Mechanism of Aprindine Induced Agranulocytosis: Direct Toxicity on CFU-C and CFU-GEMM

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Abstract
The in vitro bone marrow growth of 2 patients with aprindine-induced agranulocytosis was studied. Granulocyte-macrophage committed stem cell (CFU-C) growth is inhibited by aprindine in a dose dependent manner. Inhibition (50%) of CFU-colony growth (TD50) was seen at 5.1 and 3.4 .mu.g aprindine/ml medium, respectively. The TD50 of control marrow CFU-C was 3.2 .mu.g/ml. Inhibition (100%) was seen at 16 .mu.g aprindine/ml, both in patients and controls. Pluripotential stem cell growth (CFU-GEMM) in control marrow was equally inhibited in a dose dependent manner by aprindine, though to a lesser extent (TD50: 9.1 .mu.g/ml), and with relative sparing of pure megakaryocyte and erythroid colonies. Coculturing of patients marrows with their respective acute phase serum did not inhibit CFU-C growth.