From Wikipedia, the free encyclopedia - View original article
|Classification and external resources|
|Classification and external resources|
Aplastic anemia is a disease in which the bone marrow, and the blood stem cells that reside there, are damaged. This causes a deficiency of all three blood cell types (pancytopenia): red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia). Aplastic refers to inability of the stem cells to generate the mature blood cells.
It occurs most commonly in the teens and twenties, and also among the elderly. It can be caused by exposure to chemicals, drugs, radiation, infection, immune disease, and heredity; in about half the cases, the cause is unknown.
Aplastic anemia is treated with immunosuppressive drugs, typically either anti-lymphocyte globulin or anti-thymocyte globulin, combined with corticosteroids and cyclosporine, with a response rate of about 70%; this indicates that aplastic anemia has an auto-immune component. Stem cell transplant is also used, especially for patients under 30 years of age.
Aplastic anemia is also sometimes associated with exposure to toxins such as benzene, or with the use of certain drugs, including chloramphenicol, carbamazepine, felbamate, phenytoin, quinine, and phenylbutazone. Many drugs are associated with aplasia mainly according to case reports, but at a very low probability. As an example, chloramphenicol treatment is followed by aplasia in less than one in 40,000 treatment courses, and carbamazepine aplasia is even more rare.
Exposure to ionizing radiation from radioactive materials or radiation-producing devices is also associated with the development of aplastic anemia. Marie Curie, famous for her pioneering work in the field of radioactivity, died of aplastic anemia after working unprotected with radioactive materials for a long period of time; the damaging effects of ionizing radiation were not then known.
Short-lived aplastic anemia can also be a result of parvovirus infection. In humans, the P antigen (also known as globoside) is the cellular receptor for parvovirus B19 virus that causes erythema infectiosum (fifth disease) in children. Parvovirus causes complete cessation of red blood cell production. In most cases, this goes unnoticed, as red blood cells live on average 120 days, and the drop in production does not significantly affect the total number of circulating red blood cells. In people with conditions where the cells die early (such as sickle cell disease), however, parvovirus infection can lead to severe anemia.
In some animals, aplastic anemia may have other causes. For example, in the ferret (Mustela putorius furo), it is caused by estrogen toxicity, because female ferrets are induced ovulators, so mating is required to bring the female out of heat. Intact females, if not mated, will remain in heat, and after some time the high levels of estrogen will cause the bone marrow to stop producing red blood cells.
The condition needs to be differentiated from pure red cell aplasia. In aplastic anemia, the patient has pancytopenia (i.e., anemia, neutropenia and thrombocytopenia) resulting in decrease of all formed elements. In contrast, pure red cell aplasia is characterized by reduction in red cells only. The diagnosis can only be confirmed on bone marrow examination. Before this procedure is undertaken, a patient will generally have had other blood tests to find diagnostic clues, including a complete blood count, renal function and electrolytes, liver enzymes, thyroid function tests, vitamin B12 and folic acid levels.
The following tests aid in determining differential diagnosis for aplastic anemia:
Treating immune-mediated aplastic anemia involves suppression of the immune system, an effect achieved by daily medicine intake, or, in more severe cases, a bone marrow transplant, a potential cure. The transplanted bone marrow replaces the failing bone marrow cells with new ones from a matching donor. The multipotent stem cells in the bone marrow reconstitute all three blood cell lines, giving the patient a new immune system, red blood cells, and platelets. However, besides the risk of graft failure, there is also a risk that the newly created white blood cells may attack the rest of the body ("graft-versus-host disease").
Medical therapy of aplastic anemia often includes a short course of antithymocyte globulin (ATG) or antilymphocyte globulin (ALG) and several months of treatment with a cyclosporin to modulate the immune system. Mild chemotherapy with agents such as cyclophosphamide and vincristine may also be effective. Antibody therapy, such as ATG, targets T-cells, which are believed to attack the bone marrow. Steroids are generally ineffective, though are often used to combat serum sickness caused by ATG use.
In the past, before the above treatments became available, patients with low leukocyte counts were often confined to a sterile room or bubble (to reduce risk of infections), as in the case of Ted DeVita.
Regular full blood counts are required to determine whether the patient is still in a state of remission.
From 10 to 33% of all patients develop the rare disease paroxysmal nocturnal hemoglobinuria (PNH, anemia with thrombopenia and/or thrombosis), which has been explained as an escape mechanism by the bone marrow against destruction by the immune system. Flow cytometry testing is performed regularly in people with previous aplastic anemia to monitor for the development of PNH.
Untreated, severe aplastic anemia has a high risk of death. Treatment, by drugs or stem cell transplant, has a 5-year survival of about 70%, with younger age associated with higher survival.
Survival rates for stem cell transplant vary depending on age and availability of a well-matched donor. Five year survival rates for patients who receive transplants has been shown to be 82% for patients underneath the age of 20, 72% for those 20–40 years of age and closer to 50% for patients over the age of 40. Success rates are better for patients who have donors that are matched siblings and worse for patients who receive their marrow from unrelated donors.
Older people (who are generally too frail to undergo bone marrow transplants) and people who are unable to find a good bone marrow match, who undergo immune suppression have five year survival rates of up to 75%.
Relapses are common. Relapse following ATG/cyclosporin use can sometimes be treated with a repeated course of therapy. In addition, 10-15% of severe aplastic anemia cases evolve into MDS and leukemia.
Milder disease can resolve on its own.