Sickle cell anemia is an inherited, lifelong, serious disorder in which the body produces red blood cells with an abnormal, sickle shape, meaning they are shaped like the letter C. Normally, red blood cells are disc-shaped and move easily through the blood vessels. They contain an iron-rich protein called hemoglobin that gives blood its red color and carries oxygen from the lungs to the rest of the body. The cells also remove carbon dioxide (a waste product) from your body.
Sickle cells contain abnormal hemoglobin that causes the C shape. They are stiff and sticky, and tend to form clumps or get stuck in the blood vessels. These clumps block blood flow that lead to the limbs and organs, causing pain, serious infections or organ damage.
Normal red blood cells, produced in the spongy marrow inside large bones, last about 120 days in the bloodstream and then die. In sickle cell anemia, a lower-than-normal number of red blood cells occurs because sickle cells usually die after only about 10 to 20 days. The bone marrow can’t make new red blood cells fast enough to replace the dying ones.
Though not a cancer, the treatment of sickle cell anemia is often similar to therapies used for blood-forming cancers such as leukemias and lymphomas. As a result, the condition may be treated in a cancer center.
The risk of inheriting sickle cell anemia depends on genetics. Babies born with the disease inherit a copy of the sickle cell gene from each parent. The condition affects millions of people worldwide, and is most common in people whose families come from Africa, South or Central America (especially Panama), the Caribbean islands, Mediterranean countries (such as Turkey, Greece, and Italy), India, and Saudi Arabia.
In the United States, sickle cell anemia affects about 70,000 people, mainly African-Americans. The disease occurs in about 1 out of every 500 African-American births, and in 1 out of every 36,000 Hispanic-American births.
About 2 million Americans have the sickle cell trait, meaning they inherited only one copy of the sickle cell gene from one parent. These people usually have no symptoms and lead normal lives. However, they can pass the sickle cell gene to their children.
The symptoms of sickle cell anemia present after an infant is four months old. They can vary, with some people having mild symptoms and others having severe symptoms that cause them to be hospitalized for treatment. The most common signs and symptoms are linked to anemia and pain. Other signs and symptoms are linked to the disease's complications.
The most common symptom of anemia is fatigue (feeling tired or weak). Other symptoms include:
• Shortness of breath
• Coldness in the hands and feet
• Pale skin
• Chest pain
Another common symptom is sudden pain throughout the body, referred to as a sickle cell crisis. Sickle cell crises often affect the bones, lungs, abdomen, and joints. A sickle cell crisis occurs when sickled red blood cells form clumps in the bloodstream, blocking blood flow through the small blood vessels in the limbs and organs and causing pain and organ damage. The pain from sickle cell crises can range from mild to very severe, and last from hours to a few days. Chronic pain also can occur, lasting for months and severely limiting patients’ daily activities. Almost all people who have sickle cell anemia have painful crises at some point in their lives. Avoiding dehydration by drinking plenty of fluids can lower your risk for a painful crisis.
Other symptoms and complications include:
* Hand-foot syndrome – swollen hands and feet caused by sickle-shaped cells blocking blood flow out of the hands and feet. This may be the first sign in babies with the condition.
* Jaundice – a yellowing of the skin and eyes occurring due to liver damage.
* Frequent infections
* Delayed growth
* Vision problems
* Increased blood pressure in the lungs
* Ulcers on the legs
Sickle cell anemia is diagnosed through a blood test to check for hemoglobin S — the defective form of hemoglobin that underlies sickle cell anemia. In the United States, this blood test is part of routine newborn screening done at the hospital. In adults, a blood sample is drawn from a vein in the arm. In young children and babies, a blood sample is usually collected from a finger or heel. The sample is then sent to a laboratory, where it is screened for hemoglobin S. If the screening test is negative, there is no sickle cell gene present. If the screening test is positive, additional tests will be done to determine whether one or two sickle cell genes are present. People who have one gene — sickle cell trait — have a fairly small percentage of hemoglobin S. People with two genes — sickle cell disease — have a much larger percentage of the defective hemoglobin.
To confirm any diagnosis, a sample of blood is examined under a microscope to check for large numbers of sickle cells, and a blood test to check for anemia, a low red blood cell count, is done. Your doctor may recommend additional tests to check for complications related to the disease.
In some cases, sickle cell anemia can be diagnosed in an unborn baby by sampling some of the amniotic fluid surrounding the baby in the mother's womb to look for the sickle cell gene.
The only potential cure for sickle cell anemia currently is a bone marrow transplant, though finding a donor can be difficult, and there are serious risks associated with the procedure. Johns Hopkins physicians have developed a bone marrow transplant protocol that has been successful for sickle cell patients (see below). Other treatments are aimed at relieving symptoms or preventing crises.
At Johns Hopkins
Half-matched transplant Physician-scientists at Johns Hopkins have developed a procedure called a half-matched bone marrow transplant that has been successful in “curing” sickle cell anemia. Rather than wiping out a patient’s immune system before transplanting donor bone marrow, doctors administer just enough chemotherapy to suppress the immune system, which keeps patients from rejecting the donated marrow without harming their organs. And, the procedure expands the potential donor pool, making more patients eligible for the transplant.
Normally, doctors look for a donor who matches a patient's tissue type, specifically their human leukocyte antigen (HLA) tissue type. HLAs are proteins — or markers — found on most cells in the body. The immune system uses these markers to recognize cells that belong in the body versus those that do not. The closer the match between a patient's HLA markers and the donor’s, the better for the patient. In most sickle cell cases, doctors looked for a nearly full match prior to bone marrow transplantation. This was extremely difficult because in many cases, the person with the closest match, such as a sibling, may also have carried the sickle cell gene. The Hopkins procedure requires just a half-match, meaning that a patient’s parents or children could be suitable donors. With this option, doctors estimate that more than half of patients have potential matches.
Three days after the transplant, a patient is given a high dose of a drug called cyclophosphamide, which “re-boots” the immune system. The cyclophosphamide spares the donor's stem cells and allows them to establish new blood cells and a new immune system. The budding immune system is re-trained to see the patient's body as friend, preventing the patient from rejecting the transplanted bone marrow. Doctors estimate that a large percentage of patients treated this way may never have sickle cell disease again.
In March 2009, the Johns Hopkins bone marrow transplantation team successfully cured a 31-year-old woman of the disease using bone marrow donated by her mother. Video of Dr. Robert Brodsky, chair of hematology at Johns Hopkins, discussing this and other cases.
Sickle cell infusion center Johns Hopkins operates a Sickle Cell Center for Adults that provides comprehensive care including regularly scheduled outpatient visits, screening for hydroxyurea eligibility, genetic counseling, pain management, education, wound care and social services. The Center in June 2008 opened a sickle cell infusion center to rapidly treat patients battling crises. Read more on the infusion center in Johns Hopkins University magazine and Hopkins Medicine magazine.
Bone marrow transplant / Stem cell transplant A bone marrow transplant gives a patient healthy stem cells – immature cells that grow into different parts of the blood – taken from the bone marrow (the soft, spongy tissue inside bones) of a healthy donor who does not have sickle cell disease.
Most patients get high doses of chemotherapy, radiation, or both, before the bone marrow transplant to kill non-functioning marrow and make room for new stem cells to grow. Doctors deliver the stem cells through a tube injected into the bloodstream. They find their way into the bone marrow and begin reproducing to make healthy new blood cells. While receiving stem cells, patients may experience pain, chills, fever, hives, chest pain or other symptoms.
Blood Transfusion During a red blood cell transfusion, red blood cells are removed from a supply of donated blood and then given intravenously to a person with sickle cell anemia. Blood transfusions increase the number of normal red blood cells in circulation, helping to relieve anemia. They can decrease children’s risk of stroke.
During a transfusion, a technician will hang a bag containing the blood product you are receiving from a pole, then insert a narrow tube into a blood vessel in your arm. The healthy blood from a donor will drip from the bag through the tube and into your vein. The procedure usually takes about one to two hours, depending on what blood component(s) you are receiving.
Most people do not experience side effects from the procedure. Possible side effects include fever, allergic reaction or infection. Transfusions also increase the buildup of iron in the body, which, untreated, could lead to organ damage.
Medications Drugs used to manage sickle cell anemia include antibiotics to help fight infections, pain-relieving medications to lessen pain during crises, and hydroxyurea, which can reduce the frequency of crises or the need for blood transfusions.
Supplemental oxygen can help patients to breathe easier during crises.