Studies on the mechanism of synthesis and release of the procoagulant activity from leukaemic cells.

The synthesis and release of procoagulant activity (PCA) from leukaemic leucocytes was studied in an in vitro culture system stimulated by endotoxin. Puromycin, actinomycin-D, vinblastine, colchicine, dibutyryl cyclic AMP and ouabain were added to the culture system to study some of the metabolic processes of these cells in relation to synthesis and release of PCA. It was found that production of PCA is an active process and depends on new protein synthesis. The release of PCA from cells can be inhibited by vinblastine, an inhibitor of microfilament and microtubules in the cell. The optimal release of PCA occurs at pH 7.2-7.4 at 37 degrees C and is not inhibited by the ATPase inhibitor ouabain. Dibutyryl cyclic AMP inhibits the release/synthesis of PCA. Gram negative septicaemia and endotoxinaemia are capable of increased production and release of PCA from leukaemic cells and could contribute to the coagulation failure seen in this disease.