What is sickle cell anemia?
The term sickle cell disease (SCD) describes a group of inherited red blood cell disorders. People with SCD have abnormal hemoglobin, the protein in red blood cells that carries oxygen, called hemoglobin S or sickle hemoglobin. The problem in hemoglobin S is caused by a small defect in the gene that directs the production of the beta globin part of hemoglobin. People who have SCD inherit two abnormal hemoglobin genes, one from each parent. When a person has two hemoglobin S genes, Hemoglobin SS, the disease is called sickle cell anemia. This is the most common and often most severe kind of SCD. Hemoglobin SC disease and hemoglobin Sβ thalassemia are two other common forms of SCD. Sickle cell disease is a life-long illness and the severity of the disease varies widely from person to person. A person has sickle cell trait and is generally healthy when the hemoglobin S gene is inherited from only one parent and a normal hemoglobin gene is inherited from the other..
Normal red blood cells (RBCs) that contain normal hemoglobin are shaped like a disc, are flexible and move readily through large and small blood vessels to deliver oxygen whereas the RBCs in patients with SCD are stiff rods and change into a crescent, or sickle shape. Sickle-shaped cells are not flexible and can stick to vessel walls, causing a blockage that slows or stops the flow of blood. When this happens, oxygen delivery to the tissues is hindered. Decreased tissue oxygen can cause attacks of sudden, severe pain, called a pain crisis. The red cell sickling and poor oxygen delivery can damage all of the body’s organs, including spleen, brain, eyes, lungs, liver, heart, kidneys and bones.
People with SCD who are born in the U.S. are detected at birth. Some children with SCD will start to have disease problems before one year of age, while some affected children develop disease problems later in childhood. People with SCD usually have mild to moderate anemia. Anemia is caused by the rapid destruction of sickle red blood cells compared to normal RBCs. However, patients can also manifest severe anemia that can be life threatening caused by either splenic sequestration, where the red blood cells get trapped in the spleen, or by an aplastic crisis where the bone marrow shuts down and stops making RBCs.
The most common complication of SCD is recurrent painful crises. Pain episodes can occur without warning and can strike almost anywhere in the body. A crisis may be initiated by a febrile illness, dehydration or stress. Frequent sites of pain include: the lower back, extremities, abdomen and chest. Sickling in blood vessels of the lungs can deprive a person’s lungs of oxygen. When this happens, areas of lung tissue are damaged and cannot exchange oxygen properly. This condition is known as acute chest syndrome; symptoms include: chest pain, fever, shortness of breath and cough. A stroke is another serious manifestation of SCD and occurs when blood flow is blocked to a part of the brain by sickled cells. When this happens, brain cells can be damaged or die. The symptoms depend upon what part of the brain is affected, but include: weakness of an extremity, loss of balance, trouble speaking, and severe headaches.
Patients with SCD have increased susceptibility to bacterial infections, and may be life-threatening. Pneumonia, meningitis, and osteomyelitis, bone infections, are common and may be related to a dysfunctional spleen that is unable to act as bacterial filter to remove the organisms from the blood stream.
Every state in the United States requires that every baby is tested for SCD as part of a newborn screening program. If a baby is found to have SCD, the diagnosis is confirmed by a simple blood test to determine whether they make sickle hemoglobin, hemoglobin S or another type of abnormal hemoglobin, such as C, or β thalassemia. The test called a hemoglobin electrophoresis can ascertain whether a person has a normal hemoglobin component of hemoglobin A and F, or carries a gene for SCD and thus has sickle cell trait and can pass it on to a child. if they inherited two abnormal genes, one from each parent and have only hemoglobin S, a diagnosis pf SCD is confirmed.
The management of patients with SCD is complex and requires the specialized care of a pediatric hematologist. In SCD, the spleen doesn’t work properly and this problem makes people with SCD more likely to get severe infections; therefore children are prescribed daily penicillin to reduce the chance of having a severe infection caused by the pneumococcus bacteria. They should receive all recommended childhood vaccines including immunizations against Pneumococcus, Meningococcus and influenza. People with SCD need to have frequent blood tests to establish a “baseline” for problems like anemia. Children between the ages of 2 and 16 should have a Transcranial Doppler (TCD) Ultrasound Screening on a yearly basis to determine whether a child is at higher risk for stroke. When the test is abnormal, regular blood transfusions can decrease the chances of having a stroke.
Managing the complications of SCD must be individualized. Painful crises should be managed with hydration and analgesics, infections with appropriate antibiotics, and anemia with RBC transfusions. Patients with stroke usually need a chronic transfusion regimen. Most children with SCD should take hydroxyurea, a daily medicine that increases the amount of hemoglobin F that has been shown to reduce or prevent several SCD complications. Some patients benefit from a RBC transfusion regimen to treat and prevent certain SCD complications. The red blood cells in a transfusion have normal hemoglobin and may decrease vaso-occlusion (blockage in the blood vessel) and improve oxygen delivery to the tissues and organs.
At the present time, hematopoietic stem cell transplantation (HSCT) is the only cure for SCD. In HSCT, donor stem cells are taken from the bone marrow or blood of a person who does not have SCD, and is otherwise genetically matched to the patient or recipient. After the stem cells are taken from the donor the patient with SCD is treated with drugs that destroy or reduce his or her own bone marrow stem cells. The donor stem cells are then injected into the recipient and make a home in the recipient’s bone marrow, gradually replacing the recipient’s cells. The new stem cells will make red cells that contain normal hemoglobin and thus do not sickle.