Hemoglobinopathies, namely β-thalassemia and sickle cell disease (SCD), are hereditary diseases, characterized by molecular genetic aberrations in the beta chains of hemoglobin. These defects affect the normal production of hemoglobin with severe anemia due to less or no amount of beta globins in patients with β-thalassemia (quantitative disorder), while SCD is a serious disease in which a mutated form of hemoglobin distorts the red blood cells into a crescent shape at low oxygen levels (qualitative disorder). Despite the revolutionary progress in recent years with the approval of gene therapy and gene editing for specific patients, there is an unmet need for highlighting the mechanisms influencing hemoglobin production and for the development of novel drugs and targeted therapies. The identification of the transcription factors and other genetic modifiers of hemoglobin expression is of utmost importance for discovering novel therapeutic approaches for patients with hemoglobinopathies. The aim of this review is to describe these complex molecular mechanisms and pathways affecting hemoglobin expression and to highlight the relevant investigational approaches or pharmaceutical interventions focusing on restoring the hemoglobin normal function by linking the molecular background of the disease with the clinical perspective. All the associated drugs increasing the hemoglobin expression in patients with hemoglobinopathies, along with gene therapy and gene editing, are also discussed.

Sickle cell disease patients often need regular blood transfusions to improve both the quality of life and survival from the veno-occlusive complications of the disease. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with promising efficacy.This study aims to evaluate the association of liver stiffness and possible fibrosis with iron deposition and confirm the use of elastography as a validated test of responding to chelation with low cost and easy access. 15 patients with sickle cell disease and systemic or occasional transfusionswere evaluated with MRI,transient elastography and biochemistry, for liver iron(LIC) and liver stiffness(LSM) before onset and one year after taking Deferasirox.All patients completed the study.Our results showed improvement in hepatic iron and hepatic stiffness after chelation therapy; Furthermore ALT, AST, LDH and ferritin levels have improved after 12 months of therapy with deferasirox.During the study no serious adverse events were encountered indicating the safety of the drug.Transient liver elastography findings correlate with serum ferritin and LIC in patients with sickle cell disease and it is a useful tool for assessing the response of liver iron chelation therapy. Keywords: Sickle cell disease, iron chelation, transient elastography, transfusion, iron overload

Background and Objectives: Adrenal insufficiency (AI) can be a significant concern in patients with transfusion-dependent homozygous beta thalassemia (bThal) due to the chronic disease burden and frequent blood transfusions that these patients require. The prevalence of AI in this population remains unclear, with studies often lacking control groups for comparison. This meta-analysis aimed to estimate the proportion of patients with transfusion-dependent bThal who exhibit evidence of AI. Materials and Methods: A systematic review following PRISMA guidelines identified 19 studies for analysis. Results: Despite the variability in the diagnostic methods used to ascertain AI, the meta-analysis revealed that approximately one-third of patients had evidence of AI, with the prevalence rising to 50% in studies focused on adults with bThal. Conclusions: These findings suggest an increased risk of AI in patients with bThal compared to the general population. Clinicians should consider tailored management strategies, including glucocorticoid coverage during surgical procedures, to mitigate the risk of adrenal crises in this vulnerable patient group. Further research is needed to optimize adrenal surveillance and management in patients with bThal.

Extramedullary hematopoiesis (EMH) serves as a compensatory mechanism in chronic hemolytic anemias, such as thalassemia, and can result in spinal cord compression. This case report highlights a 36-year-old woman with transfusion-dependent β-thalassemia (TDT) who presented with lower extremity motor deficiency, pelvic paresthesia, and bladder dysfunction. The patient had a history of lower back pain, bilateral lower limb weakness, and demonstrated poor compliance with iron chelation therapy. MRI findings indicated spinal cord compression attributable to extramedullary hematopoiesis. Due to the infeasibility of surgical intervention, the patient underwent hypertransfusion and iron chelation therapy. While neurological symptoms improved, urinary retention persisted. The patient continues to receive iron chelation treatment and undergo transfusions. Managing extramedullary hematopoiesis in thalassemia necessitates an individualized treatment approach.