Aplastic anemia is a condition of bone marrow failure that arises from suppression of, or injury to, the hematopoietic stem cell. The bone marrow becomes hypoplastic, fails to produce mature blood cells, and pancytopenia develops.
There are a number of causes of aplastic anemia (Table 13–10). Direct hematopoietic stem cell injury may be caused by radiation, chemotherapy, toxins, or pharmacologic agents. SLE may rarely cause suppression of the hematopoietic stem cell by an IgG autoantibody directed against it. However, the most common pathogenesis of aplastic anemia appears to be autoimmune suppression of hematopoiesis by a T-cell-mediated cellular mechanism, so-called idiopathic aplastic anemia. In some cases of idiopathic aplastic anemia, defects in maintenance of the hematopoietic stem cell telomere length (eg, dyskeratosis congenita) or in DNA repair pathways (eg, Fanconi anemia) have been identified and are likely linked to both the initiation of bone marrow failure and the propensity to later progress to myelodysplasia, PNH, or AML. Complex detrimental immune responses to viruses can also cause aplastic anemia.
Table 13–10.Causes of aplastic anemia. ||Download (.pdf) Table 13–10. Causes of aplastic anemia.
Autoimmune: idiopathic, SLE
Congenital: defects in telomere length maintenance or DNA repair (dyskeratosis congenita, Fanconi anemia, etc)
Toxins: benzene, toluene, insecticides
Medications: chloramphenicol, gold salts, sulfonamides, phenytoin, carbamazepine, quinacrine, tolbutamide
Post-viral hepatitis (viral agent known or unknown)
Non-hepatitis viruses (EBV, parvovirus, CMV, echovirus 3, others)
Paroxysmal nocturnal hemoglobinuria
Malignancy: large granular lymphocytic leukemia (T-LGL)
Patients come to medical attention because of the consequences of bone marrow failure. Anemia leads to symptoms of weakness and fatigue, neutropenia causes vulnerability to bacterial or fungal infections, and thrombocytopenia results in mucosal and skin bleeding. Physical examination may reveal signs of pallor, purpura, and petechiae (eFigure 13–18). Other abnormalities such as hepatosplenomegaly, lymphadenopathy, or bone tenderness should not be present, and their presence should lead to questioning the diagnosis.
Nonpalpable purpura. (Reproduced, with permission, from Bondi EE, Jegasothy BV, Lazarus GS [editors]. Dermatology: Diagnosis & Treatment. Originally published by Appleton & Lange. Copyright © 1991 by The McGraw-Hill Companies, Inc.)
The hallmark of aplastic anemia is pancytopenia (neutropenia, anemia, and thrombocytopenia). However, early in the evolution of aplastic anemia, only one or two cell lines may be reduced.
Anemia may be severe and is always associated with reticulocytopenia. RBC morphology is unremarkable, but there may be mild macrocytosis (increased MCV). Neutrophils ...