Alterations in the Blood Coagulation System Induced by Bacterial Endotoxin

McKay, Donald G.; Shapiro, Sandor S.

doi:10.1084/jem.107.3.353

Cited by 214 publications

(71 citation statements)

References 15 publications

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“…In about a fourth of the dogs a systemic coagulation disorder then developed, with abnormalities often associated with disseminated intravascular coagulation. [33][34][35] Similar trapping of antibodies, formed blood elements and clotting factors was documented in Case 1 after the transplantation of consecutive grafts from the same donor. Nevertheless, these kidneys were not destroyed immediately, possibly because the fibrinolysis that quickly developed had a protective effect.…”

Section: Discussionmentioning

confidence: 86%

Clotting Changes, Including Disseminated Intravascular Coagulation, during Rapid Renal-Homograft Rejection

Starzl¹,

Boehmig²,

Amemiya³

et al. 1970

N Engl J Med

116

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One of two patients in whom early homograft rejection developed after renal transplantation had many antidonor antibodies before operation. By the measurement of gradients across intracorporeal and extracorporeal homografts in this patient, the new kidneys were shown to sequester host immunoglobulins, platelets, white cells and clotting factors. Moreover, the renal venous blood then contained fibrinolytic activity. This presensitized recipient, as well as a second patient who did not have detectable preformed humoral antibodies, gave evidence from clinical observation and from the various clotting tests of disseminated intravascular coagulation with fibrinolysis and a severe bleeding, diathesis. Immunofluorescent and histologic studies revealed a laying down of fibrin in the homograft vessels that continued in some cases to cortical necrosis of the transplanted kidneys or, alternatively, receded at the time fibrinolysis occurred. The variety of rejection seen in these patients has been characterized as an immunologically induced coagulopathy.When a kidney homograft is revasculurized in a recipient who is presensitized to donor antigens there is a substantial risk of either accelerated or hyperacute rejection of the transplant. [1][2][3][4][5] The mechanism of the immediate destruction has been disputed. Two years ago in this journal, a clinical report from our institutions 5 suggested that an instantaneous antigen-antibody reaction or other mechanisms could precipitate a coagulopathy like that of the Shwartzman reaction and that the consequent fibrin thrombi could occlude the renal micro-vasculature and be responsible for cortical necrosis. The principal evidence in support of this contention was from special histologic examinations. Unfortunately, clotting assays were not obtained in these patients.A subsequent publication by Colman and Merrill and their associates confirmed that there were massive fibrin deposits in two human kidneys that had been hyperacutely rejected by apparently presensitized recipients. 6 However, no systemic clotting changes could be detected in either of their patients, nor was there an arteriovenous gradient of any of the measured coagulation factors across the kidney in the most completely studied of these cases. Because of the negative findings, there was no satisfactory explanation even for the local in intravascular coagulation that the authors postulated and no evidence whatever that there had been a systemic clotting disorder at any time. In contrast, studies from our laboratories have shown that noteworthy alterations in local or systemic coagulation regularly occur in presensitized dogs after the transplantation of the kidney, liver or spleen. 7 The same thing has been seen in two recently treated patients whose renal homografts failed promptly. In both these human recipients, studies obtained revealed consumption of clotting factors either within the kidney or systemically, as well as fibrinolysis and a bleeding diathesis. MethodsThe technics of renal transplantation a...

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Section: Discussionmentioning

confidence: 86%

Clotting Changes, Including Disseminated Intravascular Coagulation, during Rapid Renal-Homograft Rejection

Starzl¹,

Boehmig²,

Amemiya³

et al. 1970

N Engl J Med

116

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“…It is possible, therefore, that platelet antiserum may enable localization of platelets in glomerular capillaries and, in that way, provoke the generalized Shwartzman reaction. Evidence has been presented that platelets are importantly concerned with the initiation and/or acceleration of intravascular coagulation resulting in the changes characteristic of the generalized Shwartzman reaction (4,6,16,17). Furthermore, anticoagulation inhibits the generalized Shwartzman reaction (11,12).…”

Section: Discussionmentioning

confidence: 99%

“…Many of the agents used to provoke the generalized Shwartzman phenomenon accelerate coagulation (4)(5)(6)18). In in vitro studies (16)(17)(18), platelets are required for the demonstration of acceleration of eoagtflation.…”

Section: Discussionmentioning

confidence: 99%

Platelets and the Shwartzman Phenomenon

Levin

Cluff

1965

The Journal of Experimental Medicine

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Studies are reported on the effect of immunologically induced thrombocytopenia upon the local and generalized Shwartzman phenomena. Intravenous injection of antiplatelet serum to rabbits produced profound but transient thrombocytopenia unaccompanied by significant changes in circulating leucocytes. Platelet antiserum alone given to rabbits prepared with thorotrast produced renal lesions characteristic of the Shwartzman reaction. Thrombocytopenia induced by platelet antiserum did not inhibit the cutaneous hemorrhagic lesion of the local Shwartzman phenomenon produced by sequential injections of endotoxin intracutaneously and intravenously. The implications of these observations in the pathogenesis of the local cutaneous and generalized Shwartzman reaction are discussed.

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“…Maximal changes developed two hours after the second injection for the white blood cells and platelets and by 4 hours for the coagulation factors. At this time kidneys of animals developing cortical necrosis will begin to show fibrin [13,151. By 48 hours all factors, except the platelets, had returned to the 24-hour levels.…”

Section: A Coagulation Changes Over a 48-hour Period During The Evolmentioning

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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Alterations in the Blood Coagulation System Induced by Bacterial Endotoxin

Cited by 214 publications

References 15 publications

Clotting Changes, Including Disseminated Intravascular Coagulation, during Rapid Renal-Homograft Rejection

Clotting Changes, Including Disseminated Intravascular Coagulation, during Rapid Renal-Homograft Rejection

Platelets and the Shwartzman Phenomenon

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

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