Use of the Hemanext One® Hypoxic Red Blood Cell Storage System for Transfusion in Thalassemia Patients

Transfusion-dependent β-thalassemia (TDT) is a severe inherited hemoglobinopathy requiring lifelong red blood cell (RBC) transfusions every 2 to 4 weeks. Patients typically receive 2-4 units per month, and their long-term survival and quality of life depend on the safety and functional integrity of the transfused RBCs. During standard storage, RBCs undergo progressive biochemical and morphological deterioration known as "storage lesions," which include oxidative damage, protein oxidation, enzymatic dysfunction, membrane remodeling, depletion of 2,3-diphosphoglycerate (2,3-DPG), and metabolic instability. These alterations reduce post-transfusion RBC survival and oxygen-delivery capacity and may contribute to hemolysis, increased transfusion requirements, iron accumulation, and other clinical complications. Oxygen exposure during storage is a major driver of oxidative injury, and reducing oxygen levels has been shown to mitigate the severity of storage lesions.

The Hemanext One® RBC Processing and Storage System is designed to reduce and maintain low oxygen and carbon dioxide levels during storage, thereby limiting oxidative deterioration of stored RBCs. Preclinical and early clinical evaluations have demonstrated improved preservation of RBC membrane integrity, metabolic profiles, and functional stability compared with conventional storage. The system has received FDA De Novo marketing authorization and CE marking. In Greece, RBC units processed with Hemanext One® are already used at the National Center for Blood Transfusion (EKEA) and are provided to selected thalassemia patients as part of standard clinical practice, independently of this study.

This study is prospective, observational, and entirely non-interventional. The investigators do not influence or assign transfusion type. All patients receive blood units according to routine clinical practice at EKEA, and participation in the study begins only after the patient signs informed consent. No study procedures or assessments occur before consent is obtained.

The study includes a 12-week baseline period, based on retrospective or prospectively collected routine clinical data during which the patient received conventionally stored RBCs. This is followed by an observational treatment period during which patients continue to receive hypoxically stored RBCs processed with the Hemanext One® system, exactly as provided by EKEA. The duration of this treatment observation phase is at least three months and may be extended until the study-wide data cut-off date, depending on RBC availability and patient preference. The study does not modify transfusion thresholds, clinical decision-making, or transfusion scheduling.

The primary objective of the study is to assess changes in transfusion burden, measured in cc/kg, after the transition from conventionally stored to hypoxically stored RBCs. Secondary objectives include the evaluation of changes in pre-transfusion hemoglobin, hemolysis and erythropoiesis markers, metabolic indicators, iron overload indices such as serum ferritin, patient-reported quality of life using validated instruments including the FACIT-F version 4 questionnaire, and the frequency and nature of transfusion-related adverse events. All information is obtained exclusively from routine clinical assessments and standard laboratory evaluations. No additional blood draws or study-specific procedures are required. A subset of patients may voluntarily contribute residual blood samples for more detailed laboratory evaluation, provided that these analyses are within the scope of routine laboratory capabilities.

All collected data will be coded and managed according to applicable data protection regulations. The investigators will not influence the assignment of blood unit type, which remains the responsibility of the transfusion service. This real-world evidence study aims to generate clinically meaningful insights into the safety, feasibility, and effectiveness of hypoxically stored RBCs in patients with TDT, supporting future evidence-based evaluation of their use in chronically transfused populations.

• Change from baseline in pre-transfusion hemoglobin. [Срок оценки: Up to 6 months]
• Change from baseline in fatigue-related quality of life using FACIT-F Version 4 [Срок оценки: Week 13, Week 24]
• Healthcare resource utilization [Срок оценки: Up to 6 months]
• Change from baseline in reticulocyte count [Срок оценки: Up to 6 months]
• Change from baseline in total bilirubin levels [Срок оценки: Up to 6 months]
• Change from baseline in lactate dehydrogenase (LDH) levels [Срок оценки: Up to 6 months]
• Change from baseline in serum ferritin levels [Срок оценки: Up to 6 months]
• Change from baseline in transferrin saturation [Срок оценки: Up to 6 months]
• Frequency of adverse events (AEs) [Срок оценки: Up to 6 months]
• Severity and seriousness of adverse events [Срок оценки: Up to 6 months]
• Relationship of adverse events to Hemanext transfusion [Срок оценки: Up to 6 months]