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.

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2025
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