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.

Animals↗

PubMed1958

Alterations in the blood coagulation system induced by bacterial endotoxins. II. In vitro.

Bacterial endotoxins in vitro are capable of shortening the coagulation time of normal whole blood, native platelet-rich and platelet-poor plasma, and the blood of a hemophilic patient in silicone but not in glass. The point in the coagulation system at which the endotoxins act has not been found but the search has been narrowed by the demonstration that these materials act independently of leukocytes and red blood cells, and do not act as preformed thromboplastin or thrombin. The shortening of the coagulation time in vivo 4 hours after endotoxin injection is probably through a different mechanism than in vitro.

Blood Coagulation↗

PubMed1958

The prevention of the generalized Shwartzman reaction with sodium warfarin.

Using intravenous sodium warfarin, rabbits were rendered hypoprothrombinemic and subjected to two intravenous injections of Shear's polysaccharide. None of the 9 animals surviving the required period of time developed bilateral renal cortical necrosis or histologic thrombi in the kidney, liver, spleen, or lungs. In a control group of 7 animals treated only with endotoxin, 6 developed bilateral renal cortical necrosis. It is concluded that the prothrombin complex is necessary for the production of the generalized Shwartzman reaction by bacterial endotoxins and that this phenomenon is essentially a process of disseminated intravascular coagulation.

Animals↗