Sickle Cell Disease: Understanding its History, Symptoms, Treatment and Genetics
What is sickle cell disease?
Sickle cell disease is a common genetic condition that affects hemoglobin, a protein inside red blood cells (RBCs). The role of red blood cells is to carry oxygen throughout the body. Healthy RBCs are round and flexible and can easily move through the blood vessels in our body to deliver oxygen where it is needed.
For individuals with sickle cell disease, the abnormal hemoglobin molecules stick to themselves (called polymerization). This causes the RBCs to have an abnormal shape—a stiff and inflexible C-shape, like the old farm tool called a sickle.
These “sickled” red blood cells live for only 10 to 20 days compared to the 120-day lifespan of healthy red blood cells. This shortage of red blood cells results in a condition known as anemia. Stiff RBCs easily get stuck in blood vessels (called vaso-occlusion), which clogs the normal flow of blood and prevents the RBCs from effectively delivering oxygen to the body. This is what can cause many of the symptoms of sickle cell disease.
Symptoms of sickle cell disease
There are many short- and long-term complications of sickle cell disease. The hallmark is unpredictable and debilitating painful events, known as vaso-occlusive episodes or crises.
Many individuals with sickle cell disease experience pain every day of their lives. Sometimes pain is so severe that a visit to the emergency department or hospitalization may be required for acute management.
In addition to pain, other signs and symptoms of sickle cell disease include:
- severe anemia and fatigue
- serious infections
- jaundice (caused by breakdown of RBCs), resulting in yellowing of the eyes or skin and darkening of the urine
- stroke or other neurologic damage
- difficulties in school
- progressive damage to many organs including the heart, lungs, spleen, and kidneys
Treatments for sickle cell disease
Although sickle cell disease was first described over 100 years ago, no effective treatments were available until recently. Fortunately, we are now in an era where there is an increasing number of treatments becoming available for individuals with sickle cell.
Hydroxyurea is a once-a-day medication taken by mouth. It is the foundation of sickle cell disease treatment and is now used routinely beginning in the first year of life for children with the most severe type of sickle cell disease. It is used to prevent both short- and long-term complications of sickle cell disease.
Children who start hydroxyurea early in life can enjoy healthy lives similar to their peers who do not have sickle cell disease. Hopefully, they will grow up without knowing the suffering caused by frequent pain and complications of previous generations who did not have access to this medication.
For adults, hydroxyurea can reduce the frequency and severity of many symptoms of sickle cell disease. However, because hydroxyurea was not available when they were young, for many adults, some symptoms or chronic organ damage may not improve completely with hydroxyurea alone.
There are also three new FDA-approved medications for sickle cell disease that are now available, with many more in the pipeline. In addition, ongoing research to develop a cure for sickle cell disease through a treatment called “gene therapy” offers hope for the future.
Types of sickle cell disease
Sickle cell disease is a condition that people are born with; it is not acquired or contagious. In the United States, when babies are born, they are evaluated for dozens of conditions through a process called newborn screening. Sickle cell disease is the most-commonly identified condition through newborn screening, affecting about one in 2,000 newborns in the United States. Globally, sickle cell disease is quite common with a baby born once every two minutes with sickle cell disease, mostly in sub-Saharan Africa.
There are two major types of sickle cell disease – SS and SC. The letters describe the type of hemoglobin (S or C), with normal hemoglobin called hemoglobin A.
- SS is the most common and severe form, accounting for about two-thirds of all sickle cell disease in the U.S.
- SC is the second most common type of sickle cell disease that is often less severe type but can become more severe with age for many people.
Genetics of sickle cell disease and how it is passed from parent to child
As with all genetic features, everyone inherits one type of hemoglobin from each parent. People with sickle cell trait, sometimes called carriers, are labeled as AS, meaning they have one normal hemoglobin gene (A) and one abnormal sickle hemoglobin gene (S).
If two parents with sickle cell trait (AS) have a baby, there is a one in four chance for each pregnancy that the baby will have the SS form of sickle cell disease. Similarly, if one parent is a carrier for hemoglobin S (AS) and one is a carrier for hemoglobin C, there is a one in four chance that the baby will have the SC form of sickle cell disease.
If one parent is a carrier for S or C but the other parent does not carry an abnormal hemoglobin (AA), there is no chance that a baby will have sickle cell disease. Both parents need to be carriers (or have sickle cell disease themselves) to have a baby affected by sickle cell disease.
Most people with sickle cell trait do not have any symptoms and are often unaware they are a carrier of an abnormal type of hemoglobin. It is important to understand your sickle status and the potential risk of having a baby with sickle cell disease as you identify partners and begin to think about having babies.
The good news is that we now have highly effective treatments for sickle cell disease, and most babies born in this generation have the opportunity to live full and healthy lives.
The origin and distribution of sickle cell disease
The sickle cell mutation first happened generations ago to protect people against malaria, which is a serious and life-threatening infection common in certain parts of the world, including sub-Saharan Africa and India. Those individuals with sickle cell trait have a low risk of developing malaria and even if they do get malaria, are unlikely to die from it.
Due to this protective effect, in many African countries, as many as one in four people have sickle cell trait. This is also why most Americans with sickle cell disease are Black or Latinx with African ancestry.
Importantly, sickle cell disease is not a condition of skin color. People of any skin color can and do have sickle cell disease because of genetic mixing that has happened over the thousands of years since this mutation first occurred.
Transition of care from pediatric to adult medicine
Sickle cell disease is a lifetime transition that requires specialty care from the time of diagnosis as an infant through adulthood. Patients and their families receive most of their care in the same pediatric center for the first 20 or more years of their life, developing trust and comfort with their care team.
As children with sickle cell disease become adults, the “transition” of care to adult providers, usually between the ages of 18-22 years of age, is often a great challenge. In addition to the transition to adult life in general, patients are often learning to use the health care system by themselves for the first time.
Sometimes patients have problems getting to the doctor, using their insurance, or refilling their medications. Because of this, they can have a harder time managing their disease. This is an especially challenging time to develop a trusting relationship with a new care team.
In addition, adult sickle cell disease centers do not have the expanded resources that pediatric programs do. This disrupted care often results in increased sickle cell complications requiring emergency room or hospitalizations and an overall decreased quality of life. Here at Lifespan, we are working to reduce these disparities and aim to offer top-notch care regardless of age.
Healthcare disparities and sickle cell disease
Unfortunately, due to systemic racism, people living with sickle cell disease face many challenges related to stigma and bias. These challenges negatively impact their ability to receive high-quality and equitable care, most notably during acute, painful crises.
There have been a number of research studies demonstrating that many medical professionals harbor misconceptions about biological differences between black and white individuals (even though race is a social construct and not biological) and implicit biases based on their own life experiences which negatively impact the delivery of care, particularly related to pain management.
Due to the social construct of race in the U.S., sickle cell disease patients must not only face the consequences of a serious health condition, but also navigate a society in which the color of their skin is often an unfair disadvantage. Many sickle cell disease patients, as they suffer through and seek treatment for their debilitating pain, are often inappropriately labeled as drug seekers or are questioned as to the true degree of their pain. This causes inadequate pain management and further suffering. In many cases, patients even avoid the hospital because of this stigma and inadequate, biased care.
In this era of increasing efforts toward diversity, equity, and inclusion, we no longer should tolerate these inequities and must work to improve the care of individuals with sickle cell disease.
Lifespan Comprehensive Sickle Cell Center
The Lifespan Comprehensive Sickle Cell Center is working to merge our pediatric and adult programs into one entity that will provide comprehensive, equitable, and optimal care for patients throughout their life, from infancy through adulthood with a team of experts.
The goals of our growing sickle cell center are to:
- provide optimal clinical care
- participate in cutting edge research to further advance sickle cell disease care
- create a supportive sickle cell disease community for our patients and their families.
- fight against generations of inequity and structural racism with a zero-tolerance policy to reduce health-related stigma and bias in the care of sickle cell patients
Our sickle cell multidisciplinary clinic team of experts is focused on improving the lives of our patients using an anti-racist approach and fierce advocacy to speak up for and support our patients to eliminate the stigma and bias that has affected their care for far too long.
For more information, visit our website.
About the Author:
Patrick McGann, MD, PhD, Emily Franco, Margaret Lyons, and Helena Bates
Dr. Patrick McGann is a pediatric hematologist and an international sickle cell expert. He is the director of the new combined pediatric and adult sickle cell and hemoglobinopathy program at Rhode Island Hospital and its Hasbro Children’s Hospital.
Emily Franco is a medical student at The Warren Alpert Medical School of Brown University.
Margaret (Maggie) Lyons is a medical student at The Warren Alpert Medical School of Brown University.
Helena Bates is an undergraduate student at Brown University.
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