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Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis

Stanley L Schrier, MD
Section Editor
William C Mentzer, MD
Deputy Editor
Jennifer S Tirnauer, MD


Aplastic anemia (AA) is characterized by diminished or absent hematopoietic precursors in the bone marrow, most often due to injury to the pluripotent stem cell. The designation "aplastic anemia" is a misnomer because the disorder is defined as pancytopenia rather than anemia [1]. The disease is estimated to occur in two to four individuals per million population per year [1,2].

This topic will review the pathogenesis, etiology, clinical manifestations, diagnosis, and differential diagnosis of AA [3-5]. Prognosis and therapy are discussed separately. (See "Treatment of aplastic anemia in adults" and "Hematopoietic cell transplantation for aplastic anemia in adults".)


Following the atomic bombings in World War II, there was great interest in the effects of radiation. Lethally irradiated mice frequently died as a consequence of neutropenic infections and thrombocytopenic hemorrhage. Their marrow was found to be "aplastic." That is, the myeloid and erythroid precursors were absent, as were lymphocytes and megakaryocytes, leaving only fat cells, stromal elements, and blood vessels. Two striking observations in this model led to the discovery of the pluripotent hematopoietic stem cell, which could reconstitute all of hematopoiesis and lymphopoiesis:

The animals did not die if the spleen was exteriorized and shielded from irradiation [6]. Injection of a suspension of spleen cells could also minimize the pancytopenia and prevent death in lethally irradiated mice [7].

Injections of dilute suspensions of syngeneic bone marrow cells into lethally irradiated mice provided protection; in addition, microscopically visible colonies were present in the spleen (CFU-S) at 10 to 14 days [8]. Most of the colonies appeared to be purely erythroid or myeloid, although some were mixed. Injection of suspensions of "pure" differentiated colonies into lethally irradiated mice led to protection and reconstitution of hematopoiesis, with macroscopic spleen colonies showing the usual mix of "pure" and mixed lineages [9]. Experiments using karyotypic markers showed that each spleen colony was a clone (ie, derived from a single cell).


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Literature review current through: Jul 2017. | This topic last updated: Jun 12, 2017.
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