Platelet and Fibrinogen Production: Relative Sensitivities to Endotoxin

Both the threshold, and possible mechanisms, for increased platelet and fibrinogen production after endotoxin were determined in male New Zealand rabbits. Animals received E. coli endotoxin (Difco, 026:B6) in single IV doses of 0.1, 0.5, 5.0, 10.0, or 50.0 μg/kg body mass. Selenomethionine-⁷⁵ Se (⁷⁵seM) was injected 18 h after endotoxin, and the percent incorporation into platelets and fibrinogen was used to measure thrombopoiesis and fibrinogen synthesis. Endotoxin was detected with the limulus test only in the blood of rabbits that had received 10.0 or 50.0 μg/kg. However, platelet production was increased after 0.5 μg/kg, the smallest endotoxin dose which caused significant reduction of platelet counts. Fibrinogen synthesis was increased after 5.0 μg/kg. An endotoxin dose of 50.0 μg/kg caused the greatest increase in ⁷⁵SeM-labeled platelets and fibrinogen (150% and 304%, respectively). Platelet counts were lowest at this dose; however, fibrinogen levels were not decreased nor were fibrin(ogen) degradation products detected. Therefore, stimulation of fibrinogen synthesis by endotoxin does not appear to be mediated through intial reduction of circulating fibrinogen levels. In contrast, a direct relationship was demonstrated among endotoxin dose, decrease in platelet count, and increase in production. The data suggest that endotoxin may alter platelet production by its effect on levels of circulating platelets.