Sickle cell disease is much more common than many people realize. More than 100,000 people in the United States have sickle cell disease and almost 2 million Americans carry the sickle cell trait. It is the most common inherited blood disorder; approximately one out of every 500 African Americans and one out of every 36,000 Hispanic Americans, have sickle cell disease, according to data from the National Institutes of Health.
It wasn’t long ago that people with sickle cell disease were not expected to survive childhood. Historical data from the 1970s, indicates that the average lifespan of sickle cell patients was only 14 years. Today, thanks to universal newborn screening, and innovative research and treatment, more than half of sickle cell patients in the United States live beyond 50 years.
Sickle cell disease was first described more than 100 years ago, and further molecular and genetic information about the disease has followed with advances in basic science, especially in genetics, hematology, and epidemiology. However, sickle cell disease is still a condition with lifelong implications of a chronic disease, with many toxicities resulting in significant morbidity and mortality. Daily life challenges remain for people living with sickle cell disease, especially in light of the COVID-19 pandemic.
Major medical and psychosocial issues continue for patients and providers as this disease is managed initially by pediatric hematologists, but barriers become substantial as patients mature and head into adulthood without clear transitions in care for the patients as well as the providers. Treatments are available including potentially curative approaches, but access to care has become a major roadblock for patients particularly as they grow out of the pediatric age.
This review will take a brief look at the current diagnosis and treatment of sickle cell disease and how it has evolved over the years. Some of the exciting recent medical advancements that have the potential to drastically improve the quality and length of life for patients with this often-debilitating disease will also be described.
Diagnosis and Early Treatment
In 1972, the federal National Sickle Cell Anemia Control Act established voluntary sickle cell disease screening; counseling, public and professional education; and research and training in diagnosing, treating sickle cell disease. Since then, we’ve learned that early detection of sickle cell disease in infants, utilizing newborn screening, has had a dramatic impact on the ability to initiate appropriate treatment. This includes starting prophylactic antibiotics, and referral to sickle cell physicians, which has had a dramatic impact on early mortality by protecting children from dying from complications related to the disease, such as sepsis from preventable infections.
Sickle cell disease is now diagnosed in many ethnic groups, but is still most commonly found in the African American population with approximately 1 in 13 African Americans having the sickle cell trait, according to the Centers for Disease Control and Prevention. Today, newborns in the U.S. are screened for sickle cell disease through a routine blood test that looks for hemoglobin S protein, the mutated form of the normal hemoglobin proteins that results in sickle cell disease when the abnormal gene is inherited from both parents.
Sickle cell disease can also be identified before birth through amniocentesis, a technique used with in vitro fertilization procedures, called pre-implantation genetic diagnosis (PGD), which allows providers to test embryos for the defective gene before implantation, for parents who carry the sickle cell trait.
In the first six months of life, most babies with sickle cell disease don’t have sickle related symptoms because they still are expressing fetal hemoglobin, which protects red blood cells from sickling. Fetal gene expression usually disappears as children mature, so their risks of sickle cell symptoms and crisis, become more prevalent including pain, vaso-occlusive crisis, and risks of serious infection (due to the disease infarcting their spleen), which is why it is imperative that sickle cell patients receive ongoing medical care throughout their childhood – most often with a pediatric hematologist.
Regular medical care, including vaccines and preventative antibiotics such as penicillin to aid in preventing infections, are an extremely important component of care in the health of the patients, especially during childhood.
Managing Sickle Cell into Adulthood – Crises in Care
Although the severity of symptoms and complications from sickle cell disease are unique to each patient, they often worsen over time as patients enter adulthood due to the chronic damage to many organ systems over time. In addition to being at risk for infection and acute pain crises, patients with sickle cell disease face an increased risk of heart, lung, liver, GI, eye, joint, bone, and kidney problems. Additionally, chronic anemia and pain, stroke or silent brain injury, leg ulcers, and many other morbidities contribute to the decreased quality of life experienced by patients as they get older.
We know that many of these complications are preventable when patients are managing their disease under the regular care of both their primary and hematology physicians. However, as pediatric patients grow into adulthood, many of them struggle to find long-term adult specialty sickle cell care and they begin to experience more symptoms including kidney damage, heart or lung problems, as well as narcotic addiction stemming from cycles of hospital visits for pain management during acute pain crises. Sickle cell patients, like many patients with chronic health conditions, are at added risk for complications or even death from COVID-19, underscoring the importance of the COVID-19 vaccination in this population.
The reality in 2022, is that sickle cell patients don’t have to live a life revolving around time in and out of hospitals. Most sickle cell treatment can be managed with medicine and regular check-ups. All physicians and providers need to understand that sickle cell patients need support, and help with access to appropriate care, since disease specific medications and routine medical care can drastically improve their lives.
Promising Treatments, Longer Life
Sickle cell disease is a serious, lifelong condition, but remarkable treatments have evolved over the past four decades, in a steady fashion. Today, hematologists are best able to manage the disease with preventative treatments and interventions including novel medications to prevent both short- and long-term toxicity. The safety and efficacy of blood transfusions, when needed, are also providing a valuable bridge toward the exciting new developments which have a goal of a cure with genetic correction of the sickle cell mutation.
For example, in 2017 the Food and Drug Administration (FDA) approved hydroxyurea for use in sickle cell patients age 2 and older. Hydroxyurea, a treatment for leukemia and some head and neck cancers, can prevent painful sickle cell episodes and reduce the need for blood transfusions by making a patient’s red blood cells more flexible by increasing fetal globin expression, and decreasing inflammation. Another recent FDA-approved treatment, oral L-glutamine therapy, is proving to be effective in reducing sickle cell crises in patients age 5 and older. The capabilities that these therapies have in preventing complications, makes a significant difference in quality of life for patients. Two new medications were recently approved for management and prevention of sickle related complications using entirely new pharmacological approaches to the abnormal physiology of sickle cells. This gives physicians more choices to improve the life of patients by, hopefully, decreasing sickle cell related complications.
Perhaps most exciting is the potential cure that blood and bone marrow transplants offer to some pediatric sickle cell patients. While finding a genetically compatible sibling or donor is a challenge and a stem cell transplant has significant potential complications, it’s a treatment we offer to selected sickle patients at Texas Oncology whom we believe can benefit from this approach. The challenge of finding unrelated donors for patients with sickle cell disease, as well as many other conditions, can be difficult, which is why it is critically important to increase the pool of blood and bone marrow transplant donors, especially among minorities. and other high risk populations. Gene therapy approaches are also now being actively researched and studied in clinical trials which may offer more options for curative therapy to patients in the coming years.
We continue to research and study sickle cell disease to enable more breakthroughs in how we care for patients and even cure more patients with the disease. Many physicians across multiple primary and subspecialty disciplines have a critical role to play in the care of these patients. However, even with new treatments, blood transfusions remain an important therapy for patients with sickle cell disease. Pivotal studies have shown that blood transfusions have helped patients with sickle cell disease by reducing recurrent pain crises, treatment and prevention of stroke, and other complications beyond the scope of this brief review including priapism and acute and chronic lung syndromes.
January is National Blood Donor Month and I’d be remiss if I didn’t ask those in our medical community to roll up their sleeves and donate to a local blood donation facility. Together let’s celebrate the victories in sickle cell treatment and commit to doing all we can to help patients thrive as they navigate life with sickle cell disease.
For more information visit TexasOncology.com.
This article originally appeared in the January 2022 issue of Dallas Medical Journal.