What is the cause and management of sickle cell anemia?

From the Guidelines

Sickle cell anemia is caused by a genetic mutation in the hemoglobin gene (HBB) that leads to the production of abnormal hemoglobin S, resulting from a C to A substitution at codon 6 of the beta globin gene with replacement of glutamic acid by valine, as described in the study by 1. This genetic mutation leads to the production of abnormal hemoglobin S, causing red blood cells to become rigid and sickle-shaped, resulting in blockage of blood vessels, pain crises, and organ damage. The mode of inheritance of sickle cell anemia is autosomal recessive, meaning that a person must inherit two copies of the mutated gene (one from each parent) to express the disease. Management of sickle cell anemia involves comprehensive care, including:

• Pain control with NSAIDs, opioids (morphine, hydromorphone) for severe pain, and preventive measures
• Hydroxyurea (starting at 15-20 mg/kg/day) as the primary disease-modifying medication, which increases fetal hemoglobin production, reducing sickling episodes
• Other treatments, such as L-glutamine (10-30 g daily), voxelotor (1500 mg daily), and crizanlizumab (5 mg/kg IV monthly), to prevent complications
• Regular vaccinations (pneumococcal, meningococcal, influenza), penicillin prophylaxis (125-250 mg twice daily in children), folic acid supplementation (1 mg daily), and hydration (2-3 liters daily)
• Blood transfusions for severe anemia, acute chest syndrome, or stroke prevention
• Bone marrow transplantation, which offers the only potential cure but carries significant risks Regular screening for complications affecting the eyes, kidneys, heart, and lungs is essential, as described in the study by 1. This multifaceted approach helps manage symptoms, prevent complications, and improve quality of life for patients with this inherited blood disorder. Key considerations in the management of sickle cell anemia include:
• The importance of early diagnosis and intervention to prevent long-term complications
• The need for individualized treatment plans, taking into account the patient's specific needs and medical history
• The role of patient education and support in promoting adherence to treatment and self-management strategies
• The importance of regular follow-up and monitoring to adjust treatment plans as needed and prevent complications.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Genetic Mutation Responsible for Sickle Cell Anemia

• The genetic mutation responsible for sickle cell anemia is a single point mutation in codon six of the β-globin gene (HBB) 2, 3, 4, 5.
• This mutation leads to the substitution of glutamic acid to valine at the sixth position of the β-globin chain, resulting in the formation of abnormal hemoglobin, HbS 3, 5.
• HbS is less soluble when deoxygenated than hemoglobin A (HbA), causing aggregates of HbS to form inside sickle erythrocytes and leading to chronic hemolysis and microinfarction of diverse tissues 3.

Mode of Inheritance

• Sickle cell anemia is an autosomal recessive disease, meaning that an individual must inherit two copies of the mutated β-globin gene (one from each parent) to express the disease 2, 3, 6.
• Individuals who inherit only one copy of the mutated gene are considered carriers and are generally asymptomatic, but can pass the mutation to their offspring 6.

Management of Sickle Cell Anemia

• Current management of sickle cell anemia includes various treatments aimed at reducing symptoms and preventing complications, such as pain crises, acute chest syndrome, and stroke 3, 6.
• Recent advances in gene therapy and gene editing strategies offer potential curative approaches for sickle cell disease, including the correction of the β-globin gene mutation in hematopoietic stem cells 2, 4.
• Other factors that can influence the severity of sickle cell disease, such as fetal hemoglobin expression and beta-globin cluster haplotypes, are also being explored as potential therapeutic targets 3, 4, 6.