bims-sicedi Biomed News
on Sickle cell disease
Issue of 2025–11–30
nine papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo
  1. Oxidantscan: A novel biomarker to assess red blood cell susceptibility to oxidative stress in sickle cell disease.
  2. Red cell physiologic stress results in lower quality transfusions: a randomized trial in adults with sickle cell disease.
  3. Correction: Clinical, laboratory, radiological features, and outcome of acute fat embolism syndrome in sickle cell disease.
  4. Association of cell adhesion molecules levels & single nucleotide polymorphisms with vaso-occlusive crisis in sickle cell disease: A cross sectional study.
  5. Humoral and cellular immune response after COVID-19 vaccination in patients with sickle cell disease on hydroxyurea.
  6. Does cholecystectomy in patients with sickle cell disease reduce vaso-occlusive crises? A study conducted in two referral hospitals in Niger.
  7. Longitudinal changes and predictors of cardiac extracellular volume fraction in sickle cell anemia.
  8. IFN-I-Mediated Transcriptional Reprogramming Drives Myeloid-skewed Hematopoiesis in Sickle Cell Anemia.
  9. Infectious Etiologies and Antimicrobial Management of Acute Chest Syndrome in Adult Sickle Cell Disease Patients: Pathogen Identification Patterns and Clinical Outcomes from a Five-Year Retrospective Study in Eastern Saudi Arabia.
  1. Blood Cells Mol Dis. 2025 Nov 19. pii: S1079-9796(25)00059-2. [Epub ahead of print]117 102967
    Oxidantscan: A novel biomarker to assess red blood cell susceptibility to oxidative stress in sickle cell disease.
    C A Hernández, M J M Traets, W W van Solinge, A W Rijneveld, L Kaestner, T John, E Nur, B J Biemond, F A Kuypers, E J van Beers, M A E Rab, R van Wijk.
      Red blood cells (RBC) from patients with sickle cell disease (SCD) are continuously exposed to high levels of oxidative stress, which impacts RBC deformability. In this study, we applied a novel technique (oxidantscan) to measure deformability of RBCs under shear stress while exposed to oxidative stress. Using RBCs collected from a cohort of patients with SCD and healthy volunteers, we measured different parameters including T-POD (Time to initiate Oxidant-induced change in Deformability) and EIMin (the minimum deformability reached during the test). T-POD was significantly shorter in patients with HbSS (n = 21, 729 ± 410 s) and HbSC (n = 19, 1031 ± 225 s) when compared to healthy controls (n = 20, 1739 ± 328 s, p < 0.05). Also EIMin was significantly lower in patients with HbSS (0.26 ± 0.10) and HbSC (0.30 ± 0.10) compared to healthy controls (0.54 ± 0.02). These results indicate that RBCs from patients with SCD are more susceptible to oxidative stress, which can be measured in a reproducible and quantifiable way. We also demonstrate that Oxidantscan outcome parameters correlated with sickling behavior and markers of hemolysis, indicating a possible link between these key pathophysiological features and the ability to withstand oxidative stress (all p < 0.05). Finally, we provide preliminary evidence for the potential of this technique to evaluate antioxidant therapy with l-glutamine as SCD RBCs showed a significant improvement in T-POD (11.5 %, p = 0.01) and EIMin (46.9 %, p = 0.03) upon ex vivo treatment with l-glutamine. The Oxidantscan is a promising technique for evaluating the response of SCD RBCs to oxidative stress, providing new insights in disease pathophysiology and potential novel treatment strategies.
    Keywords:  Oxidative stress; Oxygen gradient ektacytometry; Red blood cell; Sickle cell disease
    DOI:  https://doi.org/10.1016/j.bcmd.2025.102967
  2. Blood Red Cells Iron. 2025 Dec;pii: 100017. [Epub ahead of print]1(3):
    Red cell physiologic stress results in lower quality transfusions: a randomized trial in adults with sickle cell disease.
    Matthew S Karafin, Ross M Fasano, Anton Ilich, David Wichlan, Ada Chang, Rae Janecke, Stephanie Zellner-Jones, Sonjile M James, Hailly E Butler, Oleg Kolupaev, Melissa C Caughey, Samuel R Wilson, Nigel S Key, Joshua J Field, Jane A Little.
      People with sickle cell disease (SCD) may be transfused with red cell units that are near the end of their storage life, exposing them to components of the red cell storage lesion. This study evaluated the clinical impact of storage age and red cell distress markers on chronically transfused adults with SCD. This randomized prospective clinical trial recruited 26 chronically transfused adult patients (aged >16 years) with SCD; 13 participants were randomized to each study arm, that is, targeted to receive only ≥30-day or ≤10-day stored red cell units for 3 consecutive outpatient transfusion events. The red cell units were evaluated via quantification of surface exposure of phosphatidylserine (PS) and phosphatidylethanolamine (PE). Differences in key clinical variables were also evaluated. We show that patients receiving units with higher surface-exposed PS and PE, regardless of storage age, had a reduced hemoglobin (Hb) increment at 2 weeks (PS-PE high, 0.59 g/dL; PS-PE low, 1.04 g/dL; P = .04), increased pain crises (incidence rate ratio, 7.44; 95% confidence interval [CI], 1.53-36.25), and higher odds of reported illness (odds ratio, 1.94; 95% CI, 1.06-3.54). Furthermore, posttransfusion serum iron predicted subsequent subjective symptoms of illness (receiver operating characteristic-area under the curve, 0.76) and correlated with smaller increases in HbA percent after transfusion (r =-0.36; P = .04). These data suggest that the physiologic state of transfused red cells may deleteriously affect patient outcomes. Future studies focusing on identifying and then avoiding lower-quality red cell units in high-risk patients with SCD could enhance patient safety. This trial was registered at www.clinicaltrials.gov as #NCT03704922.
    DOI:  https://doi.org/10.1016/j.brci.2025.100017
  3. Sci Rep. 2025 Nov 26. 15(1): 42104
    Correction: Clinical, laboratory, radiological features, and outcome of acute fat embolism syndrome in sickle cell disease.
    Alkindi Salam, Raniga Sameer, Al-Ajmi Eiman, Al-Farsi Khalil, Khan Hammad, Nuzhat Khaleeq Unnisa, Al-Busaidi Mujahid, Al-Azri Faisal, Gujjar Arunodaya, Al-Asmi Abdullah, Al-Maawali Anwaar, Ramachandiran Nandhagopal, Pathare Anil.
      
    DOI:  https://doi.org/10.1038/s41598-025-24320-0
  4. Indian J Med Res. 2025 Sep;pii: 10.25259/IJMR_406_2025. [Epub ahead of print]162(3): 389-398
    Association of cell adhesion molecules levels & single nucleotide polymorphisms with vaso-occlusive crisis in sickle cell disease: A cross sectional study.
    Parul Gupta, Pankaj Asati, Asha Tiwari, Ravindra Kumar.
      Background & objectives Sickle cell disease (SCD) is a monogenic disorder characterised by aberrant haemoglobin production, leading to haemolytic anaemia and vaso-occlusive crises. Genetic variations and altered expression of cell adhesion molecules (CAMs) are implicated in disease pathogenesis. This cross-sectional study investigated the association between single nucleotide polymorphisms (SNPs) in the SELP, SELE, ICAM-1, and VCAM-1 genes and their protein levels in individuals with SCD. Methods A total of 140 individuals with SCD were recruited. Plasma levels of P-selectin, E-selectin, ICAM-1 and VCAM-1 were measured by ELISA method alongside a control group (n=10). The selected SNPs of SELP, SELE, ICAM-1, and VCAM-1 genes were identified through Sanger sequencing method. Results The expression of adhesion molecules were found to be significantly higher in SCD group as compared to control. Furthermore, the results showed significant associations between SNPs, SELE: c.109+138A>C (P<0.0001), SELE: c.422-25T>C (P<0.0001), and SELE: c.529+15T>C (P=<0.0001) with vaso-occlusive crises even after Bonferroni correction (corrected P=0.0025). Interpretation & conclusions Significant correlation observed between SELP, SELE, and VCAM-1 levels suggests complex interactions of these markers that may influence disease progression and identify potential therapeutic targets for managing SCD complications. Further studies are warranted to validate these findings in larger cohorts and explore the functional implications of the observed genetic and molecular associations in SCD.
    Keywords:  Cell adhesion molecules; sickle cell disease; single nucleotide polymorphisms; vaso-occlusive crisis
    DOI:  https://doi.org/10.25259/IJMR_406_2025
  5. Blood Adv. 2025 Nov 26. pii: bloodadvances.2025017239. [Epub ahead of print]
    Humoral and cellular immune response after COVID-19 vaccination in patients with sickle cell disease on hydroxyurea.
    Sabine Haggenburg, Cilia R Pothast, Quincy Hofsink, Nienke J E Haverkate, Michel S Bhoekhan, Mathieu Claireaux, Rob S van Binnendijk, Gerco den Hartog, Birgit I Lissenberg-Witte, Rory D de Vries, Charlotte F J Van Tuijn, Bart J Biemond, Erfan Nur, Corine GeurtsvanKessel, Pim G N J Mutsaers, Annoek E C Broers, Abraham Goorhuis, Inger S Nijhof, Marit van Gils, Mirjam H M Heemskerk, Mette D Hazenberg, Caroline E Rutten.
      Patients with sickle cell disease (SCD) are at increased risk of COVID-19-related mortality compared to healthy individuals, also after vaccination. To what extent impaired vaccine-induced immunity contributes to this risk is unknown. We prospectively investigated vaccine immunogenicity in 31 COVID-19 mRNA vaccinated patients with SCD. All patients used hydroxyurea. We quantified humoral and cellular immune responses four weeks after second and third vaccination and compared results with age-, sex- and vaccine-matched healthy individuals. Irrespective of higher naive and lower memory subsets of B cells, serum neutralizing spike glycoprotein 1 (S1) IgG antibody concentrations and frequencies of spike-specific memory B cells were similar to healthy individuals at each timepoint. Frequencies of CD4+ and CD8+ T cells in patients with SCD were also comparable to controls, however type 1 cytokine production by spike-specific T cells was reduced. Reduced cytokine production and lower antibody production correlated with higher serum fetal hemoglobin levels, suggesting an association with the use of hydroxyurea. Whereas a third vaccination improved neutralizing antibody and memory B cell responses, Th1 cytokine production tended to remain lower in patients compared to controls. Our data point towards delayed or reduced vaccine-induced immunity, in line with previous reports, which may contribute to the increased risk for COVID-19 related mortality reported in these patients. Clinical Trial: NL-OMON51241, CCMO.nl.
    DOI:  https://doi.org/10.1182/bloodadvances.2025017239
  6. J Visc Surg. 2025 Nov 25. pii: S1878-7886(25)00202-4. [Epub ahead of print]
    Does cholecystectomy in patients with sickle cell disease reduce vaso-occlusive crises? A study conducted in two referral hospitals in Niger.
    Adama Saïdou, Yahouza Boka Tounga, Kadi Ide, Abdoulaye Maman Bachir, Oudou Aliou Zabeirou, Rachid Sani.
      The objective of this study was to report on the results of cholecystectomy in patients with sickle cell disease in two hospitals in Niger.
    PATIENTS AND METHODS: This was a retrospective study conducted over a six-year period in the general referral hospital and the national hospital of Niamey (Niger).
    RESULTS: We collected data concerning 56 cases of cholecystectomy in patients with sickle cell disease, representing of 10.3% of all cholecystectomies (gall bladder removals) performed. A majority of the patients were female (55.4%), with a mean age of 20.2 years, standard deviation of 8.8, and extreme values at 6 and 47 years. Homozygous SS forms of sickle cell disease predominated (92.9%). Nearly two-thirds of the patients (64.3%) were referred from the national sickle cell disease referral center. The main operative indication (69.6%) was symptomatic gall bladder (vesicular) lithiasis. All of the patients were anemic, with severe anemia in nearly half (44.6%). Exchange transfusion was carried out in 42.9% of the patients, and perioperative blood transfusion in 57.1%. The laparoscopic route was followed in almost all of the patients (94.6%). Mean postoperative stay in an intensive care unit was 23.5±7.2 (12-48) 48hours. The rate of postoperative complications was 23.2%, and the rate of mortality was 1.8%. As regards disease progress at one year, no vaso-occlusive crises were observed in seven eight (87.5) of the patients.
    CONCLUSION: Cholecystectomy in sickle cell patients calls for a multidisciplinary strategy, and laparoscopy appears to be the ideal approach, especially insofar as it provides satisfactory postoperative comfort.
    Keywords:  Cholecystectomy; Niger; Sickle cell disease
    DOI:  https://doi.org/10.1016/j.jviscsurg.2025.11.004
  7. Blood Red Cells Iron. 2025 Dec;pii: 100031. [Epub ahead of print]1(3):
    Longitudinal changes and predictors of cardiac extracellular volume fraction in sickle cell anemia.
    Omar Niss, Cara E Morin, Sassan Hashemi, Tarek Alsaied, Sean M Lang, Michael D Taylor, MacKenzie Tasset, Punam Malik, Charles T Quinn.
      Diffuse myocardial fibrosis is a key feature of the cardiomyopathy of sickle cell anemia (SCA) that is linked to diastolic dysfunction. Cardiac MRI (CMR)-derived extracellular volume fraction (ECV) is a quantitative biomarker of myocardial fibrosis that is elevated in SCA. The stability of ECV in SCA and its clinical associations over time are unknown. To measure longitudinal changes in ECV, without specific intervention, and identify correlates of ECV change in patients with SCA, we conducted a prospective, 2-year study involving annual CMR, echocardiography, and laboratory assessments in 24 patients with SCA (mean age 21.4±10 years). ECV was calculated using T1 mapping pre- and post-gadolinium, and extracellular matrix and cellular volumes were calculated to account for relative changes. Diastolic function was classified by echocardiography. Longitudinal associations were assessed using linear mixed-effects models. ECV was abnormally increased at baseline and remained stable over time (mean change -1.1±2.7% per year). Intra-subject ECV variability was low (mean 2.4%), with no differences by age or sex. ECV correlated with diastolic dysfunction at all timepoints (P=0.01). Changes in ECV were more closely associated with changes in extracellular matrix volume (P=0.01) than with myocardial cell volume. In a longitudinal multivariable analysis, ECV was independently associated with diastolic dysfunction, hemoglobin, NT-proBNP, left atrial volume, and peak pulmonary artery velocity. In summary, ECV is a stable and reliable metric of myocardial extracellular matrix expansion in SCA. Its strong associations with diastolic dysfunction and biomarkers of cardiac stress support its use as an imaging biomarker for antifibrotic therapies in SCA. This trial was registered at www.ClinicalTrials.gov as #NCT02410811.
    DOI:  https://doi.org/10.1016/j.brci.2025.100031
  8. Res Sq. 2025 Oct 07. pii: rs.3.rs-7766748. [Epub ahead of print]
    IFN-I-Mediated Transcriptional Reprogramming Drives Myeloid-skewed Hematopoiesis in Sickle Cell Anemia.
    Marion Serra, Marine Aglave, Mohammad Salma, Steven Akkaya, Patricia Hermand, Carine Lefevre, Romain Duval, Jade Merrer, Fallou Leye, Joelle Magne, Isabelle Plo, Lionel Blanc, Eric Soler, Slim Azouzi, Berengere Koehl.
      Neutrophils and monocytes are persistently elevated in sickle cell anemia (SCA), yet the intrinsic mechanisms driving pathological myelopoiesis and inflammation remain poorly defined. Through single-cell RNA sequencing and functional assays, we demonstrate that hematopoietic stem and multipotent progenitor cells (HSPCs) in SCA are transcriptionally reprogrammed toward myeloid differentiation. This process is orchestrated by aberrant activation of type I interferon (IFN-I) signaling, which promotes premature myeloid commitment of hematopoietic stem cells. SCA progenitors further exhibit unexpected responsiveness to granulocyte colony-stimulating factor (G-CSF) through upregulation of CSF3R, resulting in skewed myelopoiesis toward the monocytic lineage. Importantly, hydroxyurea treatment attenuates IFN-I signaling in neutrophils, consistent with its therapeutic role in reducing excessive inflammation and granulopoiesis. Collectively, these findings uncover IFN-I-driven remodeling of hematopoiesis as a fundamental mechanism of leukocytosis and chronic inflammation in SCA, and establish a tractable therapeutic axis to mitigate innate immunity activation in this disease.
    DOI:  https://doi.org/10.21203/rs.3.rs-7766748/v1
  9. Pathogens. 2025 Nov 18. pii: 1174. [Epub ahead of print]14(11):
    Infectious Etiologies and Antimicrobial Management of Acute Chest Syndrome in Adult Sickle Cell Disease Patients: Pathogen Identification Patterns and Clinical Outcomes from a Five-Year Retrospective Study in Eastern Saudi Arabia.
    Ali Alsaeed, Reda Aleid, Omar Amin, Amjad Alansari, Hadi Aleid, Mohammed Aleid.
      Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD) with complex infectious and non-infectious etiologies. Bacterial pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and atypical organisms such as Mycoplasma pneumoniae, play crucial roles in ACS pathogenesis, particularly in immunocompromised SCD patients with functional asplenia. Despite the importance of infectious triggers, regional data on pathogen identification rates and antimicrobial management strategies in ACS remain limited, especially from high-prevalence SCD regions. This study aimed to investigate the infectious etiologies, pathogen identification patterns, and antimicrobial management outcomes of ACS in adult SCD patients in Eastern Saudi Arabia. A five-year retrospective analysis was conducted on patients aged ≥14 years with SCD who were admitted with ACS to Dammam Medical Complex between 2018 and 2022. Comprehensive microbiological evaluation included blood cultures, sputum cultures, and atypical pathogen testing (Mycoplasma pneumoniae, Chlamydia pneumoniae). Data on antimicrobial regimens, pathogen identification rates, vaccination status against encapsulated bacteria, and clinical outcomes were systematically analyzed. Empirical antibiotic strategies and their effectiveness in this immunocompromised population were evaluated. A total of 60 adult SCD patients experiencing 80 episodes of ACS were included. Despite comprehensive microbiological workup, specific infectious pathogens were identified in only 8 (10.0%) episodes, highlighting the complex multifactorial etiology of ACS. Blood cultures yielded pathogens in 5 (6.3%) cases, sputum cultures in 4 (5.0%) cases, and Mycoplasma pneumoniae was identified in 3 (3.8%) episodes. All patients received empirical broad-spectrum antimicrobial therapy, with ceftriaxone and azithromycin combination being the most frequent regimen (76 cases, 95.0%), providing coverage for both typical and atypical bacterial pathogens. Antibiotic escalation was required in 16 (20.0%) episodes. Vaccination rates against Streptococcus pneumoniae were suboptimal at 30 (50.0%), representing a significant risk factor for invasive bacterial infections in this functionally asplenic population. The intensive care unit (ICU) admission rate was 15 (18.8%), and in-hospital mortality was 3 (3.8%), with infectious complications contributing to severe outcomes. In this cohort of SCD patients, ACS demonstrated low rates of specific pathogen identification despite systematic microbiological investigation, supporting the multifactorial infectious and non-infectious etiology of this syndrome. The predominant use of broad-spectrum antimicrobial therapy targeting both typical and atypical bacterial pathogens proved effective in this immunocompromised population. However, suboptimal vaccination rates against encapsulated bacteria represent a critical gap in infection prevention strategies. These findings emphasize the importance of empirical antimicrobial coverage for suspected bacterial pathogens in ACS management and highlight the urgent need for enhanced vaccination programs to prevent infectious complications in functionally asplenic SCD patients.
    Keywords:  Mycoplasma pneumoniae; acute chest syndrome; antimicrobial therapy; bacterial pathogens; immunocompromised host; infectious complications; sickle cell disease; vaccination
    DOI:  https://doi.org/10.3390/pathogens14111174
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