative treatment option for pediatric patients with sickle cell disease (SCD). However, donor options have been limited in non-myeloablative matched sibling donor (MSD) setting by excluding recipients with major ABO blood group incompatible donors due to concern of the risk of significant complications such as pure red cell aplasia (PRCA). We present three cases of successful HSCT with major ABO incompatibility with their donors, and discuss strategies to safely expand the donor pool to include these donors.
    Keywords:  ABO incompatible donor; bone marrow transplant; pure red cell aplasia; sickle cell anemia
    DOI:  https://doi.org/10.1002/pbc.31515
  8. Am J Nurs. 2024 Dec 01. 124(12): 61
    Lactated Ringer Instead of Normal Saline Solution for Sickle Cell Vaso-Occlusive Episodes.
    Karen Rosenberg.
      According to this study.
    DOI:  https://doi.org/10.1097/01.NAJ.0001095256.49764.7f
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