Flavone acetic acid induces a coagulopathy in mice

Abstract

The effects of flavone acetic acid (FAA) on the coagulation properties of plasma from tumour-bearing and non-tumour-bearing mice have been investigated. The study was carried out primarily on CBA mice and the CaNT tumour, although substantiating data are included for two other tumours grown in the WH strain. FAA was injected at a range of single doses up to a maximum of 300 mg kg-1, and clotting properties of the plasma were measured in vitro at various times after FAA administration. Platelet numbers and the concentration of fibrin degradation products (FDP) in the plasma were also determined. Following a dose of 300 mg kg-1, the clotting times were significantly reduced at 15-30 min in both tumour-bearing and non-tumour-bearing mice of both strains. Detailed studies on coagulation in the CBA strain (+/- CaNT tumour) indicate that in tumour-bearing animals the initial decrease in clotting time is followed 4-6 h later by an increase in clotting time, thrombin time and FDP levels. Platelet counts of tumour-bearing mice also decreased significantly over this period. Similar experiments in non-tumour-bearing mice did not show these late effects. All the data from the coagulation tests on mice with CaNT tumours are consistent with the hypothesis that intravascular coagulation occurs following treatment with FAA, and that vascular occlusion in tumours, as a results of FAA-induced coagulopathy, may contribute to tumour regression.