Sickle cell disease in europe: A cross-border real-world data analysis from the radeep registry
Year: 2025
Type: conference-abstract
Abstract: Introduction Advances in understanding the pathophysiology and clinical heterogeneity of sickle cell disease (SCD) have led to new therapies and patient stratification. However, limited availability of cross-border standardized data and insufficient integration into health policy frameworks hinder personalized care. We present the first European dataset of SCD patients captured in the RADeep Registry, endorsed by the European Hematology Association, from 2019-12-01 to 2024-11-30. The aim is to characterize disease burden, clinical outcomes, acute events, organ damage, treatment patterns, and healthcare resource utilization. Methods Patient individual data (PID) were collected prospectively and longitudinally from healthcare centers in RADeep-participating EU countries. Patients with prior successful stem cell transplantation or gene therapy were excluded. Analyses were stratified by age group (pediatric <18 years vs adult), subdiagnosis (SCA vs SC), and genotype (SS, Sβ⁰, SC, Sβ⁺). Results Standardized PID was collected on 3119 SCD patients across 80 centers in 7 countries (Belgium, 14; Denmark, 1; France, 2; Greece, 1; Italy, 25; The Netherlands,4; and Spain, 33). The cohort was gender-balanced (52.5% female), with a median age of 14 years (62.1% pediatric), though only 41.3% were diagnosed via neonatal screening. Subdiagnosis distribution: 71.6% (2233) SCA; 15% (466) SC; 10.9% (339) Sβ thalassemia and 2.5% (79) S associated with another hemoglobin anomaly. Confirmatory genotype was available for 1003 patients (32.1%). Two or more painful vaso-occlusive crises in the past 12 months were reported by 7% of patients (adults 9.9%, pediatrics 5.1%). When considering all vaso-occlusive events including painful crises, cerebrovascular events (e.g., stroke, TIA), thoracic/abdominal organ involvement (e.g., ACS, hepatic/splenic sequestration), thrombotic episodes, and ischemia-related infections, the proportions were similar (13.3%, 12.1%). At least one chronic organ damage manifestation (cardiac/pulmonary, neurological, endocrine, liver/kidney, visual/hearing) was reported in 71.6% of adults (SCA 75.4%, SC 74.7%) and 21.6% of pediatric patients (SCA 24%, SC 16.1%). The most reported complications in SCA and SC were retinopathy (RET) and avascular necrosis (AN). RET affected 39.9% of adults (SCA 42.1%, SC 56.9%) while only 2.8% of pediatric patients (SCA 2.1%, SC 5.9%). AN was reported in 24.1% of adults (25.8% SCA, 20% SC) and only in 3% of pediatric patients. Renal manifestations included microalbuminuria, reported in 10.7% of adults (SCA 13.8% SCA, SC 4.4%) and renal insufficiency, reported in 7.6% of adults (9.6% SCA, 1.3% SC). None was substantially reported in the pediatric cohort. Pulmonary hypertension was reported in 10.2% of adults and 4.3% of pediatric patients. Notably, acute and chronic complications were higher in SCA compared to SS-confirmed genotype patients, suggesting that the SCA subdiagnosis includes a heterogeneous subgroup (SB0 or SδB0 thalassemia) with different clinical phenotypes. Hydroxyurea was prescribed to 72.1% of patients (83.4% SCA vs 27.5% SC), with no age cohort differences in SCA. However, in SC, higher rates were reported for adults (31.3% vs 25.5%). Splenectomy was performed in 7.3% of the patients. The main indication was recurrent splenic sequestration (59.6%) followed by hypersplenism (21.9%). Overall, 8.1% of all SCD patients (SCA 8.5%, SC 1.5%) were enrolled in regular transfusion programs. No differences were observed by age; however, there was a tendency toward a higher proportion of males compared to females in both age cohorts (adults 9.3% vs 6.9%; pediatric 8.5% vs 4.9%). Conclusions Interestingly, this analysis shows that SC patients experience high rates of chronic complications, in some cases exceeding those in SCA. Their Hydroxyurea usage also increases with age. These findings support the idea that SC is a moderate phenotype in pediatrics that worsens to severe over time and has historically been underestimated. As a European cross-border patient registry, RADeep enables robust data-driven research to optimize care pathways. It provides a framework for generating regulatory-grade real-world evidence and offers standardized data to support patient cohort identification for advanced clinical research in SCD.
Source: Blood
Authors: Anna Collado Gimbert, Sara Reidel, Raffaella Colombatti, Eduard Van Beers, Paola Bianchi, Stella Tamana, Angelo Loris Brunetta, Dore Peereboom, Giovanna Russo, Daniela Cuzzubbo, Elena Cela, José Manuel Marco Sánchez, Sarah Wambacq, Dedeken Laurence, Mariane de Montalembert, Karin Fijnvandraat, Bart Biemond, Frederic Galacteros, Pablo Bartolucci, Andreas Glenthoej, Antonis Kattamis, Ilona Binenbaum, María Pilar Nicolás, Iñigo de Miguel Beriain, Alexis Rodriguez Gallego, Angela Menarguez Lopez, Maximo Tartaglia, Nuria Torquet Luna, Roberta Trapanese, Betzabel Cajiao Garcia, Sandra Manceau, Kian Haseli, Efthymia Panteli, Elisabetta Mezzalira, Vincent De Pierrefeu, Petros Kountouris, Béatrice Gulbis, Maria Del Mar Mañú Pereira
Institutions: Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Universitat Politècnica de Catalunya, University of Padua, Azienda Ospedale - Università Padova, University Medical Center Utrecht, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Cyprus Institute of Neurology and Genetics, University of Catania, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco", Universidad Complutense de Madrid, Hospital General Universitario Gregorio Marañón, Université Libre de Bruxelles, Queen Fabiola Children's University Hospital, Hôpital Necker-Enfants Malades, Assistance Publique – Hôpitaux de Paris, Sanquin, University of Amsterdam, Rigshospitalet, National and Kapodistrian University of Athens, University of the Basque Country
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417011674
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