Evaluation of Ineffective Erythropoiesis in Patients with Sickle Cell Anemia

• Grant number: 24/17048-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2024
• End date: July 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Fernando Ferreira Costa
• Grantee: Nicole Novais Santos
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 19/18886-1 - Pathophysiological mechanisms and treatment of red blood cell abnormalities, AP.TEM

Abstract

Erythropoiesis is the physiological process responsible for the production of erythrocytes that occurs mainly in the bone marrow. The formation and maturation of erythrocytes involve a series of complex molecular events, including the participation of multiple transcription factors, cytokines, and elements of the bone marrow microenvironment. Disorders in erythropoiesis can lead to inadequate production of erythrocytes, resulting in ineffective erythropoiesis (IE), which is characterized by a high rate of cell destruction, with insufficient production of mature erythrocytes. Sickle cell anemia (SCA) is an inherited genetic disease that fits into this context and that is characterized by a mutation in the hemoglobin gene, resulting in the production of hemoglobin S (HbS) instead of normal hemoglobin (HbA). The presence of hemoglobin S causes a distortion in the shape of erythrocytes, transforming them into a sickle shape when this hemoglobin polymerizes in situations of deoxygenation, which results in a series of clinical complications. Thus, IE is the result of the premature destruction of sickle-shaped erythrocytes and other mechanisms, leading to inadequate bone marrow compensation and persistent anemia. Quantifying IE can help assess the severity of diseases, monitor the effectiveness of treatments and improve the individualization of therapies, benefiting the quality of life of patients. Thus, this study aims to evaluate IE in patients with SCA, correlating clinical and laboratory data with the levels of the soluble transferrin receptor (sTfR) and the absolute reticulocyte count (ARC). The methodology includes analysis of medical records, determination of ARC and ELISA assays for plasma quantification of sTfR. The severity of IE in these patients, resulting from the ratio between sTfR and ARC levels, correlated with the clinical severity of AF, may serve as a marker to monitor the progression and efficacy of treatments.