This report describes two patients who developed agranulocytosis while receiving prophylactic amodiaquine treatment. The neutrophil counts returned to normal in one after stopping the drug while the other died of sepsis. Amodiaquine-dependent circulating neutrophil IgG antibodies were demonstrated in both patients using the indirect granulocyte immunofluorescence test. The antineutrophil antibody activity was enhanced with the use of the major amodiaquine metabolite, mono-desethyl amodiaquine. Additional studies showed the activity of the sera to be nondialysable, heat stable, active against autologous as well as allogenic cells, and absent from the convalescent sera. There was no growth inhibition of allogenic myeloid committed progenitor cells (CFU-GM) following incubation with the patients' sera, complement and amodiaquine. These results indicate that agranulocytosis can be mediated by a drug-dependent antibody which affects mature blood cells.

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We prospectively studied the incidence of post-transfusion non-A, non-B hepatitis in 64 cardiac surgery patients: 4 (6.25%) developed non-A, non-B hepatitis after an incubation period of 4-10 weeks. Units of blood products from donors seropositive for antibody to hepatitis B core antigen (anti-HBc) were not associated with a greater risk of non-A, non-B hepatitis in recipients than units from seronegative donors. Our data indicate that donor blood anti-HBc testing is of no value as a screening method to reduce the incidence of post-transfusion non-A, non-B hepatitis.

Amodiaquine is used for antimalarial prophylaxis and treatment and has been associated with neutropenia and agranulocytosis in man. The effect of the drug on the in vitro growth of bone marrow human myeloid progenitor cells (GM-CFU) was tested using the soft agar culture technique: 42 haematologically normal subjects were studied and it was found that amodiaquine, at concentrations tested in vitro (0.005, 0.05 and 0.5 micrograms.ml-1), had no quantitative effect on the colony and cluster growth. Our results argue against direct toxicity of the drug on GM-CFU. Therefore, in cases of amodiaquine-associated neutropenia, alternative mechanisms should be considered: a abnormally sensitive GM-CFU; b) toxic effect of metabolites such as desethyl-amodiaquine; c) immune-mediated toxicity.

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