Neal S. Young, MD
Acknowledgments: The author thanks Drs. Jaroslaw Maciejewski, John Barrett, Elaine Sloand, and Cynthia Dunbar for their careful reading of the manuscript.
Grant Support: Dr. Young is supported entirely by intramural funds from the National Heart, Lung, and Blood Institute.
Requests for Single Reprints: Neal S. Young, MD, Building 10, Room 7C103, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-1652.
In aplastic anemia, hematopoiesis fails: Blood cell counts are extremely low, and the bone marrow appears empty. The pathophysiology of aplastic anemia is now believed to be immune-mediated, with active destruction of blood-forming cells by lymphocytes. The aberrant immune response may be triggered by environmental exposures, such as to chemicals and drugs or viral infections and, perhaps, endogenous antigens generated by genetically altered bone marrow cells. In patients with post-hepatitis aplastic anemia, antibodies to the known hepatitis viruses are absent; the unknown infectious agent may be more common in developing countries, where aplastic anemia occurs more frequently than it does in the West.
The syndrome paroxysmal nocturnal hemoglobinuria (PNH) is intimately related to aplastic anemia because many patients with bone marrow failure have an increased population of abnormal cells. In PNH, an entire class of proteins is not displayed on the cell surface because of an acquired X-chromosome gene mutation. The PNH cells may have a selective advantage in resisting immune attack. In contrast, the disease myelodysplasia can be confused with aplasia and can also evolve from aplastic anemia. The occurrence of cytogenetic abnormalities in patients years after presentation implies that genomic instability is a feature of this immune-mediated disease.
Aplastic anemia can be effectively treated by stem-cell transplantation or immunosuppressive therapy. Transplantation is curative but is best used for younger patients who have histocompatible sibling donors. Antithymocyte globulin and cyclosporine restore hematopoiesis in approximately two thirds of patients. However, recovery of blood cell count is often incomplete, recurrent pancytopenia requires retreatment, and some patients develop late complications (especially myelodysplasia).
Venn diagram showing possible relationships among bone marrow failure syndromes.
Table. Drugs Associated with Aplastic Anemia in the International Aplastic Anemia Agranulocytosis Study
Pathophysiology and treatment of aplastic anemia.GVHD
Results of treatment in patients with acquired aplastic anemia. A.BC
The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.
Young NS. Acquired Aplastic Anemia. Ann Intern Med. 2002;136:534–546. doi: https://doi.org/10.7326/0003-4819-136-7-200204020-00011
Download citation file:
Published: Ann Intern Med. 2002;136(7):534-546.
Hematology/Oncology, Red Cell Disorders, Updates.
Results provided by:
Copyright © 2019 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use