Abstract
A case of agranulocytosis is reported in which discovery of the offending drug was attempted by using the in vitro cloning technique.
A 45-year-old housewife presented with a 10-day history of fever and sore throat. She had received flurazepam and carbamazepin over the preceding period of three weeks. On examination she had a pyrexia of 38.6°C and necrotic ulcers in the buccal mucosa, palate and pharynx. The initial blood count revealed a WBC of 1.5×109/l with total absence of neutrophils, and bone marrow aspiration showed an entire lack of mature granulocytes. Flurazepam and carbamazepin were withdrawn, and a potent antibiotic chemotherapy was immediately started. Six days after the last dose of the drugs the neutrophils began to appear in the peripheral blood. Fever and sore throat subsided, and her blood findings returned to normal after a transient neutrophilia.
Influence of flurazepam and carbamazepin on the growth of granulocyte-macrophage progenitor cells (CFU-C) was investigated in the semisolid ager culture system. At a concentration comparable to that attained in vivo, flurazepam significantly suppressed CFU-C colony formation from the patient's marrow taken 10 months after the agranulocytic episode but not from a normal marrow with or without addition of the patient's serum to the culture system. Cluster formation either from the patient's or normal marrow was not inhibited by flurazepam. The result appears to indicate that the patient's bone marrow is susceptible to toxic action of this drug which affects progenitors younger than cluster forming cells. Carbamazepin was found not to be inhibitory on CFU-C in the patient's bone marrow.
