What is the inheritance pattern and management of sickle cell anemia?

From the Guidelines

Sickle cell anemia is inherited in an autosomal recessive pattern, meaning a person must inherit two abnormal hemoglobin S genes (one from each parent) to develop the disease. This pattern of inheritance is crucial in understanding the risk of developing sickle cell anemia and the potential complications associated with it 1. The management of sickle cell anemia focuses on preventing complications and treating symptoms through comprehensive care, including:

• Pneumococcal and influenza vaccines to prevent infections
• Daily folic acid (1 mg) supplementation to support red blood cell production
• Maintaining hydration to reduce the risk of vaso-occlusive crises
• Hydroxyurea (starting at 15-20 mg/kg/day) as the primary disease-modifying medication to increase fetal hemoglobin production and reduce painful crises 1
• Blood transfusions for severe anemia, stroke prevention in high-risk children, and acute chest syndrome
• Newer treatments such as L-glutamine (Endari), voxelotor (Oxbryta), and crizanlizumab (Adakveo) to reduce the frequency of painful crises and hospitalizations
• Bone marrow transplantation as a potential cure, but it carries significant risks and is typically reserved for severe cases.

It is essential to note that sickle cell trait, which occurs when an individual inherits one abnormal hemoglobin S gene, provides protection against malaria while causing minimal symptoms, whereas sickle cell disease, which occurs when an individual inherits two abnormal genes, causes red blood cells to become rigid and sickle-shaped under stress, leading to vaso-occlusion and hemolysis 1. The understanding of the inheritance pattern and the management of sickle cell anemia is critical in reducing morbidity, mortality, and improving the quality of life for individuals with this condition.

From the Research

Inheritance Pattern of Sickle Cell Anemia

• Sickle cell disease is caused by a variant of the beta-globin gene called sickle hemoglobin (Hb S) 2
• The disease is inherited autosomal recessively, meaning that either two copies of Hb S or one copy of Hb S plus another beta-globin variant are required for disease expression 2
• Hb S carriers are protected from malaria infection, which has led to a high frequency of Hb S in individuals of African and Mediterranean ancestry 2

Management of Sickle Cell Anemia

• Treatment options for sickle cell disease focus on managing symptoms and preventing complications 3
• Pain management with analgesics, hydration, and blood transfusions to improve oxygen delivery are common treatment approaches 3
• Hydroxyurea, a medication that increases the production of fetal hemoglobin, is commonly used to reduce the frequency and severity of pain crises 3, 4, 5, 6
• Bone marrow or stem cell transplants can cure select individuals with severe sickle cell disease 3
• Newborn screening, better medical care, parent education, and penicillin prophylaxis have successfully reduced morbidity and mortality due to Hb S 2

Role of Hydroxyurea in Sickle Cell Anemia Management

• Hydroxyurea has been shown to improve pain alteration and life-threatening illness in individuals with sickle cell disease 4
• Hydroxyurea may improve measures of fetal hemoglobin and decrease neutrophil counts 4
• The use of hydroxyurea has been associated with a reduced frequency of acute chest syndrome and blood transfusions 4
• However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly with regard to preventing chronic complications of sickle cell disease 4