Studies on the Mechanism of the Shwartzman Phenomenon

Lee, Leung; Stetson, Chandler A.

doi:10.1084/jem.111.6.761

Cited by 31 publications

(1 citation statement)

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“…LEE [26] has shown that in the presence of reticuloendothelial blockage injection of antigen into specifically immunized rabbits or the infusion of soluble antigen-antibody complexes in normal rabbits will lead to the development of renal cortical necrosis. The fact that cross-reactive antibodies to endotoxins have been demonstrated in rabbit sera [39], and that other similarities have been described between the effects produced by endotoxins and by antigen-antibody complexes [30,41.42] offers the possibility that endotoxin may exert its effect on intravascular clotting by virtue of its antigenicity. Thus the endotoxin-induced Shwartzman phenomenon may be but one example of a broad biologic phenomeon having its origin in antigen-antibody reactions and its expression in intravascular clotting.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Aspects of Blood Coagulation in the Generalized Shwartzman Reaction: 1. Effects of Variation of Preparative and Provocative Doses of E. Coli Endotoxin

et al. 1967

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The generalized Shwartzman reaction (GSR) is induced in rabbits by two properly spaced intravenous injections of bacterial endotoxin and is characterized by the occurrence of bilateral renal cortical necrosis. This report describes the quantitative changes in the coagulation mechanism in response to variation of preparative and provocative doses of E. coli endotoxin and of the interval between injections. It also correlates the coagulation changes with the pathologic findings of renal cortical necrosis.Renal cortical necrosis was induced in 34 of 49 (70 %) of rabbits using 0.100 mg/kg of endotoxin as the preparative (first) injection and 0.200 mg/kg 24 hours later as the provocative (second) dose. Four hours after the preparative injection white blood cells and platelets fell significantly while fibrinogen, prothrombin time, and Factors V and VIII fell slightly. At 24 hours all determinants except the platelets had recovered and the white cells, Factor V and fibrinogen had risen to significantly higher levels than baseline. Following the second (provocative) injection of endotoxin, a precipitous fall in all factors occurred. Maximal changes developed two hours after the second injection for white cells and platelets and by four hours for the coagulation factors; at this time kidneys show fibrin. By 48 hours all factors except the platelets had returned to 24 hour levels (table I). Rabbits given 0.100 mg/kg of endotoxin and normal saline 24 hours later did not develop cortical necrosis of kidneys or reduction in levels of any of the coagulation factors or platelets (table 11).With 0.1 mg/kg of endotoxin as the preparative dose, the effect of variation in the provocative dose at 24 hours was studied. With 0.2, 0.1, 0.05 mg/kg provocation renal cortical necrosis was observed in 60-100 % of animals. Rabbits given 0.01 mg/kg of endotoxin, or saline, as the second injection did not develop the GSR. Coagulation changes were measured four hours after the provocative injections. With doses of endotoxin of 0.025 mg/kg and greater there was a significant fall in white cells, platelets and each of the coagulation factors measured. With 0.01 mg/kg there was a significant decrease in Factors 11, V and VIII but no significant fall in white cells, platelets or fibrinogen. With saline all of the measured factors rose (table V). Changes in fibrinogen following different provocative doses are demonstrated in fig. 5. Renal cortical necrosis did not occur until a fall in fibrinogen of 66 mg/100 ml was produced.The effect of varying the preparative dose was studied. Groups of rabbits were given either saline, 0.001 mg/kg, 0.01 mg/kg or 0.1 mg/kg endotoxin preparation and all animals received 0.1 mg/kg endotoxin 24 hours later. With saline or 0.001 mg/kg endotoxin as preparation no GSR occurred.

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Section: Discussionmentioning

confidence: 99%