Sickle cell anemia

Sickle cell anemia (also known as sickle cell disease, hemoglobin SS disease, or drepanocytosis) is an inherited blood disorder caused by mutations in the HBB gene on chromosome 11, which encodes the beta-globin subunit of hemoglobin. The most common form results from homozygosity for the hemoglobin S (HbS) variant, in which a single amino acid substitution (glutamic acid to valine at position 6) causes hemoglobin molecules to polymerize under low-oxygen conditions, distorting red blood cells into a rigid, sickle-shaped form. These abnormal red blood cells have a shortened lifespan (approximately 10–20 days versus the normal 120 days), leading to chronic hemolytic anemia, and they can obstruct small blood vessels, causing vaso-occlusive crises. The disease affects multiple organ systems. Key clinical features include recurrent episodes of severe pain (vaso-occlusive crises), acute chest syndrome, stroke, splenic sequestration, chronic hemolytic anemia with fatigue and jaundice, increased susceptibility to infections (particularly encapsulated organisms due to functional asplenia), avascular necrosis of bones, pulmonary hypertension, and progressive organ damage affecting the kidneys, liver, eyes, and heart. Symptoms typically begin in infancy after fetal hemoglobin levels decline, usually around 5–6 months of age. Compound heterozygous forms such as HbSC disease and HbS/beta-thalassemia also produce sickle cell disease phenotypes of varying severity. The treatment landscape has expanded significantly. Hydroxyurea remains a cornerstone therapy, increasing fetal hemoglobin production and reducing the frequency of pain crises. L-glutamine, crizanlizumab (a P-selectin inhibitor), and voxelotor (a hemoglobin S polymerization inhibitor) are FDA-approved therapies. Regular blood transfusions are used for stroke prevention and management of severe complications. Allogeneic hematopoietic stem cell transplantation offers a curative option for selected patients. More recently, gene therapy approaches, including the CRISPR-Cas9-based therapy exagamglogene autotemcel (Casgevy) and the lentiviral gene therapy lovotibeglogene autotemcel (Lyfgenia), have received regulatory approval, representing transformative advances in curative treatment. Comprehensive care including newborn screening, penicillin prophylaxis, vaccination, and pain management remains essential.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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