Behind the work
Sickle cell disease (SCD)
Sickle Cell Disease (SCD) is a hereditary blood disorder characterized by the production of abnormal hemoglobin, known as hemoglobin S. This mutation causes red blood cells to assume a rigid, sickle-like shape, leading to reduced oxygen delivery, chronic anemia, and painful vaso-occlusive episodes.
What Is Sickle Cell Disease?
Sickle Cell Disease (SCD) is a group of inherited blood disorders caused by mutations in the gene encoding the β‑globin chain of hemoglobin. Under low‑oxygen conditions, the abnormal hemoglobin variant (HbS) polymerizes, distorting red blood cells into a “sickle” or crescent shape. These sickled cells are less flexible, can become rigid, and obstruct small blood vessels, leading to reduced blood flow and tissue oxygenation.
SCD is inherited in an autosomal recessive pattern. A person must inherit two copies of the mutated gene (one from each parent) to have the disease; carriers with only one copy typically have the “sickle cell trait,” which often has mild or no symptoms. Early detection, often via newborn screening, allows for earlier interventions.
Pathophysiology: What Happens in the Body
In SCD, the sickling of red blood cells is not static—it’s a dynamic process. Repeated cycles of sickling and unsickling damage the red cell membrane, reduce deformability, shorten red cell lifespan, and trigger hemolysis (breakdown of red blood cells). Hemolysis releases cell contents like free heme, which can prompt oxidative stress, inflammation, and contribute to vascular injury.
Additionally, sickled cells obstruct capillaries (vaso-occlusion), which can cause acute painful crises, ischemia, and damage to organs (lungs, kidneys, brain, bone). Over time, repeated vaso-occlusive events lead to organ dysfunction. The disease also causes chronic anemia, which imposes stress on the cardiovascular system.
Clinical Presentation & Diagnosis
Symptoms often begin in early childhood. Common signs include severe pain episodes (“crises”), especially in bones, chest or abdomen; chronic anemia; swelling in hands/feet; increased risk of infection due to spleen dysfunction; acute chest syndrome (a serious pulmonary complication); stroke; and other organ complications.
Diagnosis involves:
Laboratory tests (e.g. hemoglobin electrophoresis or DNA analysis to identify HbS and other variants)
Blood counts, reticulocyte count, markers of hemolysis (bilirubin, LDH)
Imaging for organ damage, especially in lungs, brain, and kidneys
Treatment & Management
Management is multifaceted, aiming to reduce episodes of pain, prevent complications, manage anemia, and improve quality of life. Interventions include:
Hydroxyurea: Increases production of fetal hemoglobin which reduces sickling episodes.
Crizanlizumab, Voxelotor and other newer pharmaceuticals: These target specific disease mechanisms (adhesion, hemolysis) and have shown benefit in reducing crises or improving hemoglobin levels.
Blood transfusions: Both chronic and acute transfusions to manage severe anemia or prevent complications like stroke.
Supportive care: Pain management, hydration, infection prevention (vaccines, prophylactic antibiotics for children), and monitoring/management of organ damage.
Recent Advances & Emerging Therapies
Gene therapy and gene editing are among the most promising frontiers. Recent regulatory approvals have introduced treatments that aim to correct or modify the underlying genetic defect in stem cells, offering the potential for long‑term remission or possibly a functional cure.
Other areas under active research include better biomarkers for early detection and disease monitoring; therapies to modulate the immune response; treatments to reduce long-term organ damage; and interventions that reduce pain frequency or severity. Research is also underway into more accessible diagnostics (including tools usable in low‑resource settings) and algorithms (including machine learning) to predict crisis onset or optimize treatment pathways.
Challenges, Disparities & What’s Needed
Even with treatments improving, many challenges remain. Access to care is uneven—regions with fewer healthcare resources often see much worse outcomes. SCD disproportionately affects people of African ancestry, and social determinants of health (poverty, access to clinics, education) strongly influence outcomes.
There is also the need for more long‑term data on newer therapies (gene therapy, editing), including safety, durability, cost, and feasibility. Clinical trials often underrepresent certain populations. Research funding, provider training, and health system strengthening are critical. Public education remains necessary to reduce stigma and improve early diagnosis.