The
intravenous injection of bacterial
endotoxins alter the coagulation system of rabbits' blood in vivo. Twenty-four hours after the first injection the
fibrinogen level rises to twice normal values. The second injection at this time causes a 30 to 40 per cent decrease in
fibrinogen content in 4 hours. Twenty hours later it again rises to twice normal values. A marked decrease in whole blood coagulation times in
silicone occurs 4 hours after both
injections but rises to normal values 24 hours following each injection. The circulating platelets drop from average levels of 300,000/c.mm. to 150,000/c.mm. after the first injection. The platelets remain at this low level and decrease to less than 100,000 after the second injection. During this time no fibrinolytic or fibrinogenolytic activity can be detected. Also, there is no significant change in the one stage prothrombin times or
antithrombin titres. The marked decrease in circulating
fibrinogen at the time when intracapillary thrombi are formed suggests that the "hyaline" thrombi of the generalized
Shwartzman reaction are composed, in part, of
fibrin. There appears to be a relationship between the level of circulating
fibrinogen at the time of injection of bacterial
endotoxin and the extent of the
thrombosis. The higher the preinjection
fibrinogen level, the more extensive is the
thrombosis. There is also a relationship between the amount of
fibrinogen loss and the extent of
thrombosis after the injection. The more extensive the
thrombosis the greater is the postinjection decrease in circulating
fibrinogen. A comparison between the response of the
hemostatic mechanism to
tissue thromboplastin and bacterial
endotoxin indicates that the latter acts in a unique manner and not by way of a simple "thromboplastic" activity. From the hematological standpoint, "preparation" for the generalized
Shwartzman reaction is accompanied by an increased circulating
fibrinogen,
leukocytosis, and
thrombocytopenia.