The hemoglobinopathies are a group of inherited blood disorders caused by mutations affecting the globin genes and include sickle cell disease and the alpha (α-) and beta (β-) thalassemias. The β-hemoglobinopathies, genetic diseases caused by mutations affecting the beta globin gene, which include β-thalassemia and sickle cell disease, are among the most common inherited diseases worldwide.
Hemoglobin is the protein in red blood cells responsible for carrying oxygen to the body. In β-thalassemia, a subunit of adult hemoglobin protein is either not made at all or is made at severely reduced levels. This leads to fragile, dysfunctional red blood cells. The most severe form of β-thalassemia, transfusion-dependent β-thalassemia (TDT), is characterized by chronic anemia that must be managed with regular red blood cell transfusions.
People living with TDT rely on lifelong chronic red blood cell transfusions for survival (typically every 2-4 weeks), which deliver normal red blood cells with healthy hemoglobin to the body to improve anemia and suppress symptoms of the disease. However, most blood transfusions are administered for a half to a full day in the clinic (dependent on multiple factors), and coupled with other aspects of disease management often place a burden on caregivers and families.
Additionally, each unit of transfused blood contains 200 to 250 mg of elemental iron. While lifesaving, regular transfusions can cause iron to rapidly build up in the body, leading to iron overload, as the body cannot adequately eliminate excess iron. The accumulation of iron can be toxic to tissue and lead to damage of vital organs, such as the heart, liver, and endocrine glands, leading to organ dysfunction.3 Effective management of iron overload requires a carefully tailored transfusion protocol, continuous monitoring for iron toxicity levels, and the use of regular medications (also known as iron chelation) to remove excess iron.,
Sickle cell disease
Sickle cell disease (SCD) is a serious, progressively debilitating, and life-threatening genetic disease. SCD results from production of abnormal sickle hemoglobin (HbS), which leads to sickled red blood cells (RBCs) and hemolysis.
People with SCD produce abnormal hemoglobin, which distorts red blood cells into a sickle, or crescent shape. The sickled cells obstruct blood vessel circulation leading to chronic anemia, a condition where not enough healthy red blood cells are present to carry oxygen throughout the body. These obstructed cells can cause frequent vaso-occlusive episodes (VOEs), a common complication of SCD in adolescents and adults. VOEs are characterized by severe, unpredictable pain that can require hospitalizations; repeated VOEs and ongoing anemia can cause chronic organ damage, lead to infections, and cause strokes in children and adults with SCD, leading to poor quality of life and in many cases a shortened lifespan. The mean age of death for people with SCD in the United States is 44 years old.
Curative therapeutic options are limited, therefore, treatment for patients with SCD largely focuses on infection prevention, and management and prevention of VOEs. Standard treatments include opioids to manage the extreme pain patients experience and supportive care, such as penicillin, intravenous pain medication, and hydration. Disease-directed therapies include oral hydroxyurea, which treats and slows the progression of the disease, but incompletely stops lingering symptoms. Acute and chronic transfusion therapy can reduce the severity and progression of the disease, but with high associated medical and financial burden.
The only curative option is hematopoietic stem cell transplant with a matched donor, though less than 20 percent of patients have a matched sibling donor, and matched unrelated donors are hard to find for minority populations – people that are most affected by SCD.,
Given the lifelong need for comprehensive care, considerable healthcare resource utilization, and high rates of hospitalizations, including emergency room admissions due to severe and unpredictable pain crises, SCD represents a significant public health burden.
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