bims-sicedi 2026-02-01 papers

Hemoglobin. 2026 Jan 28. 1-10

Identification of Sickle Cell Disease and Its Associated Other Structural Variants of Hemoglobin Using High Performance Liquid Chromatography and Their Clinical Profiling.

Dhirendra Kumar, Lokeswara Bala Krishna S, Sridevi Parikipandla.

Sickle cell disease (SCD), a well known hemoglobinopathy, is a recessive inherited blood abnormality caused by point mutation in hemoglobin proteins, notably prevalent in the tribal belt of Madhya Pradesh, India. The study aims to identify the SCD-associated hemoglobinopathies related to α- and β-globin structural variants. Over 1,200 symptomatically positive SCD individuals were screened and 503 solubility test positive samples were identified and further complete blood count (CBC) analysis showed 382 participants with abnormal hemoglobins. Confirmatory tests were alkaline electrophoresis on cellulose acetate membrane and high performance liquid chromatography (HPLC). Our study identified Hb variants, including HbSS (21.26%), HbSF (11.39%), and HbAS (63.73%). Other prevalent variants are HbJ, Hb D-Punjab, and Hb Lepore. Moreover, based on the HPLC retention time, 99 β-variants, 115 α-variants, 12 tetramers, and eight δβ-hybrid Hb variants, with six samples serving as a control for comparative analysis. Additionally, clinical profiling showed that severities are increased in combination with HbS along with other hemoglobinopathies. Further, the study reveals that Hb variants are prevalent in females, between age group of 21-30 years showing highest frequency of SCD. This study emphasizes the effectiveness of complete hemoglobinopathy screening and clinical profiling for measuring the normal and pathological conditions of the sickle cell patients.

Keywords: Sickle cell disease; clinical profiling; hemoglobin variants; hemoglobinopathies; high performance liquid chromatography (HPLC)

DOI: https://doi.org/10.1080/03630269.2025.2590259

Am J Hematol. 2026 Jan 28.

Vascular Geometry Drives Stroke Risk in Sickle Cell Disease.

Weiqiang Liu, Christian Kassasseya, Lazaros Papamanolis, Kim-Anh Nguyen-Peyre, Morgane Garreau, Saskia Eckert, Gonzalo De Luna, Thomas d'Humières, Vincent de Pierrefeu, Cecile Arnaud, Nour Bekeziz, Marie Pierre Gobin Metteil, Corentin Provost, Jean-Frédéric Gerbeau, Suzanne Verlhac, Pablo Bartolucci, Irene Vignon-Clementel.

Sickle cell disease (SCD) is the leading cause of stroke in children and young adults, primarily due to cerebral vasculopathy (CV) occurring within the first decade of life. The main risk factor for CV is elevated blood velocity in intracranial arteries, contributing to stenosis formation in very young children. This study addresses three key questions: (i) the relationship between hemoglobin levels and intracranial blood velocities in SCD patients, (ii) additional factors contributing to elevated velocity beyond anemia, and (iii) the presence of flow anomalies. To investigate these aspects, biological and transcranial Doppler data from pediatric and adult SCD patients were analyzed. An image-based in silico modeling approach was also developed to simulate blood flow in the internal carotid, anterior cerebral, and middle cerebral arteries of SCD patients, of different age classes, and prior to any possible stenosis. Analysis revealed that while anemia is a recognized CV risk factor, it does not fully explain elevated velocities, as no significant correlation was found in children under five. In in silico simulations, young patients reached pathological arterial intracranial velocities at physiological flow rates, whereas adults remained below risk thresholds even at high flow rates. Pathological velocities were primarily observed in distal internal carotid arteries, where stenoses often develop. High flow rates, small arterial diameters, and pronounced curvatures led to extreme velocities and complex flow, likely causing endothelial damage and promoting CV progression. These findings enhance understanding of hemodynamic mechanisms underlying SCD-related stroke risk, paving the way for improved predictive models and early interventions. Trial Registration: ClinicalTrials.gov identifier: NCT05199766.

Keywords: cerebral hemodynamics; cerebral vasculopathy; computational modeling; sickle cell disease; stroke risk; vascular geometry

DOI: https://doi.org/10.1002/ajh.70184

Adv Healthc Mater. 2026 Jan 29. e04346

Hemoglobin as a Molecular Glue: Toward Potent Inhibition of HbS Polymerization in Sickle Cell Disease.

Mohammad Edrisi, Navid Rabiee.

Sickle cell disease (SCD), a monogenic disorder arising from a single point mutation in the β-globin gene, continues to pose a significant global health burden despite advances in supportive care. This mutation drives the formation of hemoglobin S (HbS) polymers under deoxygenated conditions, causing erythrocyte sickling, vaso-occlusive crises, and multi-organ complications. Current therapies, such as hydroxyurea and voxelotor, provide only partial symptomatic relief, underscoring the urgent need for transformative strategies. This review highlights the molecular glue paradigm, a novel approach that repurposes hemoglobin itself as a therapeutic scaffold. By integrating high-resolution structural insights from cryo-electron microscopy and predictive modeling via artificial intelligence, engineered hemoglobin variants can be rationally designed to inhibit polymerization, stabilizing non-pathogenic conformations and preventing fiber formation. These molecular glues, generated through gene editing or synthetic biology, offer a cell-intrinsic, high-concentration mechanism to counteract HbS polymerization, potentially overcoming the limitations of current therapies. We examine the key challenges in translating this paradigm, including precise structural characterization of polymerization intermediates, efficient intracellular delivery to erythrocytes, temporal regulation under hypoxic conditions, and the mitigation of immunogenicity.

Keywords: hemoglobin; molecular glue; molecular pathogenesis; sickle cell disease

DOI: https://doi.org/10.1002/adhm.202504346

Pediatr Emerg Care. 2026 Jan 29.

Frank Gonzalez, Matt Hall, Rima Habre, Jay G Berry, Yan Xu, Danica B Liberman, Pradip P Chaudhari.

OBJECTIVE: Sickle cell disease (SCD) is an inherited disorder that leads to significant morbidity from health complications beginning in childhood. Weather-related factors may influence the frequency of SCD complications, but evidence regarding the impact of weather changes in the pediatric population remains limited. Our objective was to determine the association between weather-related exposures and odds of emergency department (ED) visits for acute complications in youth with SCD.
METHODS: We conducted a retrospective case-crossover study of ED encounters among patients aged 0 to 21 years at 40 US children's hospitals (2015-2020). ED visits for vaso-occlusive crisis (VOC) and/or acute chest syndrome (ACS) were included. Patients were categorized as low-risk or high risk based on the number of ED visits in the preceding year. We constructed single-variable conditional logistic regression models to identify the odds of ED visit in association with weather-related exposures of temperature, heat index (HI), and wet bulb globe temperature (WBGT).
RESULTS: Among 48,885 ED encounters for VOC and ACS in high-risk patients, increases in temperature, HI, and WBGT on lag day 3 were associated with increased odds of ED visits for VOC. Increases in these variables were associated with decreased odds of ED visits for ACS. No significant associations were found for low-risk patients.
CONCLUSIONS: Increased temperature, HI, and WBGT among high-risk pediatric patients with SCD were associated with increased odds of ED visit for VOC and decreased odds for ACS. As climate change progresses, further studies are needed to identify population, neighborhood, and patient-level environmental risk factors contributing to acute complications for patients with SCD.

Keywords: climate change; heat stress; meteorological; sickle cell disease

DOI: https://doi.org/10.1097/PEC.0000000000003561

Medicina (Kaunas). 2026 Jan 15. pii: 172. [Epub ahead of print]62(1):

Pharmacogenomics and Opioid Efficacy in Sickle Cell Disease.

Rabab H Elshaikh, Asaad M Babker, Sanaa Elfatih Hussein, Khalid Abdelsamea Mohamed Ahmed, Ashok Kumar Sah, Ayman Hussein Alfeel.

The impact of genetic variation in sickle cell patients plays a significant role in opioid therapy individual response and pain management. This review aims to provide a comprehensive overview of the importance of exploring genetic variability and its impact on pain management in patients with sickle cell disease. It also explores opioid therapy variability and opioid Safety. With respect to literature, the polymorphisms in the key metabolic enzymes CYP2D6, UGT2B7, and COMT, as well as variations in the OPRM1, are important modifiers of the pharmacokinetics and pharmacodynamics of opioids. Variations in the COMT gene can influence how the body manages certain brain chemicals and how pain is experienced, while changes in the OPRM1 gene can alter how well opioids bind to their receptors. They help determine how opioids are broken down in the body, how well they attach to pain receptors, and how pain is felt by someone with sickle cell disease. Patients with reduced-function and ultra-rapid CYP2D6 alleles have a modified metabolism of codeine and tramadol, which presents either a reduced analgesic response or a risk for increased toxicity. These observations support the case for the need for tailored opioid prescriptions in a population that is genetically diverse, as well as the risk of not having standardized pain measurement, and the absence of clinical implementation. There remains the risk of unrecognized pharmacogenomics, lack of data, and personalized opioid descriptions persist. Future research should focus on integrating genetic testing into clinical practice to optimize opioid selection, personalize medicine, minimize adverse effects, and ensure each patient receives treatment that is both effective and safe to enhance quality of life for individuals with sickle cell disease.

Keywords: genetic variants; opioid efficacy; pain management; pharmacogenomics; sickle cell disease

DOI: https://doi.org/10.3390/medicina62010172