Causes of agranulocytosis in a hospital population: identification of dipyrone as an important causative agent.

A population of patients with agranulocytosis admitted to a general hospital over a period of 12 yr was studied retrospectively in order to determine the causes of the disease. Of the 48 cases identified, 31 (65%) had drug-induced neutropenia, whereas 17 (35%) had chronic neutropenia unrelated to the use of drugs. Eight patients had an underlying hematological malignancy. Patients with agranulocytosis not induced by drugs more frequently had hepatomegaly, splenomegaly, enlarged lymph glands, or thrombocytopenia together with severe anemia. In contrast, drug-induced agranulocytosis was more severe, with a higher incidence of positive blood cultures, low cellularity of initial bone marrow aspirates, and a shorter duration of neutropenia. Dipyrone and methimazole were the drugs most commonly associated with agranulocytosis. Dipyrone was probably the causative agent in two of the seven drug-induced fatalities. In view of these findings, and those of several previous reports, it is proposed that the use of dipyrone in Israel be severely restricted or discontinued altogether.