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Bone marrow was cultured in vitro for colonies of granulocytes and macrophages five months after a patient had recovered from amodiaquine induced agranulocytosis. The addition of amodiaquine, chloroquine, and sulfadoxine to the culture was followed by a dose dependent inhibition of colony growth in the patient's marrow but not in normal control bone marrow. Colony growth was, however, unaffected by proguanil, pyrimethamine, and quinine.These findings show that in vitro marrow culture may have important predictive value in some cases of drug induced agranulocytosis.Marrow culture-Five months after the agranulocytosis bone marrow was aspirated for in vitro culture of granulocyte and macrophage colonies in agar by the method of Pike and Robinson,2 with and without the addition of six antimalarial agents. A normal control marrow sample was cultured in parallel. Feeder layers were prepared from peripheral blood leucocytes from the patient and two healthy controls. Amodiaquine, chloroquine, proguanil, pyrimethamine, sulfadoxine, and quinine were each added in three different concentrations to bone marrow cells and incubated for one hour at 37'C before plating in duplicate. The drug concentrations were based on therapeutic plasma concentrations, the middle one approximating to peak blood values achieved in normal subjects after a single standard therapeutic dose (for example, for amodiaquine 200 mg). After 14 days cultures were scored by counting the numbers of colonies containing more than 40 cells. The normal range for our laboratory is 50-200 colonies/2 x 105 cells plated.

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SummaryAn inhibitor to clotting factor VIII (anti-VIII: C) developed in a 70 year old woman with carcinoma of the pancreas three months after palliative by-pass surgery. A life-threatening sublingual haemorrhage was controlled by infusion of human factor VIII concentrate in high dosage. With the objective of reducing pancreatic tumour size, combination cytotoxic therapy with fluorouracil and CCNU was given. Reduction in the size of the tumour was associated with disappearance of anti-VIII:C, reappearance of normal quantities of clotting factor VIII (VIII: C) in the plasma and resolution of the bleeding tendency. The anti-VIII: C was characterised as being predominantly of the IgG4 sub-class with k light chains. In vitro and in vivo studies showed the inactivation of VIII: C by anti-VIII: C was markedly non-linear. Normal quantities of factor VIII coagulant antigen (VIII: CAg) were detected in the patient’s plasma when VIII: C levels were negligible.