Sickle Cell Disease
Sickle cell disease is caused by an inherited genetic mutation that affects an individual’s hemoglobin, a protein within the red blood cells. When people inherit this form of hemoglobin, it impacts the way that red blood cells form in the body. Instead of developing as round disks, the red blood cells become crescent-shaped, like a sickle (the farming tool). These abnormal red blood cells are prone to breakage, and they don’t survive as long as healthy ones do. Because of this, people with sickle cell disease develop anemia and other complications. The condition also causes chronic and acute pain. It increases the risk of pneumonia and other infections, as well as stroke and organ damage.
About 100,000 people in the U.S. have sickle cell disease. Among people of African heritage – the group that is most affected by this condition within the U.S. – 1 in 500 people has the condition.
Therapies are available to reduce the frequency and severity of certain sickle cell disease symptoms.
What is sickle cell disease?
Sickle cell disease is the name for the group of inherited blood disorders that affect the red blood cells due to an abnormal form of hemoglobin that is passed from parent to child. When a person has sickle cell disease, their abnormal hemoglobin affects their red blood cells.
Healthy red blood cells are shaped like round disks. They’re durable and flexible, which allows them to move through the bloodstream easily. Hemoglobin, a protein within red blood cells, helps to bring oxygen throughout the body.
When a person has sickle cell disease, red blood cells form into sticky, fragile, rigid crescents instead of flexible disks. Crescent-shaped red blood cells are prone to breaking/dying before their expected lifespan. This causes anemia—a shortage of red blood cells.
Sticky, sickled red blood cells may also get caught in blood vessels, blocking blood flow. This prevents oxygen from reaching certain body parts. These blockages may cause intense pain (called a sickle cell crisis) and organ damage.
What causes sickle cell disease?
Sickle cell disease occurs when a person inherits mutations to the HBB gene. A genetic mutation causes the person to have abnormal hemoglobin, which changes the shape and texture of red blood cells.
To develop sickle cell disease, a person must inherit mutated HBB genes from both parents. If only one parent passes along a mutated HBB gene, the person will only be a sickle cell carrier –known as “sickle cell trait” – and will not experience symptoms of sickle cell disease. There is a 25% chance that a child of two parents with sickle cell trait will have sickle cell disease.
Some couples meet with genetic counselors before trying to become pregnant to see if both partners have the sickle cell trait. Knowing the risk of sickle cell disease may help couples with family planning.
What are the symptoms of sickle cell disease?
Babies with sickle cell disease may not experience symptoms until they are 4 to 6 months old. The condition causes a variety of symptoms among children and adults. Symptoms may change over time.
People who have sickle cell disease often experience anemia, which may cause:
- Shortness of breath
- A rapid heartbeat
- Jaundice, or yellowing of the skin and/or the whites of the eyes
Sickle cell disease may also cause:
- Abdominal pain
- Chest pain
- Swollen hands or feet
- Pain in the fingers, toes, arms, or legs
- Vision problems or blindness
- Cognitive difficulties
- Leg ulcers
- Bone infections
- Sleep apnea
- Urinary tract infections
- Bedwetting at night
- Chronic kidney disease
- Kidney damage
- Arthritic joint pain
- Deep vein thrombosis
- Swollen spleen
- Short stature
- Delayed growth
- Delayed puberty
- Heart failure
- Liver failure
How is sickle cell disease diagnosed?
Today most newborns in the U.S. are diagnosed in the hospital with a simple blood test. Since 2006, all hospitals in the U.S. have offered routine newborn screening tests to diagnose sickle cell disease.
Sometimes, when people know about a family history of sickle cell disease, a baby may be diagnosed in utero. Tests that can diagnose sickle cell disease in a fetus include:
- Chorionic villus sampling, during which a tiny portion of the placenta will be removed and its genetic makeup analyzed to look for signs of sickle cell disease
- Amniocentesis, during which doctors will remove a small amount of amniotic fluid that cushions the fetus within the mother’s uterus, to look for genetic mutations within the fluid.
It is also possible for older children and adults to be tested for sickle cell disease, particularly if they were not screened as newborns and are exhibiting symptoms. It’s also possible for people born outside of the U.S. to have sickle cell disease without a formal diagnosis. Tests are given to people with suspected sickle cell disease, such as:
- A complete blood count, which can identify the presence of anemia
- Hemoglobin electrophoresis, which can determine whether a person has abnormal hemoglobin
- High-performance liquid chromatography, which can identify the type of hemoglobin in a person’s blood
- DNA testing, which can determine whether there is a genetic mutation affecting the hemoglobin
How is sickle cell disease treated?
A variety of treatments (below) are available for people with sickle cell disease, including maintenance therapies and treatments to help patients who are in crisis.
Doctors may recommend that patients with sickle cell disease:
- Take antibiotics daily. This may prevent bacterial infections from arising in babies and children, who may be prone to infection.
- Stay well-hydrated. People with sickle cell disease are prone to dehydration, which may increase the risk of sickled red blood cells blocking the flow of oxygen to parts of the body.
- Take folic acid supplements. Folic acid helps the body create red blood cells. The formation of new cells may help alleviate symptoms of anemia.
- Get certain vaccinations. The Hib (haemophilus influenzae vaccine), PCV (pneumococcal conjugate vaccine), and PPV (pneumococcal polysaccharide vaccine) may help to reduce the risk of infection among babies and children.
- Take hydroxyurea, a prescription medication. It may prevent red blood cells from sickling and reduce the frequency of crises.
- Take other prescription medication.
Newer medications are available for sickle cell disease, including:
- L-glutamine, which may prevent red blood cells from forming blockages in blood vessels and may decrease the frequency of crisis-related pain.
- Crizanlizumab, which may reduce the incidence of red blood cells getting stuck in blood vessels, and may reduce the incidence of pain associated with crises.
- Voxelotor, which may increase hemoglobin levels in the blood.
- Use over-the-counter pain medication. Non-steroidal anti-inflammatory drugs (NSAIDs) may relieve pain. (Patients with kidney disease should take acetaminophen, not NSAIDs.)
- Receive blood transfusions. They increase the number of healthy red blood cells in the bloodstream, which enables more oxygen to be carried to tissue and organs throughout the body. A transfusion may help relieve chronic pain and reduce the risk of stroke.
When people with sickle cell disease develop complications, they may need the following:
- Eye surgery to manage vision problems
- Dialysis or kidney transplantation to manage kidney disease
- Gallbladder removal Advanced wound treatments for leg ulcers
What role does bone marrow (stem cell) transplant play in sickle cell disease treatment?
Bone marrow (stem cell) transplants have been used for the treatment and cure of a variety of cancers, immune system diseases, and blood diseases for many years. Doctors in the United States and other countries have developed studies to treat children who have severe sickle cell disease with bone marrow (stem cell) transplants. It is the only cure for sickle cell disease at this time.
As per American Society of Hematology, Stem Cell Transplant is considered a standard of care for patients with sickle cell disease who have a matched sibling donor and have or are experiencing the following:
- Multiple pain crises
- Recurrent acute chest syndrome
- Pulmonary hypertension
- History of stroke or high risk for developing stroke
- Development of antibodies to red blood cells
Results of studies show that transplants from matched related donors offer about a 90% chance of cure. With the rapidly expanding evidence of benefit reported by several groups, stem cell or bone marrow transplants have become an acceptable treatment option for sickle cell disease. Patients without a matching sibling donor who are experiencing severe complications related to their sickle cell disease have the option to undergo alternative donor transplants through clinical trials offered at Yale. Gene therapy is an emerging curative option offered through clinical trials for those with sickle cell disease who do not have any suitable donors. (Yale will be soon opening gene therapy clinical studies for sickle cell disease.)
How does a stem cell transplant cure sickle cell disease?
In a person with sickle cell disease, the bone marrow produces red blood cells that contain an abnormal form of hemoglobin, which leads to complications. In a bone marrow (stem cell) transplant, the patient’s bone marrow is replaced with blood-forming stem cells from a donor who does not have sickle cell disease.
It’s important to note that the transplant does not prevent a person from passing on the sickle cell gene; it only helps stop further sickle cell issues/complications from developing in the patient.
What is the outlook for people with sickle cell disease?
Decades ago, sickle cell disease was considered to be significantly life-shortening. Treatments have improved in recent years, allowing people with the condition to live longer and with a better quality of life.
People with sickle cell disease may live to age 50 or beyond, although they may not live as long as the average person. The cause of death is often organ failure or infections.
What makes Yale unique in its treatment of sickle cell disease?
“Yale Sickle Cell Program, which is unique to the New England area, offers comprehensive care with physicians, nurse practitioners, psychologists, dieticians, and social workers to provide state-of-the-art care, incorporating the latest medical innovations and technology tailored to each sickle cell patient,” says Niketa Shah, MD, director of the Yale Pediatric Bone Marrow Transplant Program. “It also offers, through clinical trials, an option of cure with bone marrow or stem cell transplant with alternative donor bone marrow transplant.”