Aplastic anemia is the medical term for bone marrow failure. The bone marrow, a spongy tissue inside the bones, is the factory for all blood cell lines -- red cells, white cells, and platelets. These cells are critical to supplying oxygen and nourishment to other tissues and organs, fighting infection, and in clotting the blood. Typically, as old blood cells die off naturally, they are replaced by new blood cells formed in the bone marrow. In aplastic anemia, the bone marrow does not produce new cells, leaving the body susceptible to organ failure, bleeding and infection.
Recently, researchers have discovered that most cases of severe aplastic anemia are autoimmune disorders in which the body’s own immune system attacks tissues and organs. They believe that autoreactive or abnormal immune cells known as lymphocytes suppress blood cell production and division. Though not technically a cancer, the treatment of aplastic anemia is often similar to therapies used for blood-forming cancers such as leukemias and lymphomas. As a result, the condition is most commonly treated in a cancer center.
A number of environmental factors, including drugs, high-dose radiation and chemotherapy, autoimmune and bone marrow disorders, benzene exposure, insecticides, and viruses have been identified as causes for the immune attack that leads to aplastic anemia. In many cases, the cause of aplastic anemia cannot be identified.
In aplastic anemia, the quantity of each of the three blood cell types is much lower than normal, which leads to symptoms that cause a physician to suspect the disease. These symptoms are unexplained infections (due to fewer white blood cells), unexpected bleeding (due to fewer platelets) and fatigue (due to fewer red blood cells).
Overall, the most common symptoms of aplastic anemia include:
- Significant fatigue
- Shortness of breath
- Recurring infections and/or flu-like symptoms
- Bruising or bleeding easily
- Difficulty in controlling bleeding, even from very minor wounds
- The appearance of small red dots on the skin that indicate bleeding under the skin
Severe aplastic anemia is a serious disorder requiring prompt medical attention. Physicians may want to perform a variety of tests. To diagnose aplastic anemia, physicians must examine the cells of the bone marrow and blood under a microscope. To do this they will likely perform blood and laboratory tests as well as a bone marrow aspiration and biopsy. In this test, a sample of bone marrow is removed from the hipbone with a special needle under local anesthetic. The physician will check the number of blood cells, including white cells known as neutrophils, clotting cells known as platelets, and young regenerating red cells known as reticulocytes. Because of a link between hepatitis and aplastic anemia, physicians may also request a laboratory test that evaluates the level of liver enzymes. HLA-typing, a laboratory blood test, is usually performed to ensure that patients receive immune compatible blood and marrow products during treatment.
Staging is a process used to determine the severity of the condition. Classifying or staging aplastic anemia is based on the criteria of the International Aplastic Anemia Study Group, which defines levels according to the numbers of blood cells present in the blood tests and bone marrow biopsy. Aplastic anemia is classified as moderate (MAA), severe (SAA), or very severe (VSAA).
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 marrow, the soft, fatty tissue inside the bones, replacing bone marrow that is either not working properly or has been destroyed by chemotherapy or radiation. Stem cells may be taken from the patient before getting chemotherapy or radiation. They also may come from a relative or other donor, or from umbilical cord blood.
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. More information
Blood Transfusion – Platelet transfusions are the first course of treatment for any aplastic anemia patient who is severely deficient in these blood cells. The transfusions reduce the high risk these patients have of suffering a fatal hemorrhage. Transfusions of red blood cells can help combat the fatigue and shortness of breath experienced by aplastic anemia patients. The process may quickly stabilize aplastic anemia patients with severe blood cell deficiencies, but it is very rare for a patient to achieve a long-term recovery using this form of treatment alone.
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. Patients who have ongoing transfusion need to be monitored for "iron overload"—a condition that can damage the heart and liver—with a blood test to measure the body's store of iron. If it is too high, medications to remove excess iron may be prescribed.
Medications – Drug therapy is also used in the treatment of aplastic anemia. Immunosuppressive drugs like antilymphocyte globulin (ALG), antithymocyte globulin (ATG) and cyclosporine are used to weaken the immune system and allow the bone marrow to make more blood cells, so the immune system is no longer attacking the bone marrow. The medications also may be given before a stem cell transplant. Side effects include fever, high blood pressure and kidney problems.
Other medications used to treat aplastic anemia include antibiotics and growth factors, copies of substances that occur naturally in the body. These drugs, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and cytokines, may help stimulate the bone marrow to produce new blood cells, especially disease-fighting white blood cells. Growth factors may work well in combination with each other or with immune-suppressing drugs to relieve the signs and symptoms of aplastic anemia.
At Johns Hopkins
High-Dose Cyclophosphamide Research at Johns Hopkins shows that high doses of the chemotherapy drug cyclophosphamide, without bone marrow transplantation, can lead to long-lasting, complete remissions in severe aplastic anemia. High-dose cyclophosphamide can rid the body of the cells that cause aplastic anemia without destroying key blood and bone marrow-forming stem cells because these stem cells contain high levels of an enzyme called aldehyde dehydrogenase, which makes them resistant to the toxic effects of cyclophosphamide.
Dr. Robert Brodsky, director of the division of Hematology, and his colleagues in neurology and rheumatology are applying this approach in other severe autoimmune disorders including, scleroderma, myasthenia gravis, multiple sclerosis and autoimmune hematologic disorders.
Bone Marrow Transplantation
Aplastic anemia was one of the first diseases for which bone marrow transplantation was found to be effective. In this therapy, the patient's own non-functioning bone marrow is destroyed with drugs and/or radiation and replaced with donor bone marrow from a compatible donor, usually a sibling or other family member. The donor marrow is given intravenously to the patient and travels to the bone regenerating blood cells The donor marrow must match the patient's immune system in order to avoid graft rejection and other serious complications. When successful, bone marrow transplant is often a cure for aplastic anemia with few incidences of relapse. However, it is a very intensive therapy, and serious immune complications and infections are not unusual. Other non-life-threatening effects of bone marrow transplantation include sterility and temporary hair loss. Patients under age forty are the best candidates. Cure rates decline significantly in those over 40.
Bone marrow transplantation may not be an option for many patients. Age, other health-related factors, or the inability to find a HLA compatible donor may make a transplant too risky. Drug therapy with antithymocyte globulin (ATG) or antilymphocyte globulin (ALG) which stimulate the production of blood cells by suppressing the immune system, may be recommended for these patients. While drug therapy is not a cure for aplastic anemia, it may partially restore blood cell production. However, as many as 50 percent of patients relapse or develop other blood forming malignancies or disorders.