Breaking the cycle Targeting the interplay between red blood cells and inflammation in sickle cell disease

Despite being the most common inherited hematological disorder, treatment options for sickle cell disease (SCD) remain limited. While recent advances in hematopoietic stem cell transplantation and gene therapy offer promising avenues, most patients cannot access these interventions. This highlights the urgent need for widely available, affordable disease-modifying therapies, alongside optimization of established treatments such as red blood cell (RBC) transfusion. Part I of this thesis focuses on improving RBC transfusion strategies for patients with SCD. It explores various approaches to optimization, including a reassessment of transfusion indications and strategies to prolong the survival of donor RBCs post-transfusion. Part II delves into the pathophysiology of SCD, with a particular emphasis on chronic inflammation and oxidative stress, aiming to identify potential targets for novel therapeutic interventions. Collectively, the studies presented in this thesis provide new insights for enhancing RBC transfusion strategies and for guiding the development of innovative disease-modifying therapies for patients with SCD.