Drug induced aplastic anemia

Abstract

Experiences with 101 patients with aplastic anemia are reviewed with particular reference to diagnostic criteria, course, prognostic factors, treatment, and outcome. Aplastic anemia has been defined as that disease associated with pancytopenia, and a hypocellular bone marrow biopsy at some time in the course of the illness. Pancytopenia has been defined as a volume of packed red cells of less than 38 ml/100 ml, a total neutrophil count (polymorphonuclear plus bands and metamyelocytes) of less than 1800/cu mm, and a platelet count of less than 140,000/cu mm. Pancytopenia was observed in 83% of the patients on the initial examination, but, in all patients, later in the course of the illness. Leukopenia, monocytopenia, reticulocytopenia, and lymphopenia were observed, either initially or during the course of the illness, less frequently than anemia, neutropenia, and thrombocytopenia and were, therefore, of less diagnostic value. Generalized adenopathy and hepatomegaly were not features of the disease. Splenomegaly, up to but not more than 2 cm below the costal margin, was present in only 10% of the patients at the time of the initial examination. The disease was clearly drug induced in 51 patients, possibly drug induced in 19 patients, associated with solvents in 10, insecticides in 7, and of undetermined etiology in only 14. The onset of the disease was defined as the time of appearance of the first clinical manifestation. Bleeding, either alone or in combination with symptoms of anemia or infection, was the first sign of disease in 61 patients. The first clinical manifestation was related to anemia in 27 patients, and to infection in only five. The course of the aplastic anemia was the most variable feature of the disease, ranging from a fulminant course terminating in a few weeks to a chronic indolent course extending over as many as 15 yr. The course and outcome of the disease were determined primarily by the severity of the initial insult to the bone marrow as measured by the percentage of nonmyeloid cells in the initial bone marrow aspirate, the corrected reticulocyte count, and the total neutrophil count. These factors were of greater importance in determining the outcome of the disease than was the type of treatment employed. The studies failed to provide evidence that splenectomy, corticosteroid, or androgenic steroid therapy modified either the course or outcome of the disease.