Newer Modalities and Updates in the Management of Sickle Cell Disease: A Systematic Review

Zeel Vishnubhai Patel,1 Priyadarshi Prajjwal,2 Lakshmi Deepak Bethineedi,3 Divyakshi J Patel,4 Kaarvi Khullar,5 Hinal Patel,6 Kanishka Khatri,2 Mohammed Dheyaa Marsool Marsool,7 Srikanth Gadam,8 Soumya Aleti,9 Omniat Amir10 1Internal Medicine, Medical College Baroda, Baroda, Gujarat, India; 2Internal Medicine, Bharati Vidyapeeth University Medical College, Pune, India; 3Internal Medicine, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India; 4Internal Medicine, Smt. NHL Municipal Medical College, Ahmedabad, India; 5Internal Medicine, Maharashtra University of Health Sciences, Government Medical College, Gondia, India; 6Internal Medicine, GMERS Medical College and Hospital Sola, Ahmedabad, India; 7Internal Medicine, University of Baghdad, Al-Kindy College of Medicine, Baghdad, Iraq; 8Internal Medicine, NYC Health+ Hospitals, New York, NYC, USA; 9Internal Medicine, Berkshire Medical Center, Pittsfield, MA, USA; 10Internal Medicine, Al Manhal Academy of Science, SudanCorrespondence: Omniat Amir, Internal Medicine, Al Manhal Academy of Science, Khartoum, 1442, Sudan, Email [email protected]: Sickle cell disease (SCD), the most common autosomal recessive genetic disorder, affects the hemoglobin (Hb) chains in human red blood cells. It is caused by mutations in the β-globin genes, leading to the production of hemoglobin S, which results in the formation of sickle-shaped red blood cells (RBCs). These abnormal cells cause hemolysis, endothelial damage, and small vessel occlusion, leading to both acute and long-term complications. According to the World Health Organization’s 2008 estimates, SCD affects approximately 2.28 per 1000 individuals globally. Despite this high prevalence, therapeutic advancements have been slow. For many years, the only FDA-approved medications for managing SCD complications were hydroxyurea and deferiprone. However, recent years have seen the approval of several new therapies, including L-glutamine (2017), voxelotor and crizanlizumab (2019), as well as exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) (2023). These treatments have proven effective in managing both the acute and chronic effects of SCD, including hemolytic anemia, chronic pain, stroke, vaso-occlusive crises, and multiple organ damage syndromes. This review explores the mechanisms of action, practical considerations, and side effects of these emerging therapies, drawing from a comprehensive search of databases such as PubMed, Medline, and Cochrane.Keywords: sickle cell disease, L-Glutamine, Voxelotor, Crizanlizumab, Casgevy, Lyfgenia