Sickle cell disease (SCD) is a genetic blood disorder impacting red blood cells, which carry oxygen throughout the body. In individuals with SCD, red blood cells take on an abnormal, rigid, and sticky sickle or crescent shape, unlike healthy, round, and flexible red blood cells. This altered shape leads to significant health challenges, including pain, organ damage, and other serious health problems.
The Genetic Basis
Sickle cell disease is an inherited condition. It occurs when a person inherits two abnormal copies of the beta-globin gene, one from each parent. This gene, located on human chromosome 11, provides instructions for making part of hemoglobin, the oxygen-transporting protein in red blood cells. The genetic change in SCD leads to the production of atypical hemoglobin S (HbS), which replaces normal adult hemoglobin (HbA).
Healthy red blood cells contain hemoglobin A, allowing them to remain soft, round, and flexible, easily navigating through small blood vessels. In contrast, red blood cells with mostly HbS become stiff and distorted into a sickle shape, especially under low-oxygen conditions. These rigid, abnormal cells cannot move smoothly through tiny blood vessels. Sickled cells also have a significantly shorter lifespan, dying in 10 to 20 days compared to 90 to 120 days for healthy red blood cells. This premature destruction contributes to a constant shortage of red blood cells.
Impact on the Body
The abnormal shape and rigidity of sickle cells have widespread effects. These cells often get stuck in small blood vessels, blocking blood flow and preventing oxygen from reaching tissues and organs. This obstruction leads to pain, often as sudden, severe episodes known as sickle cell crises or vaso-occlusive crises (VOCs). These painful episodes result from ischemia and tissue damage due to blocked blood flow, affecting any part of the body, including the chest, back, limbs, and joints.
A persistent shortage of healthy red blood cells due to their premature destruction leads to anemia. Anemia can cause symptoms such as fatigue, paleness, dizziness, and shortness of breath. The rapid breakdown of red blood cells can also lead to jaundice, characterized by yellowing of the skin and eyes. Children with SCD may experience delayed growth or puberty due to insufficient oxygen and nutrients.
Sickle cell disease can lead to severe complications affecting multiple organ systems. Acute chest syndrome (ACS) is a serious emergency where sickled cells block blood and oxygen supply to the lungs, leading to symptoms like chest pain, fever, and difficulty breathing. Stroke can occur if sickled cells block blood flow to the brain, causing weakness, numbness, or speech difficulties. Organ damage is common, as sustained lack of oxygen-rich blood can harm organs such as the kidneys, liver, and spleen. The spleen, which protects against infections, is particularly vulnerable to damage in SCD, increasing susceptibility to severe bacterial infections like pneumonia and meningitis.
Other complications include:
- Painful swelling of the hands and feet (dactylitis)
- Vision problems due to blocked blood vessels in the eyes
- Leg ulcers
- Increased risk of blood clots
Diagnosis and Treatment
Diagnosing sickle cell disease often begins with routine newborn screening in the United States, typically through a heel prick test. This initial screening checks for abnormal hemoglobins. If SCD is suggested, confirmatory blood tests like hemoglobin electrophoresis, high-performance liquid chromatography (HPLC), or isoelectric focusing are performed to confirm the diagnosis and identify the specific type of SCD. Prenatal testing can also diagnose SCD before birth using samples of amniotic fluid or placental tissue.
Management of SCD focuses on preventing complications and alleviating symptoms. Preventative measures include vaccinations and antibiotics to reduce infection risk, given the spleen’s impaired function in many individuals with SCD. Newborns with severe SCD often receive daily antibiotics until age five to prevent bacterial infections. Pain management strategies address pain crises, ranging from nonsteroidal anti-inflammatory drugs (NSAIDs) for milder episodes to intravenous opioids for severe pain.
Several medications manage SCD. Hydroxyurea is a commonly prescribed oral medication that can reduce the frequency of pain crises, acute chest syndrome, and the need for blood transfusions by increasing fetal hemoglobin (HbF), which helps prevent red blood cell sickling. Other medications, such as voxelotor and crizanlizumab, aim to prevent red blood cells from sickling or sticking to blood vessel walls, improving blood flow. Blood transfusions are also a common therapy, used to treat severe anemia, manage crises, and prevent complications like stroke by providing healthy red blood cells. For certain patients, a bone marrow or stem cell transplant offers a potential cure by replacing diseased bone marrow with healthy donor cells, though this intensive treatment carries significant risks and requires a compatible donor.