Since 2008, June 19th has been recognized as World Sickle Cell Day by the United Nations to raise awareness about sickle cell disease and support patients (known as “Sickle Cell Warriors”).
Sickle cell disease is a disorder of hemoglobin (Hb), inherited in an autosomal recessive fashion when one gene coding for sickle Hb (HbS) combines with any Hb gene other than HbA (normal Hb). An estimated 300,000 infants are born each year with sickle cell disease, with Nigeria, India and Democratic Republic of Congo accounting for more than half of the world’s sickle cell population. Other regions with high prevalence of sickle cell include other countries in sub-Saharan Africa, the Middle East, and Mediterranean regions; most countries in the world have individuals living with sickle cell disease. Given the lack of national registries in most countries, the actual number of individuals living with sickle cell worldwide is unknown. At present, about 100,000 patients live in the United States.
Sickle cell disease causes acute life-threatening complications beginning in early childhood, the most common being severe pain crises that often require opioids to obtain relief, as well as stroke and acute chest syndrome, which is the leading cause of death. In addition, sickle cell disease leads to progressive organ damage, affecting nearly every organ in the body. Individuals with sickle cell disease contend with significant morbidity and a shortened lifespan, with life expectancy of 54 years in the U.S. compared to 76 years for individuals without sickle cell disease.
In high-income countries, diagnosis of sickle cell disease is often made through newborn screening programs. However, the methods used to conduct newborn screening can be expensive to operate and require advanced training, and results are not quickly available. Solubility testing can qualitatively identify sickle hemoglobin but cannot reliably differentiate sickle cell disease from sickle cell trait (heterozygous carrier), and is inaccurate in many situations, such as severe anemia and leukocytosis. More recently, inexpensive point-of-care tests have been developed that rapidly identify HbS as well as HbC (common hemoglobin variant), but widespread adoption is stymied by insufficient funding and staff. In areas without newborn screening, infants and young children with sickle cell disease may present with severe complications associated with high mortality, including sepsis, splenic sequestration, and acute chest syndrome.
Individuals with sickle cell disease refer to themselves as Warriors, and rightly so. They face significant disease bias and stigma, and in the U.S., structural racism. Funding for sickle cell research is 10 times less than cystic fibrosis, a condition that affects mostly those of Northern European descent, and this gap has widened over the past 15 years which has significantly limited the availability of treatment options.
Despite the discovery of the genetic underpinnings of sickle cell in the late 1940s, the first FDA-approved medication, hydroxyurea, was only approved in 1998 for adults and 2017 for children. Over the past five years, L-glutamine, crizanlizumab, and voxelotor have been approved as adjunctive and second-line therapies, but their long-term impact on sickle cell disease is currently unknown. Hematopoietic stem cell transplant is the only curative option, with best results seen for those with a matched sibling donor. However, most Warriors worldwide do not have access to this therapy due to expense and lack of available matched donors.
In the U.S., there aren’t enough clinicians trained to manage adult Warriors with sickle cell disease in the outpatient setting, further limiting access to disease-modifying therapies. Those working in acute care settings, especially in emergency departments, have limited education on the myriad of complications associated with this condition, including managing pain crises, leading to poor quality care. Since 2015, national organizations, including American Society of Hematology and American College of Emergency Physicians, have supported several initiatives for sickle cell disease. These include the creation of a point-of-care tool for the management of pain in the ED and workforce development workshops to increase the number of clinicians with expertise to manage sickle cell disease to increase access to appropriate care.
Although much work needs to be done to make high-quality care available to all Warriors living with sickle cell disease, enhanced focus on therapeutic research, workforce development, and public health initiatives to increase newborn screening in many countries (including Nigeria and India), gives cause for hope. With continued efforts nationally, regionally, and globally, sickle cell disease may no longer be the poster child for health equity.
