bims-sicedi Biomed News
on Sickle cell disease
Issue of 2024‒10‒27
fourteen papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo



  1. Eur J Haematol. 2024 Oct 21.
      Voxelotor modifies hemoglobin-oxygen affinity improving anemia and reducing hemolysis in sickle cell patients. However, the impact of Voxelotor on fetal hemoglobin (HbF) levels is unknown. We describe here variations of percentage of HbF measured by high performance liquid chromatography and mean corpuscular fetal Hb in a cohort of sickle cell patients treated with Voxelotor at Henri Mondor Sickle Cell Referral Center. Our data show a decrease in HbF levels in sickle cell patients after 6 months of treatment with Voxelotor, which is likely to be associated with an increase in the lifespan of red blood cells that are no longer prematurely removed from the circulation, particularly those with low HbF. This work raises the question of the risk of a rebound effect when stopping Voxelotor, which has a short half-life, during the time it takes to increase HbF.
    Keywords:  Voxelotor; fetal hemoglobin; hematopoiesis; sickle cell disease
    DOI:  https://doi.org/10.1111/ejh.14332
  2. Vox Sang. 2024 Oct 22.
      BACKGROUND AND OBJECTIVES: This review aims to explore the impact of sickle cell disease (SCD) on patients' quality of life (QoL) and the effectiveness of different transfusion modalities, particularly automated red blood cell exchange (aRBCX), in managing the factors that impact QoL.MATERIALS AND METHODS: A systematic search was performed in PubMed to retrieve articles with data on QoL in SCD patients treated with aRBCX during the last 20 years. A targeted search for medical guidelines and a free search were added.
    RESULTS: When assessing the impact of the transfusion modality on the QoL of patients with SCD, some studies indicated an improvement in health-related QoL when using aRBCX while others reported no differences. The benefits of aRBCX include a decrease in length of hospital stay, pain-related hospitalizations and procedure time. The drawbacks of aRBCX were also identified, including an increased number of procedure-related complications (despite the overall number of complications showing no significant differences) and a more complex vascular access. Chronic red blood cell exchange favours psychosocial factors such as anxiety and social functioning, but the impact of using aRBCX in these parameters is not determined yet.
    CONCLUSION: aRBCX, known to be an efficient procedure to manage SCD, appears to be promising in improving patients' QoL. However, more comprehensive studies incorporating patient-reported outcomes are needed to fully understand the impact of different transfusion modalities on QoL in SCD patients. An integrated care approach, including psychological support and pain management, may further enhance QoL.
    Keywords:  Spectra Optia; apheresis; quality of life; red blood cell exchange; sickle cell disease
    DOI:  https://doi.org/10.1111/vox.13757
  3. Cureus. 2024 Sep;16(9): e70087
      Background Sickle cell disease (SCD) and iron deficiency anemia (IDA) are significant global health concerns, particularly in pediatric populations. This study investigates the prevalence, clinical impact, and management challenges of IDA in children with SCD. Methods A prospective observational study was conducted at the Department of Pediatrics, Jawaharlal Nehru Medical College (JNMC) and Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi, from June 2022 to May 2024. The study included 60 children diagnosed with SCD. Comprehensive assessments were performed, including medical histories, physical examinations, and hematological investigations. Diagnosis of IDA was based on hemoglobin levels, mean corpuscular volume (MCV), red cell distribution width (RDW), peripheral blood smears, serum iron levels, and serum ferritin concentrations. Results Of the 60 participants, 15% exhibited iron deficiency. No significant gender differences were found in iron deficiency status. A significant association was observed between SCD type and the presence of pallor (p = 0.025) and sickle cell crises (p = 0.023). The study also found no significant association between SCD type and the presence of organomegaly (p = 0.079) or iron deficiency status (p = 0.675). The mean hemoglobin levels varied across SCD types, with sickle cell anemia patients showing lower levels than those with sickle cell trait or disease. Conclusion Diagnosing and managing IDA in children with SCD is complex due to overlapping hematological features and the risk of iron overload from frequent transfusions. Tailored diagnostic and therapeutic approaches are essential to improving hemoglobin levels, reducing complications, and enhancing the quality of life for affected children. This study provides valuable insights for refining clinical practices and emphasizes the need for a multidisciplinary approach to managing these intertwined conditions.
    Keywords:  cariology; folic acid deficiency; iron deficiency; organomegaly; sickle cell disease
    DOI:  https://doi.org/10.7759/cureus.70087
  4. Br J Haematol. 2024 Oct 22.
      Allogeneic haematopoietic cell transplantation (HCT) with HLA-matched sibling donor remains the most established curative therapeutic option for patients with sickle cell disease (SCD). However, it is not without risks, highlighting the need for a risk stratification system. Utilizing a machine learning (ML) approach that combines clinical and imaging variables, we identified red cell distribution width and renal organ damage as important risk factors for patients undergoing HCT. This ML-based algorithm, similar to an approach previously reported for predicting mortality in patients with SCD, should be applicable to risk factor discovery in similar studies.
    Keywords:  haemopoietic cell transplant; machine learning; mortality; risk assessment; sickle cell disease
    DOI:  https://doi.org/10.1111/bjh.19842
  5. Int J Gynaecol Obstet. 2024 Oct 25.
      OBJECTIVE: Sickle cell disease (SCD) is associated with complications during pregnancy and can negatively influence maternal outcomes. Our study aimed to determine the prevalence and predictors of maternal morbidity among participants enrolled in an eight-site SCD Implementation Consortium (SCDIC) registry.METHODS: We conducted a cross-sectional analysis of female registry participants, aged 15-45 years, with a confirmed diagnosis of SCD. Participants completed a survey of self-reported pregnancies and outcomes.
    RESULTS: Seven hundred and thirty-eight individuals had at least one pregnancy event, with 1076 live births. Twenty percent reported a pregnancy loss or fetal demise. Of the 1076 live births, 75% involved at least one complication. The most prevalent complications were pain crises (61.1%) and pregnancy requiring blood transfusion(s) (33.0%). Multiparous individuals with a prior occurrence of a complication in a previous pregnancy had higher odds of recurrence of the same complication in subsequent pregnancies (i.e., previous acute crisis was associated with subsequent acute pain events odds ratio [OR]: 3.13; 95% confidence interval [CI]: 2.06-4.76) and prior transfusion requiring another transfusion (OR: 3.22; 95% CI: 2.01-5.16).
    CONCLUSION: Individuals reported a high prevalence of pregnancy loss and maternal complications. Our findings underscore the importance of preconception counseling and early initiation of perinatal care in SCD.
    Keywords:  fertility; pregnancy; pregnant women; sickle cell
    DOI:  https://doi.org/10.1002/ijgo.15974
  6. Hematol Transfus Cell Ther. 2024 Oct 08. pii: S2531-1379(24)02815-3. [Epub ahead of print]
      BACKGROUND: Sickle cell disease is the most common inherited blood disorder in the world with the birth of approximately 300,000 newborns screened each year. In 2009, the World Health Organization ranked the fight against sickle cell disease among the priorities for the Africa regions. The best way to prevent this incurable disease remains, on one hand systematic screening at birth, and on the other the proscription of risky union between heterozygous subjects.AIM: The aim of this study was to analyze the epidemiological profile of sickle cell disease and other hemoglobinopathies in Benin and determine more up-to-date prevalence rates of the disease within the population.
    METHODS: The hemoglobin profiles of 2910 study participants were determined by quantitative electrophoresis. Samples with abnormal hemoglobin results were subjected to a complete blood count.
    RESULTS: Our study population was balanced between males (1528) and females (1382) with a sex ratio of 1.1. The mean age ranged from eight years in the pediatric group to 26 years in adults. The hemoglobin electrophoresis profiles found were as follows: 59.7 % Hb AA (normal), 21.7 % Hb AS, 10.2 % Hb AC, 3.1 % Hb SS, 3.7 % Hb SC, and 1.6 % of the rare phenotypes (Hb AD, Hb AE, Hb AF, Hb A/β-thal, Hb SD, Hb SF, Hb CC and Hb C/β-thal). Participants with abnormal hemoglobin presented a normochromic normocytic anemia. A total of 356 (12 %) people knew their profile compared to 2554 (88 %) who did not.
    CONCLUSION: The high prevalence of hemoglobinopathies found in this study highlights in importance of screening in the Benin population.
    Keywords:  Morbidity; Mortality; Prevention; Screening; Sickle cell disease
    DOI:  https://doi.org/10.1016/j.htct.2024.07.008
  7. Iran J Public Health. 2024 Jun;53(6): 1404-1415
      Background: Sickle cell disease (SCD) is one of the hematological disorders characterized by a defect in the structure and function of globin chains. Hereditary factors play an important role in the pathogenesis of SCD. We aimed to investigate the genes and pathways related to the pathogenesis of SCD.Methods: Microarray dataset was downloaded from the Gene Expression Omnibus (GEO) database. LIMMA package of R-software was used to detect UP and Down regulations between SCD and control subjects. Enrichment analysis and Protein-protein interaction (PPI) networks were performed using GeneCodis4 software and GeneMANIA database, respectively. PrognoScan database was used to evaluate the relationship between the hub genes and patients' survival.
    Results: Overall, 447 DEGs were identified in SCD patients compared to control subjects. Out of 447 DEGs, 345 genes were up-regulated and 102 genes were down-regulated. Effective hub genes in SCD pathogenesis include SLC4A1, DTL, EPB42, SNCA, and TOP2A. In addition, hub genes had a high diagnostic value.
    Conclusion: Evaluation of hub genes in SCD can be used as a diagnostic panel to detect high-risk patients. In addition, by identifying the UP and Down stream pathways, treatment strategies in the monitoring and treatment of patients can be designed.
    Keywords:  Gene; Molecular pathway; Pathogenesis; Sickle cell
  8. Int J Neonatal Screen. 2024 Oct 03. pii: 69. [Epub ahead of print]10(4):
      In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence of SCD and related hemoglobinopathies in Catalonia and the change in clinical events occurring after introducing NBS. Screening 506,996 newborns from 2015 to 2022, we conducted a retrospective multicenter study including 100 screened (SG) and 95 unscreened (UG) SCD patients and analyzed SCD-related clinical events over the first six years of life. We diagnosed 160 cases of SCD, with an incidence of 1 in 3169 newborns. The SG had a significantly lower median age at diagnosis (0.1 y vs. 1.68 y, p < 0.0001), and initiated penicillin prophylaxis (0.12 y vs. 1.86 y, p < 0.0001) and hydroxyurea treatment earlier (1.42 y vs. 4.5 y, p < 0.0001). The SG experienced fewer median SCD-related clinical events (vaso-occlusive crisis, acute chest syndrome, infections of probable bacterial origin, acute anemia requiring transfusion, acute splenic sequestration, and pathological transcranial Doppler echography) per year of follow-up (0.19 vs. 0.77, p < 0.0001), a reduced number of annual emergency department visits (0.37 vs. 0.76, p < 0.0001), and fewer hospitalizations (0.33 vs. 0.72, p < 0.0001). SCD screening in Catalonia's NBS program has effectively reduced morbidity and improved affected children's quality of life.
    Keywords:  clinical events; hemoglobinopathies; newborn screening; sickle cell disease; treatment intervention
    DOI:  https://doi.org/10.3390/ijns10040069
  9. EClinicalMedicine. 2024 Oct;76 102839
      Background: Anaemia in sickle cell disease (SCD) is a significant cause of morbidity and mortality, but few studies have reported on the burden and outcome of very severe anaemia. This study described the epidemiology of very severe anaemia by determining the prevalence and incidence, investigating associated clinical and laboratory factors, and assessing outcomes in SCD.Methods: A 10-year prospective cohort study involving SCD patients of all ages was conducted at Muhimbili National Hospital in Tanzania between 2004 and 2013. SCD included Homozygous SS-Sickle cell anaemia and Sβ0 thalassemia at clinics and during hospitalization visits. Very severe anaemia was defined as Haemoglobin <5 g/dL at steady-state which was a period when a patient was stable with no blood transfusion in past 3 months or accute pain report in the previous month.
    Findings: There were 28,293 (92.9%) clinic visits and 2158 hospitalisations amongst 3586 patients. Mean haemoglobin concentration at clinic was 7.4 g/dL, (95% CI: 7.4-7.5) compared to hospitalisation [6.4 g/dL, 95% CI: 6.3-6.5], p < 0.001. Prevalence of very severe anaemia at the clinic was 4.1%, and 23.8% during hospitalization, while the overall incidence was 114.1 (95% CI: 108.2-120.2) events per 1000 person years. Risk ratio of dying for patients with very severe anaemia was 4.78 times higher (95% CI: 3.65-6.25, p < 0.001) than in individuals without very severe anaemia. The risk ratio for mortality was highest in children aged <2 years, and was decreasing steadily with increase in age, from HR = 0.73 (95% CI: 0.39-1.35) in children aged 2-4 years to HR of 0.38 (95% CI: 0.20-0.71) in patients in age group 10-17 years when compared to those aged 0-1 years. Mortality risk ratio was higher (HR = 6.76 [95% CI: 4.31-10.62, p < 0.001]) in patients with steady-state haemoglobin <5 g/dL and presenting with very severe anaemia before death compared to those with steady state haemoglobin ≥5 g/dL and haemoglobin ≥5 g/dL before death.
    Interpretation: The burden of very severe anaemia in SCD was high, especially during hospitalization, and was independent predictor of mortality. There is an urgent need to improve prevention, diagnosis, and interventions for very severe anaemia in SCD in Africa. More research to elucidate the aetiology and mechanisms of anaemia in this population is required.
    Funding: Government of the United Republic of Tanzania, Wellcome Trust, United Kingdom (JKM 072064; Project grant 080025, Strategic award 084538).
    Keywords:  Morbidity; Mortality Tanzania; Sickle cell anaemia
    DOI:  https://doi.org/10.1016/j.eclinm.2024.102839
  10. Proc Natl Acad Sci U S A. 2024 Oct 29. 121(44): e2414437121
      The clearance of senescent and altered red blood cells (RBCs) in the red pulp of the human spleen involves sequential processes of prefiltration, filtration, and postfiltration. While prior work has elucidated the mechanisms underlying the first two processes, biomechanical processes driving the postfiltration phagocytosis of RBCs retained at interendothelial slits (IES) are still poorly understood. We present here a unique computational model of macrophages to study the role of cell biomechanics in modulating the kinetics of phagocytosis of aged and diseased RBCs retained in the spleen. After validating the macrophage model using in vitro phagocytosis experiments, we employ it to probe the mechanisms underlying the kinetics of phagocytosis of mechanically altered RBCs, such as heated RBCs and abnormal RBCs in hereditary spherocytosis (HS) and sickle cell disease (SCD). Our simulations show pronounced deformation of the flexible and healthy RBCs in contrast to minimal shape changes in altered RBCs. Simulations also show that less deformable RBCs are engulfed faster and at lower adhesive strength than flexible RBCs, consistent with our experimental measurements. This efficient sensing and engulfment by macrophages of stiff RBCs retained at IES are expected to temper splenic congestion, a common pathogenic process in malaria, HS, and SCD. Altogether, our combined computational and in vitro experimental studies suggest that mechanical alterations of retained RBCs may suffice to enhance their phagocytosis, thereby adapting the kinetics of their elimination to the kinetics of their mechanical retention, an equilibrium essential for adequately cleaning the splenic filter to preserve its function.
    Keywords:  biomechanics; erythrophagocytosis; hypersplenism; macrophages; splenic sequestration
    DOI:  https://doi.org/10.1073/pnas.2414437121
  11. Osteoporos Int. 2024 Oct 22.
      Low bone mineral density is highly prevalent in sickle cell disease (SCD); whether bisphosphonates can safely preserve or increase bone mass in SCD adults remains unknown. In this study, lumbar spine bone density remained stable with alendronate use, and treatment-related side effects were mostly mild and self-limited.PURPOSE: To describe the effects of alendronate in adults with sickle cell disease (SCD) and osteoporosis.
    METHODS: We reviewed retrospective clinical data from adults with SCD and osteoporosis treated with alendronate at a single center in Brazil (2009-2019). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) of the lumbar spine, femoral neck, and total hip. We analyzed BMD changes by alendronate treatment duration (months), stratified by sex, skeletal site, and SCD genotype.
    RESULTS: Sixty-four SCD adults with osteoporosis (69% females, 73% HbSS, mean age ± standard deviation 42.4 ± 10.9 years) received alendronate for a median (interquartile range) of 48 (29, 73) months. Compared with males, females had significantly lower baseline BMD (g/cm2) at the femoral neck (0.72 vs 0.85, p =  < 0.001) and total hip (0.79 vs 0.88, p = 0.009). The between-sex differences in BMD changes were insignificant. Mean lumbar spine BMD significantly changed by 0.0357 g/cm2 (p = 0.028) in those on alendronate for > 5 years. Four adults (6.3%) reported mild therapy-related side effects. An atypical femoral diaphysis fracture, attributed to alendronate, was incidentally noted in a 37-year-old man on treatment for 4 years.
    CONCLUSION: In this retrospective cohort of adults with SCD and osteoporosis on alendronate for a median of 48 months, we found no significant interactions between sex and changes in lumbar spine, femoral neck, or total hip BMD with alendronate. Lumbar spine BMD was stable in those on alendronate for < 5 years. Side effects of alendronate were mild, though one patient developed an atypical femoral fracture.
    Keywords:  Alendronate; Bisphosphonates; Bone mass; Bone mineral density; Osteoporosis; Sickle cell disease
    DOI:  https://doi.org/10.1007/s00198-024-07268-1