MECHANISMS, MANIFESTATIONS, DIAGNOSIS AND EMERGING TREATMENTS OF SICKLE CELL DISEASE: A COMPREHENSIVE REVIEW

Abstract

A single point mutation in the β-globin gene results in sickle cell disease, a hereditary hemoglobinopathy that produces aberrant hemoglobin S (HbS). Sickled hemoglobin polymerizes when it is deoxygenated. Normal red blood cells become sickled as a result of this mutation. Sickle cell disease leads to several clinical complications like chronic pain crises, anemia, acute and chronic chest syndrome, stroke, vaso-occlusion, organ damage and other life-threatening health concerns. Globally, sickle cell disease affects more than 7 million people significantly in Sub-Saharan Africa, also in India and the Middle East. Disease severity is influenced by fetal hemoglobin (HbF) levels. While hydroxyurea treatments have traditionally helped the increasing fetal hemoglobin levels to cure sickle cell disease. Recent studies show that novel pharmacologic agents and other gene-based therapies like selective allogeneic hematopoietic stem cell transplantations, CRISPR-Cas9 genome editing also help to cure this disease. This review summarizes the latest evidence on molecular basis, pathophysiology, clinical manifestations and relative evolving therapeutic strategies of sickle cell disease, highlighting the recent progress and challenges in improving patient outcomes worldwide.