bims-sicedi Biomed News
on Sickle cell disease
Issue of 2025–03–09
eleven papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo
  1. Mechanistic insights on sickle cell disease.
  2. Investigating the impact of sickle cell disease on red blood cell transport in complex capillary networks.
  3. Transformative CRISPR-Cas9 Technologies: A Review of Molecular Mechanisms, Precision Editing Techniques, and Clinical Progress in Sickle Cell Disease.
  4. A young adult clinic to support integration into adult sickle cell disease care: If you build it, they will come.
  5. Plasma oxylipins in children with sickle cell disease: Associations with biomarkers of inflammation and endothelial activation.
  6. Haplotype-Specific Genetic Epidemiology of Sickle Cell Anemia Patients in Accra, Ghana: Patterns, Clinical Implications, and Public Health Responses.
  7. FLT1 and other candidate fetal haemoglobin modifying loci in sickle cell disease in African ancestries.
  8. Hereditary Pyropoikilocytosis as a Modifier of Sickle Cell Disease Severity.
  9. Nocturnal hemoglobin desaturation in chronically transfused adults with sickle cell disease: a retrospective study.
  10. Assessing and managing iron deficiency anemia in sickle cell disease: Insights from a systematic review and meta-analysis.
  11. Factors associated with early return visits to the emergency department in patients with vaso-occlusive crisis.
  1. Lab Anim (NY). 2025 Mar;54(3): 60
    Mechanistic insights on sickle cell disease.
    Jorge Ferreira.
      
    DOI:  https://doi.org/10.1038/s41684-025-01528-1
  2. Annu Int Conf IEEE Eng Med Biol Soc. 2024 Jul;2024 1-4
    Investigating the impact of sickle cell disease on red blood cell transport in complex capillary networks.
    Runxin Wu, Mohammed Shihab Kabir, George A Truskey, Amanda Randles.
      Sickle cell disease encompasses a variety of inherited red blood cell (RBC) disorders characterized by abnormal thrombosis, microvascular occlusion, end-organ ischemia, and early mortality. Understanding how sickle RBCs drive abnormal blood flow and stress on the endothelial wall is essential to predict and prevent blockages in blood circulation. While there are studies comparing blood flow velocity and pressure via computational fluid dynamics simulations, there are still open questions about how sickle cells interact with plasma in a complex capillary network. In order to quantify the hemodynamic differences between normal and sickle cells, we introduced a sickle cell RBC model to massively parallel fluid-structure interaction software HARVEY. Notably, sickle RBCs exhibit increased margination, aggregation at the inner curvature, slower fluid velocity, higher pressure, and greater wall shear stress at standard hematocrit levels. This computational model facilitates detailed cellular modeling for hemodynamic simulations in complex capillary networks, offering predictive insight into blockage and potential vessel ruptures in patients with sickle cell disease.
    DOI:  https://doi.org/10.1109/EMBC53108.2024.10781578
  3. Curr Drug Metab. 2025 Mar 05.
    Transformative CRISPR-Cas9 Technologies: A Review of Molecular Mechanisms, Precision Editing Techniques, and Clinical Progress in Sickle Cell Disease.
    Komal, Prabhjot Kaur, Nidhi Arora, Jyotiram A Sawale, Amandeep Singh.
      Sickle cell disease (SCD) is a hereditary blood disorder resulting from the production of distorted hemoglobin molecules that cause red blood cells to adopt a sickle or crescent-like shape. This disease affects millions of people, particularly those of African, Mediterranean, Middle Eastern, or South Asian descent. In recent years, however, advancements in the CRISPR-Cas9 gene-editing systems have surged. CRISPR stands for clustered regularly interspaced short palindromic repeats, referring to a specific organization of short, partially repeated DNA sequences in prokaryotic genomes. The CRISPR-Cas9 technique is based on the type II CRISPR system of bacteria and involves the Cas9 nuclease, which is targeted to a particular genome section with the help of single-guide RNA. Initially used for random mutations and small sequence alterations, genome editing methods have advanced to achieve large-scale DNA segment manipulation. The BE and PE-- type CRISPR-Cas9 genome editing variants provide new therapeutic options for genetic disorders, improving patients' prognosis. Curative gene editing using CRISPR-Cas9 technology to correct HBB gene mutations that cause SCD represents a revolutionary therapeutic development. These advances bring new hope to patients with previously untreatable diseases, potentially offering a future where genetic disorders can be addressed at their roots. A major objective of CRISPR technology is to enhance its precision and speed, both critical for effective gene editing. This review focuses on molecular mechanisms of CRISPR-Cas9 technology, CRISPR-- Cas9-based approaches for HBB gene modification, clinical trials, patients with sickle cell disease, and advances in CRISPR technology for sickle cell disease.
    Keywords:  BE; CRISPR-Cas9 technology; DNA.; PE; Sickle cell disease; beta globin; clinical trials; patents
    DOI:  https://doi.org/10.2174/0113892002356293250225094826
  4. Br J Haematol. 2025 Mar 03.
    A young adult clinic to support integration into adult sickle cell disease care: If you build it, they will come.
    Elizabeth J Prince, Jayla L Scott, Ogechi Nwankwoala, Lystra Ali-Houchens, M Amir Alghali, C Patrick Carroll, Sophie Lanzkron, Lydia H Pecker.
      In high-income countries, individuals with sickle cell disease (SCD) almost universally survive into adulthood, but transfer to adult SCD care is fraught. The young adult clinic (YAC) at our sickle cell centre was designed to provide developmentally appropriate, expert SCD care to young adults with SCD aged 18-30 years. In this retrospective cohort study, we measured YAC appointment attendance and scheduling attempts based on patient referral source and demographic characteristics. Between 1 March 2019 and 30 September 2023, 89% (170/192) of referred patients attended a YAC appointment, and 97% (77/79) of patients referred from paediatric SCD care attended a YAC appointment. Most patients attended their first scheduled appointment (61%, 105/170). Among rescheduled patients, the mean number of scheduling attempts before attendance was 2.9 (standard deviation 1.5). During the 55-month study period, this cohort had five deaths (3%) and seven successful haematopoietic stem cell transplants (4%). These results indicate that healthcare systems designed to meet the needs of young adults with SCD enable successful participation in adult SCD care. Resources to build robust adult SCD care systems are desperately needed, alongside research regarding optimal approaches to integrating young people into adult SCD care.
    Keywords:  care transitions; emerging adulthood; sickle cell disease
    DOI:  https://doi.org/10.1111/bjh.20032
  5. Prostaglandins Leukot Essent Fatty Acids. 2025 Feb 24. pii: S0952-3278(25)00007-9. [Epub ahead of print]205 102670
    Plasma oxylipins in children with sickle cell disease: Associations with biomarkers of inflammation and endothelial activation.
    Bn Yamaja Setty, Krishna Rao Maddipati, Scott W Keith, Ayako Shimada, Pari Sheerer, Robin E Miller.
      Oxylipins are polyunsaturated fatty acid (PUFA)-derived inflammatory mediators, and include both pro-inflammatory (prostaglandins, thromboxane, leukotrienes), and pro-resolving (lipoxins, E-resolvins, D-resolvins, protectins, maresins) molecules. Sickle cell disease (SCD) is an inflammatory pathology. We profiled plasma oxylipins in SCD (n = 45) and control children (n = 24), and evaluated their associations with inflammatory biomarkers, and SCD clinical history. We demonstrated the presence of PGE2, TxB2, RvE2, RvD1, AT-RvD3, and numerous monohydroxy-PUFAs in both SCD and control plasma. Levels of TxB2, RvD1, 12-HETE, 5-HEPE, and 7-HDoHE were significantly increased in SCD. 12-HETE and 5-HEPE correlated positively with IL-6 and IL-1β, respectively, while 15-HETE negatively associated with soluble-ICAM-1. 7-HDoHE levels were significantly lower in children with a history of VOC and ACS compared to those without any clinical complications. Since RvD1 is a pro-resolving mediator, the observed increase in RvD1 in SCD may reflect a host mechanism attempting to mitigate disease-associated chronic inflammation by promoting resolution of inflammation.
    Keywords:  Biomarkers of endothelial activation; Biomarkers of inflammation; Oxylipins; Resolvins; Sickle cell disease; Specialized pro-resolving lipid mediators
    DOI:  https://doi.org/10.1016/j.plefa.2025.102670
  6. Hemoglobin. 2025 Mar 05. 1-9
    Haplotype-Specific Genetic Epidemiology of Sickle Cell Anemia Patients in Accra, Ghana: Patterns, Clinical Implications, and Public Health Responses.
    Francis Abeku Ussher, Edwin Ferguson Laing, Ernest Kissi Kontor, Alex Bismark Atta-Owusu, Nityanand Jain, Robert Amadu Ngala, Shadrach Coffie Asiedu.
      Sickle cell disease (SCD) is a genetic disorder with a diverse spectrum of clinical presentation, often determined by inherited βS gene haplotypes. Ghana, a country with a significant SCD burden, lacks population haplotype frequency data, hindering anthropological, genetic, and clinical understanding and management of the disease. A prospective sample of 191 SCD patients (sickle cell anemia; homozygous HbSS) was recruited at the Korle-Bu Teaching Hospital, Accra. Identification of βS gene haplotypes was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Hematological tests were performed using routine laboratory procedures. Kruskal-Wallis ANOVA with Dunn post-hoc was used to compare the hematological parameters. Multinomial probability models were used to compare the frequencies of the observed haplotypes with those reported in other African countries. The Atypical haplotype was disproportionately prevalent (58%), followed by the Bantu/CAR (20%) and Benin (10%) haplotypes. Significant differences were observed between the haplotypes in lymphocyte count, platelet count, sodium and potassium levels (P < 0.001). In addition, disease severity varied significantly between haplotypes (P = 0.010), with notable differences between the Atypical and Bantu/CAR haplotypes (PFDR = 0.020). Multinomial probability testing revealed a substantial deviation from the expected haplotype distribution, highlighting significant differences in haplotype frequencies between Ghana and other African countries. The Wright-Fisher model showed that the variation in Arab-Indian haplotype frequency reached zero by the 100th generation. Our findings highlight the need to study haplotype composition in Ghana to identify population-specific risk factors and tailor public health interventions to better manage patient needs.
    Keywords:  Ghana; Sickle cell disease; disease severity; epidemiology; haplotypes
    DOI:  https://doi.org/10.1080/03630269.2025.2474609
  7. Nat Commun. 2025 Mar 01. 16(1): 2092
    FLT1 and other candidate fetal haemoglobin modifying loci in sickle cell disease in African ancestries.
    Ambroise Wonkam, Kevin Esoh, Rachel M Levine, Valentina Josiane Ngo Bitoungui, Khuthala Mnika, Nikitha Nimmagadda, Erin A D Dempsey, Siana Nkya, Raphael Z Sangeda, Victoria Nembaware, Jack Morrice, Fujr Osman, Michael A Beer, Julie Makani, Nicola Mulder, Guillaume Lettre, Martin H Steinberg, Rachel Latanich, James F Casella, Daiana Drehmer, Dan E Arking, Emile R Chimusa, Jonathan S Yen, Gregory A Newby, Stylianos E Antonarakis.
      Known fetal haemoglobin (HbF)-modulating loci explain 10-24% variation of HbF level in Africans with Sickle Cell Disease (SCD), compared to 50% among Europeans. Here, we report fourteen candidate loci from a genome-wide association study (GWAS) of HbF level in patients with SCD from Cameroon, Tanzania, and the United States of America. We present results of cell-based experiments for FLT1 candidate, demonstrating expression in early haematopoiesis and a possible involvement in hypoxia associated HbF induction. Our study employed genotyping arrays that capture a broad range of African and non-African genetic variation and replicated known loci (BCL11A and HBS1L-MYB). We estimated the heritability of HbF level in SCD at 94%, higher than estimated in unselected Europeans, and suggesting a robust capture of HbF-associated loci by these arrays. Our approach, which involved genotype imputation against six reference haplotype panels and association analysis with each of the panels, proved superior over selecting a best-performing panel, evidenced by a substantial proportion of panel-specific (up to 18%) and a low proportion of shared (28%) imputed variants across the panels.
    DOI:  https://doi.org/10.1038/s41467-025-57413-5
  8. J Pediatr Hematol Oncol. 2025 Mar 03.
    Hereditary Pyropoikilocytosis as a Modifier of Sickle Cell Disease Severity.
    Megan Lantz, Lily Dolatshahi.
      Mutations that alter the structure of red blood cells, including the mutations that cause sickle cell disease (SCD), are common globally because they protect against malaria. Patients with SCD rarely develop severe anemia that requires blood transfusions before 6 months of age. We present the case of a patient with SCD who developed severe anemia requiring a blood transfusion at 6 weeks old and subsequent transfusions throughout her first two and a half years of life. Next-generation sequencing genetic testing revealed that the patient also had hereditary pyropoikilocytosis (HPP), a severe form of hereditary elliptocytosis (HE), and was heterozygous for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Following splenectomy, the frequency of her transfusions slightly decreased. This case demonstrates that HPP modifies the severity of SCD and highlights the importance of considering additional hematologic conditions and obtaining genetic testing in patients with SCD and early-onset anemia.
    DOI:  https://doi.org/10.1097/MPH.0000000000003012
  9. J Sick Cell Dis. 2025 ;2(1): yoaf003
    Nocturnal hemoglobin desaturation in chronically transfused adults with sickle cell disease: a retrospective study.
    Mofiyin A Obadina, Iman Owens, Ada Chang, Vanessa Miller, Jane A Little.
      High-risk SCD may be managed with chronic red blood cell exchange transfusions. We examined the prevalence of sleep-associated hypoxemia (≥5 minutes at SpO2 ≤88%) or nocturnal Hb desaturation (NHD) in chronically transfused adults with SCD. Of 41 identified participants, 15 (36.6%) had tested positive for NHD at some point prior to enrollment. The median duration of desaturation (SpO2 ≤88%) in those that tested positive was 88.3 minutes (IQR 27.9-226.0 minutes). Participants with and without NHD were compared using non-parametric statistical tests. Compared to participants without NHD, those with NHD had higher absolute reticulocyte counts (P = .018) and white blood counts (P = .05) and tended to be older. They had more anemia (P = .11) and higher lactate dehydrogenase levels (P = .072). Older age at initiation of chronic red blood cell transfusions associated the strongest with a longer duration of NHD (ρ = 0.4253, P = .0067), while prior history of cerebrovascular events associated with a shorter duration of NHD (P = .0315). Our results demonstrate that NHD is common in adults being treated with red blood cell exchange for high-risk SCD and associates with laboratory evidence of increased disease activity. Increased awareness of this complication and appropriate screening may provide an additional simple, low-cost, and physiologically relevant treatment intervention, that is oxygen therapy.
    Keywords:  SCD; chronic transfusion; hypoxemia; nocturnal Hb desaturation; sleep disorder
    DOI:  https://doi.org/10.1093/jscdis/yoaf003
  10. J Postgrad Med. 2025 Mar 06.
    Assessing and managing iron deficiency anemia in sickle cell disease: Insights from a systematic review and meta-analysis.
    A Jose, A Bodade, M R Madkaikar.
       ABSTRACT: Sickle cell disease (SCD) is prevalent in Sub-Saharan Africa, the Middle East, and parts of India, where it is often complicated by iron deficiency anemia (IDA). Untreated IDA exacerbates SCD symptoms, reducing quality of life (QOL) and increasing morbidity and mortality. Diagnosis typically depends on ferritin levels, which can be unreliable due to inflammation associated with SCD's altered red cell morphology and chronic hemolysis. This systematic review and meta-analysis explores the interplay between IDA and SCD, focusing on diagnostic criteria for effective management. We conducted a thorough search of PubMed and EMBASE, leading to the selection of 14 studies following PRISMA guidelines. The review protocol was registered in PROSPERO (CRD42023462914). Data extraction, quality assessments, and heterogeneity checks were rigorously performed. Out of 3188 articles, 14 studies met the inclusion criteria, covering 763 SCD cases with 118 instances of IDA. The meta-analysis found an IDA prevalence of 6% (95% CI: 1%-20%) among SCD patients, with high heterogeneity (I2 = 88.8%). Sensitivity analysis adjusted for publication bias indicated an 8% prevalence (95% CI: 4%-19%) with reduced heterogeneity (I2 = 19.5%). Subgroup analysis revealed a lower prevalence of IDA in pregnant women (0.01%; 95% CI: 0.00%-0.92%) compared to non-pregnant individuals (7%; 95% CI: 2%-22%). The study highlights significant regional variability in IDA prevalence among SCD patients, emphasizing the importance of early diagnosis and targeted management to improve patient outcomes and QOL.
    DOI:  https://doi.org/10.4103/jpgm.jpgm_590_24
  11. BMC Emerg Med. 2025 Mar 01. 25(1): 33
    Factors associated with early return visits to the emergency department in patients with vaso-occlusive crisis.
    Mohammed Khalid Alageel, Hassan Mohammad Aloraini, Alanoud Mansour Alessa, Alanoud Binmethem, Ghada Alsaleh, Sarah Abdullah Almubrik, Abdulaziz Alalshaikh, Kholood K Altassan.
       BACKGROUND AND AIM: One of the most common presentations of sickle cell disease (SCD) in the emergency department (ED) is acute severe pain episodes due to a vaso-occlusive crisis (VOC). Management of these episodes is primarily through intravenous pain control, but patients often return to the ED with the same complaint a few days after discharge. While some global studies have explored the risk factors for ED revisits due to VOC, the literature is lacking in the adult population, specifically in Saudi Arabia where SCD prevalence is high. The goal of this study is to measure the incidence of ED 72-hour early revisit (ERV) among SCD patients due to a VOC episode and to identify factors that might be associated with an ERV in this population. We conducted a retrospective cohort study using the electronic medical records, retrieving all patients who presented to the ED with a VOC from the period of 2017 to 2022.
    RESULTS: This study included 120 VOC visits. The percentage of 72-hour ERV to the ED among VOC patients was 39.2%, in which 91.5% received opioids, and 31.9% were admitted during the return visit. Return visitors' median age was 29, most of them were male. There was no statistically significant correlation found between the patients' 72-hour ERV to the ED and their age, gender, comorbidities, history of exchange transfusion, pain score, or dose of opiates received. Of the variables measured at the index visit only the direct bilirubin level, and time to first opioid dose was associated with 72-hour ERV with an OR of 1.08 (95%CI: 1.0 to 1.16, P = 0.022) and 0.99 (95%CI: 0.99 to 0.99, P = 0.012) respectively.
    CONCLUSION: We found that 39.2% of VOC episodes discharged from the ED had an ERV. This rate is higher than what is reported internationally. Additionally, the lack of clear predictors for revisits raises doubts regarding the efficacy of the ED ''treat and release'' approach in this population.
    CLINICAL TRIAL NUMBER: Not applicable.
    Keywords:  Early return visit; Emergency department; Hemoglobinopathy; Saudi Arabia; Sickle cell disease; Vaso-occlusive crisis
    DOI:  https://doi.org/10.1186/s12873-025-01192-1
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