bims-sicedi 2025-11-16 papers

Obstet Med. 2025 Nov 10. 1753495X251391574

Management of sickle cell disease in pregnancy.

Tabea Sutter, Nadine Shehata, Kristine Matusiak, A Kinga Malinowski.

Sickle cell disease (SCD) is the most common hemoglobinopathy, characterized by hemolysis and vaso-occlusion, resulting in multisystem disease. Pregnant patients with SCD may have preexisting organ dysfunction and SCD-specific pregnancy complications. Risk for adverse maternal or fetal outcomes is significantly elevated in SCD patients, and multidisciplinary care in a center with expertise is essential to minimize complications.

Keywords: Sickle cell disease; hydroxyurea; pregnancy; pregnancy complications; vaso-occlusion

DOI: https://doi.org/10.1177/1753495X251391574

Biomarkers. 2025 Nov 09. 1-11

Association of Cell Adhesion Molecules with Vaso-occlusive crisis in Sickle Cell Disease.

Parul Gupta, Brajesh Patel, Asha Tiwari, Pankaj Asati, Ravindra Kumar.

ObjectiveThe aim of this study is to see the association of P-selectin, E-selectin, Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intercellular Adhesion Molecule-1 (ICAM-1) with Vaso-occlusive crisis (VOC) in sickle cell disease patients.MethodsIn this longitudinal study, a total of 140 SCD patients admitted into a Government Medical College, Jabalpur, were recruited . Plasma levels of soluble P-selectin, E-Selectin, ICAM-1, and VCAM-1 were measured at three different time points, that is, (i) at the time of admission (n = 140), (ii) at discharge (n = 139), and (iii) during steady state (n = 118).ResultsThe most common presenting symptoms at the time of VOC were severe joint pain (65.7%) and back pain (49.3%). All the cell adhesion molecule levels were similar in males and females except sVCAM-1. The plasma P-selectin, E-Selectin, ICAM-1 and VCAM-1 levels were significantly higher during crisis than at the discharge and steady state . No statistically significant association of any of the CAM levels with the severity of pain was observed. High plasma VCAM-1 levels (≥1676 ng/mL) were associated with longer duration of hospital stay.ConclusionsSignificant association of soluble CAMs with VOC in SCD suggests that soluble CAMs play a crucial role in the pathophysiology of the VOC.

Keywords: Cell Adhesion Molecules; Endothelium; Sickle cell disease; Vaso-Occlusive Crisis

DOI: https://doi.org/10.1080/1354750X.2025.2586746

Pediatr Clin North Am. 2026 Feb;pii: S0031-3955(25)00109-9. [Epub ahead of print]73(1): 29-41

Hydroxyurea for Children with Sickle Cell Disease: A Practical Guide for Pediatric Clinicians.

Francis Coyne, John J Strouse.

Hydroxyurea is the cornerstone therapy for children with sickle cell disease (SCD). Children with sickle cell anemia (SCA; ∼64% of children with SCD) should be started on hydroxyurea as infants and continue treatment throughout childhood. Hydroxyurea reduces acute complications and chronic organ injury in children with SCA. Hydroxyurea may reduce acute complications in children with HbSC and HbSß+ with frequent complications, but the evidence is limited. We recommend a close partnership between the primary care pediatric clinicians and a sickle cell specialist to reduce barriers to starting and maintaining adherence to hydroxyurea.

Keywords: Guidelines; Hydroxyurea; Pediatric; Sickle cell anemia; Sickle cell disease

DOI: https://doi.org/10.1016/j.pcl.2025.08.007

Pediatr Clin North Am. 2026 Feb;pii: S0031-3955(25)00123-3. [Epub ahead of print]73(1): xvii-xviii

The Pediatric Clinician's Expanding Role in Sickle Cell Disease.

Michael Rutledge DeBaun.

DOI: https://doi.org/10.1016/j.pcl.2025.09.002

Int J Mol Sci. 2025 Oct 28. pii: 10458. [Epub ahead of print]26(21):

Pleiotropic Effects of Polymorphisms in the BCL11A Gene on Laboratory Parameters in Sickle Cell Anemia.

Antonio Mateus Oliveira, Luciana Fiuza, Camylla Figueiredo, Caroline Guarda, Rayra Santiago, Sètondji Yahouédéhou, Suéllen Carvalho, Ana Paula Pacheco, Isa Lyra, Elisângela Vitória Adorno, Cynara Barbosa, Marilda Gonçalves.

Sickle cell anemia (SCA) is characterized by hematological events that lead to vaso-occlusion and the onset of clinical manifestations. Fetal hemoglobin (HbF) has been shown to positively influence the clinical outcomes of individuals with SCA. Genetic polymorphisms are known to modulate clinical phenotypes by increasing HbF levels, with the BCL11A gene being an important marker in this regard for future therapies. However, while the BCL11A gene plays a role in the regulation of several genes during hematopoiesis, its various effects are not yet fully understood. The study aimed to investigate association between laboratory biomarkers in the presence of rs766432 and rs6732518 polymorphisms in the BCL11A gene. Hematological and biochemical markers were analyzed using automated methods, while genetic markers were identified by PCR-RFLP techniques. Elevated HbF levels were significantly associated with the presence of rs766432 and rs6732518 polymorphisms. High concentrations of HDL were associated with rs766432 polymorphism, and elevated levels of alpha-1antitrypsin were linked to the rs6732518 polymorphism. No correlation was found between HbF and HDL concentrations. The low sample size represents a major constraint, making the results only suggestive. In conclusion, polymorphisms in the BCL11A gene are important for variations in HbF levels and may have a pleiotropic effect by influencing laboratory parameters unrelated to HbF levels.

Keywords: A1AT; BCL11A polymorphism; HDL; fetal hemoglobin; sickle cell anemia

DOI: https://doi.org/10.3390/ijms262110458

PLoS One. 2025 ;20(11): e0336567

Early risk factors for acute chest syndrome in sickle cell anemia: A pediatric study.

Mohamed Condé, Florie Bouvier, Roselyne Brat, Salim Ferrani, Régis Hankard, Philippe Connes, Georges Dimitrov.

Acute chest syndrome (ACS) is a life-threatening complication of sickle cell anemia (SCA). Most often, ACS occurs during the progression of a painful vaso-occlusive crisis (VOC) in vulnerable patients. The present study aimed to identify early risk factors for ACS progression, focusing on patient assessments in a pediatric Emergency Department. In this study (2016-2022) concerning exclusively the SS and Sβ0 sickle cell disease genotypes, severe VOC encounters progressing to ACS were compared to uncomplicated severe VOCs. Medical history, clinical and laboratory data were collected for both groups. Out of 280 severe VOC encounters without initial respiratory symptoms, 40 progressed to life-threatening acute chest syndrome. The forty ACS (age 8.5 ± 4.3 years, 37% females) were compared with 240 severe VOCs (9.3 ± 4.4 years, 46% females). ACS was positively correlated with the occurrence of VOC at night, diffuse (multifocal) pain and increased C-Reactive protein (p < 0.05). The multivariable modelling, using generalized linear mixed-effects models, defined three risk factors for ACS occurrence: diffuse pain, night-time pain occurrence, and increased C-Reactive protein (p < 0.01). Increased use of opiates in the Emergency Department, elevated total leucocyte count, breath rate, and decreased red blood cell count were not significantly associated with ACS occurrence (p > 0.05). The initial evaluation of SCA patients' acute pain in the Emergency Department is crucial for subsequent management during hospitalization.

DOI: https://doi.org/10.1371/journal.pone.0336567

Cureus. 2025 Oct;17(10): e94286

Clinical and Microbiological Profile of Infections in Hospitalized Patients with Sickle Cell Disease: A Tertiary Care Centre Experience from Central India.

Ananta Mishra, Pankaj K Kannauje, Vinay Pandit.

Background Sickle cell disease (SCD) is highly prevalent among India's tribal populations, with infections being a major cause of morbidity and mortality. Current data on causative pathogens, antimicrobial resistance patterns, and clinical predictors of outcomes in Indian SCD patients remain limited. This study aims to characterize the clinical and microbiological profile of infections in hospitalized SCD patients and identify predictors of adverse outcomes. Methods An ambispective observational study was conducted at a tertiary care center in central India from December 2018 to December 2021 (retrospective phase, n=61) and January 2022 to June 2023 (prospective phase, n=150), totaling 211 SCD patients with confirmed infections. Data were analyzed using IBM SPSS Statistics software, version 25.0 (IBM Corp., Armonk, NY). An exploratory secondary analysis developed a preliminary risk score for predicting adverse outcomes using multivariate logistic regression and receiver operating characteristic (ROC) curve analysis. Results Among 211 hospitalized SCD patients (median age 21 years, range two to 65 years), respiratory infections were most common (34.6%), followed by acute undifferentiated febrile illness (19.9%), bone and joint infections (9.5%), and bloodstream infections (9%). Among 32 gram-negative isolates, 50% were extended-spectrum β-lactamase (ESBL) producers with 100% susceptibility to polymyxins. Fever was present in 86.7% of patients. Procalcitonin levels >2 ng/mL were significantly associated with adverse outcomes (p=0.04). Overall mortality was 6.6% (14 deaths), with respiratory infections accounting for the highest number of deaths (8/73, 11.0%). An exploratory SCD Infection Risk Score (SCD-IRS) incorporating age, hemoglobin level, total leucocyte count, and procalcitonin demonstrated moderate discriminative ability with an area under the curve (AUC) of 0.78 (95% CI: 0.65-0.91, p<0.001) but lacks internal validation due to sample size constraints. Conclusions Respiratory infections predominate among hospitalized SCD patients in central India. High antimicrobial resistance poses significant treatment challenges. Elevated procalcitonin levels (>2 ng/mL) are significantly associated with adverse outcomes. The preliminary SCD-IRS shows potential for risk stratification but is strictly exploratory and requires validation in larger, multi-institutional studies before any clinical application. Strengthening vaccination coverage, implementing antimicrobial stewardship programs, and developing validated risk assessment tools are essential to reduce infection-related morbidity and mortality in this vulnerable population.

Keywords: antimicrobial resistance; infections; procalcitonin; risk score; sickle cell disease; tribal population

DOI: https://doi.org/10.7759/cureus.94286

Gates Open Res. 2025 ;9 101

CYP2D6 Pharmacogenetics in Nigerian Sickle Cell Disease: Phase 1 of Implementing Pharmacogenomics Testing for Effective Care and Treatment in Africa (iPROTECTA) program.

Consortium for Genomics and Therapeutics in Africa

Background: Sickle Cell Disease (SCD) is highly prevalent in Nigeria, with severe pain crises being a primary cause of morbidity. Codeine and tramadol are frequently used opioids, but their effectiveness and safety are significantly influenced by CYP2D6 genetic variations. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines exist for opioid therapy based on CYP2D6 phenotypes. There's a critical need for pre-emptive pharmacogenomic (PGx) testing in African SCD patients to guide opioid selection. This study aimed to determine CYP2D6 allele, phenotype frequencies and evaluate the feasibility of implementing pre-emptive pharmacogenomic (PGx) testing to guide opioid therapy for SCD patients in Nigeria.
Methods: This prospective, multicenter implementation study recruited 503 consenting SCD patients (HbSS or HbSC) aged ≥15 years from five Nigerian sites. Blood samples were collected for DNA extraction. CYP2D6 single-nucleotide polymorphisms and copy number variations were determined using Taqman assays based open array, GenoPharm. Phenotypes were assigned based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines using the Genomics Information Management System (GIMS). and patient-specific medication safety cards were generated.
Results: We successfully genotyped 503 SCD patients with a mean age of 25.1 years, while 61.4% were female, and hydroxyurea use was less than 9.4%. Actionable CYP2D6 variants were found in 36.6% of participants. The predicted phenotype distribution was 8.8% Ultrarapid Metabolizers (UM), 54.1% Normal Metabolizers (NM), 26.0% Intermediate Metabolizers (IM), and 1.8% Poor Metabolizers (PM), with 9.3% undetermined. Patient medication safety cards were provided to guide prescriptions.
Conclusions: This study successfully established a genotyped cohort of 503 Nigerian SCD patients, demonstrating the feasibility of pre-emptive pharmacogenetic testing through a Pan-African collaborative model in a resource-limited setting. The identification of PM and UM provides direct clinical guidance, as CPIC guidelines recommend avoiding codeine and tramadol in these groups due to the high risk of diminished efficacy or serious toxicity, respectively. The high prevalence of actionable CYP2D6 variants indicates a substantial proportion of Nigerian SCD patients may experience altered opioid responses, underscoring the need for tailored prescribing to optimise pain control and minimise adverse drug reactions.

Keywords: CYP2D6; Sickle Cell Disease; genotype; opioids; phenotype; pre-emptive pharmacogenomic

DOI: https://doi.org/10.12688/gatesopenres.16370.1