Severe aplastic anemia (SAA) is defined by a marrow cellularity of <25% and at least two of the following: (1) a neutrophil count <0.5×109/1; (2) a platelet count <20×109/1; and (3) a reticulocyte count <20×109/1 (SAA Working Party consensus conference). Very severe AA is defined by a neutrophil count of <0.2×109/1.
SAA is rare and in most patients the etiology is unknown (idiopathic SAA). Acquired SAA may be linked to ionizing radiation, chemicals (e.g., benzene), chemotherapeutic agents (International Agranulocytosis and Aplastic Anaemia Study, 1987; Yardley-Jones et al., 1991) or drugs that cause idiosyncratic marrow injury (e.g., gold, chloramphenicol, phenylbutazone and others). Occasionally SAA is associated with viral diseases such as nonA, nonB, nonC hepatitis, parvovirus (pure red cell aplasia) or Epstein–Barr virus and autoimmune disorders such as eosinophilic fasciitis (Fonseca and Tefferi, 1997).
The pathophysiology of SAA is incompletely understood and it is possible that there are various etiologies ultimately presenting as marrow failure. Defective hemopoietic stem cells, a defective marrow microenvironment, impairment of cellular interactions and immunological suppression of marrow function may be involved (Jandl, 1996). A role for autoimmune mechanisms is suggested by the therapeutic response to immunosuppressive treatment (Hathaway et al., 1967; Parkman et al., 1974), and by autologous recovery of marrow function following attempted allogeneic bone marrow transplantation or cyclophosphamide treatment without marrow infusion.