Sickle Cell Disease and Anemia
Blood is living tissue comprised of plasma (the liquid part of blood) plus red blood cells (RBCs), white blood cells, and platelets. Hemoglobin, a protein component of RBCs, carries oxygen from the lungs to the rest of the body. The production and maturation of RBCs takes place in the bone marrow in a process called erythropoiesis; blood disorders can disrupt this process. Sickle cell disease (SCD), one of the most common genetic disorders affecting erythropoiesis, is caused by a specific mutation in a gene that codes for the β-globin component of the hemoglobin protein. The mutated version of hemoglobin results in distorted RBCs (a sickle-like shape rather than a normal round shape). The result is ineffective erythropoiesis and anemia—a condition in which the blood has a lower than normal level of RBCs or hemoglobin, and, thus lacks an optimal amount of oxygen-rich blood. These sickled cells clump together and stick in small blood vessels, resulting in severe pain, blood cell destruction, stroke, pulmonary hypertension, and organ failure. Anemia may be caused by other reasons. For example, anemia is a common and significant complication of chronic kidney disease. NIDDK-funded research has made important strides in developing new treatments for diseases like SCD and understanding anemia. Research into how cells detect oxygen and react to low oxygen levels was selected as the 2019 Nobel Prize in Physiology or Medicine.
- As recently as 1970, the average patient with SCD died in childhood, often of overwhelming infection.
- Approximately 10 percent of children with SCD suffered fatal or debilitating strokes due to lack of oxygen to the brain.
- Although the technology for screening newborns for SCD was available, it was not generally used since there were no proven therapies that could be used given an early diagnosis.
- Many persons with SCD were burdened with recurrent acute pain episodes and often with debilitating chronic pain, limiting their ability to attend school, maintain employment, and carry on with everyday activities.
Today and Tomorrow
Developing Strategies to Treat and Cure Sickle Cell Disease
- With decades-long investments in research, many people with SCD can live full lives and enjoy most of the activities that other people do with proper care and treatment.
- Based, in part, on NIDDK-supported research, hydroxyurea became the first agent approved by the U.S. Food and Drug Administration for prevention of painful sickle cell episodes in patients 2 years of age and older. Hydroxyurea increases life expectancy, reduces emergency department visits and hospitalizations, and is cost effective for gravely ill adult patients. Hydroxyurea works by increasing the concentration of fetal hemoglobin (the predominant form of hemoglobin at birth that typically drops to very low levels by 6 months of age) in the red blood cells of patients with SCD, thus diluting the concentration of sickled red cells. The drug is the only one approved by the FDA for treating SCD, and in many patients it reduces common complications such as severe pain, organ damage, and ameliorates anemia.
- The NIDDK and National Heart, Lung, Blood Institute have been supporting blood stem cell transplantation clinical studies in children and adults as an approach to reverse sickle cell disease. In these studies, the patient’s bone marrow is first primed to create space in their bone marrow. Patients then undergo a blood stem cell transplant, receiving cells donated by a healthy matched donor. These on-going studies have shown, in the majority of patients, that the stem cell transplants reversed the disease including the anemia, resulting in normal hemoglobin protein in the patients’ blood, fewer hospitalizations, and lower use of narcotics to treat pain from the disease.
- NIDDK continues to support research activities toward understanding some of the end organ damage that results from sickled red cells, in particular the effects on kidney function.
- NIDDK research is looking for new ways to reactivate fetal hemoglobin in patients with SCD.
- NIDDK continues to support research on the general process of erythropoiesis as well as research investigating novel disease targets for regulation of red blood cell development, and tools for translating these discoveries into therapeutic modalities. This research could help patients with SCD.
- NIDDK continues research investments in a prevalent type of anemia called “anemia of chronic disease” or “anemia of inflammation.” This typically mild to moderate anemia (to be referred to here as AICD) occurs as a complication of many clinical conditions, including acute and chronic infections, autoimmune diseases, kidney diseases, cancer, and post-operative recovery following major surgery. AICD is particularly common in hospitalized patients and in the elderly and may have a negative impact on the recovery, function, and survival of affected individuals.
- Due to careful and methodological clinical research studies, blood cell transplantation will be curative for most adults and children with SCD. Initially, this strategy was limited by the lack of suitable matched donors but continued research is working to overcome this hurdle by identifying strategies that reduce the matched donor requirement.
- Continued research should develop a better understanding of the altered physiological processes associated with disease and clinical impact of AICD and lead to improvements in the detection, prevention, and treatment of this common form of anemia.