Sickle cell disease

Sickle cell disease (SCD) is a group of inherited disorders caused by disease-associated variants in the genes for hemoglobin. In common forms, a person inherits a hemoglobin S gene paired either with another hemoglobin S gene or with a different abnormal hemoglobin gene. The most familiar form, sickle cell anemia (HbSS), results when a person inherits a hemoglobin S gene from each parent; other forms include HbSC and HbS beta-thalassemia. Hemoglobin is the protein in red blood cells that carries oxygen. Sickle cell trait, usually HbAS, is different: a person has one hemoglobin S gene and one usual hemoglobin A gene and generally does not have SCD. The particular inherited combination helps determine disease severity, which varies among people.

When hemoglobin S molecules gather together inside red cells, the cells can become stiff, sticky and crescent-shaped. They are more likely to break apart prematurely, contributing to chronic anemia, and can block blood flow through small vessels. These blockages can cause episodes of acute pain and deprive tissues of oxygen; repeated injury can contribute to long-term complications. Health problems can include infections, acute chest syndrome, stroke, and damage affecting organs such as the kidneys, lungs, spleen and brain. Symptoms and their frequency are not the same for everyone, and the disease can affect health from childhood throughout life.

SCD can be identified with blood tests that detect abnormal hemoglobin. In the United States, it is often detected through routine newborn screening; screening and diagnostic programs differ across countries. Early identification allows care teams to monitor health and begin preventive measures. Care may include vaccinations and other steps to lower infection risk, regular assessment for complications, and prompt treatment of acute problems. Because SCD affects multiple organs and can change over time, care is often coordinated among clinicians with relevant expertise.

Treatment is tailored to the person and may combine preventive care, medicines, pain management and blood transfusions. Hydroxyurea can reduce red-cell sickling and lower the risk of some complications. Transfusions are used in particular situations, including to help prevent or treat serious problems. A blood or bone-marrow stem-cell transplant can provide a potential cure for selected patients but has important risks and is not suitable for everyone. In December 2023, the U.S. Food and Drug Administration approved two cell-based gene therapies for patients aged 12 years and older: Casgevy for those with recurrent vaso-occlusive crises and Lyfgenia for those with a history of vaso-occlusive events. Both involve modifying the patient's own blood stem cells and require high-dose chemotherapy before the cells are returned. These complex treatments are not appropriate or accessible for everyone, and their approval in one country does not establish availability elsewhere. Research continues on improving treatment and expanding access to effective care.

SCD occurs worldwide and is especially common among people with ancestry from parts of sub-Saharan Africa, the Mediterranean, the Middle East and India, although it is not confined to any one population. The World Health Organization, drawing on Global Burden of Disease estimates, reported that about 7.74 million people were living with SCD globally in 2021 and estimated 515,000 affected births that year. These modeled estimates underscore the need for newborn screening where feasible, reliable access to essential medicines and comprehensive long-term care. Unequal access to diagnosis and treatment contributes to preventable complications and deaths.