Click here to view next page of this article


Aplastic Anemia

Aplastic anemia is not a common disease. Prospective studies report an annual incidence of 2 new cases per 1 million population. However, the rate is much higher in the developing world, where aplastic anemia may rival acute myelogenous leukemia in frequency of diagnosis in hematology clinics aplastic anemia, anemea. In formal studies in Thailand and China, the incidence has been determined to be about 3-fold higher than in the West. Industrial hygiene efforts to protect workers led to the virtual disappearance of benzene as a causative factor in aplastic anemia in the United States, but unregulated chemical exposures probably contribute to high rates of bone marrow failure elsewhere. Because aplastic anemia is one of the most feared toxic effects of medical drug use, even a few cases can have a profound impact on new drug development and on the pharmaceutical industry, as most recently illustrated by the fate of the antiepileptic felbamate and the decrease in

The prognosis in aplastic anemia is directly related to the quantitative reduction in peripheral blood cell counts, particularly the neutrophil number. Prior to the introduction of practical blood transfusions, patients died of congestive heart failure caused by anemia or to hemorrhaging due


Classification of acquired aplastic anemia


Secondary causes


Drugs and chemicals

Regular effects 

Cytotoxic agents

Benzene hexachloride

Idiosyncratic reactions 


Nonsteroidal anti-inflammatory drugs 

Sulfonamides Antithyroid drugs

Antiepileptics and psychotropics 

Cardiovascular drugs

Gold, penicillamine, allopurinol


Epstein-Barr virus (infectious mononucleosis)

Hepatitis virus 




Non -G

Human immunodeficiency virus (acquired-immunodeficiency syndrome)

Immune diseases 

Eosinophilic fasciitis Hypoimmunoglobulinemia 

Thymoma and thymic carcinoma 

Graft-vs-host disease in immunodeficiency

Paroxysmal nocturnal hemoglobinuria 



Definitive Therapies

The underlying pathology of aplastic anemia can be addressed by replacing absent hematopoiesis through stem cell transplantation or by quelling lymphocyte attack through immunosuppressive therapies, Bone marrow or, more recently, peripheral blood stem cell transplantation from a histocompatible sibling usually cures the underlying bone marrow failure. Survival rates have been reported to be as high as 90% from a single experienced institution and at 77% for registry data, which reflect more general experience. Graft rejection, a 

Allogeneic transplantation is available only to a minority of patients, since about 70% will lack a suitably matched sibling donor. Phenotypically identical alternative family donors are acceptable but are found for only an occasional patient. Many more donors are available outside the 

Immunosuppression is used in patients who are not candidates for stem cell transplantation due to either age or the lack of a suitable matched family donor. Antithymocyte globulin (ATG), which is licensed for use in the United States, is a horse immunoglobulin preparation derived from the sera of animals immunized with normal pediatric thymus tissue. Hematologic responses, which are usually equivalent to sufficiently improved blood cell counts such that the patient no

Antithymocyte globulin and ALG have distinctive toxic effects. As foreign proteins, they can elicit anaphylaxis in the host. A skin test is routinely examined for evidence of sensitivity, and patients who have a positive reaction are desensitized. Antithymocyte globulin is not specific for lymphocytes and can reduce already low platelet and neutrophil levels and convert the 

Many, perhaps most, patients with aplastic anemia are not adequately treated by a single 4-day course of ATG followed by a 6- to 12-month course of cyclosporine. Slowly declining blood cell counts signal a need to retreat, and patients usually respond to either an increase in

Only a few patients face an actual choice between allogeneic transplantation and immunosuppressive therapy. Analyses of large databases have not shown major differences in outcomes between these 2 therapeutic approaches. Nevertheless, transplantation is probably preferable for certain defined subgroups, especially young patients and those with very severe neutropenia. Patients in whom immunosuppressive therapy failed have later undergone successful transplantation from matched siblings or from unrelated donors.

Antithymocyte globulin and ALG reduce lymphocyte numbers, but transiently and modestly compared with cytotoxic chemotherapy. Part of their beneficial activity may be to induce tolerance, perhaps by specific deletion of activated lymphocytes. Both these quantitative and

Late Evolution

Aplastic anemia is closely related to other bone marrow failure syndromes. Myelodysplasia, paroxysmal nocturnal hemoglobinuria (PNH), and aplastic anemia are easily confused in the clinical classification of a patient with pancytopenia and a hypocellular bone marrow, and they may ultimately be shown to share pathophysiologic features with aplastic anemia. As patient survival has improved, so too has the opportunity to observe the chronic course of bone marrow failure. Apparent evolution of aplastic anemia to another process has been reported in a substantial minority of patients undergoing immunosuppressive therapy. In a Large European