Hageman Factor Activity in Liquoid-Induced Consumption Coagulopathy

1971 ◽  
Vol 26 (01) ◽  
pp. 058-070 ◽  
Author(s):  
G Müller-Berghaus ◽  
H. G Lasch
Keyword(s):  
Intravenous Injection ◽  
Coumarin Derivative ◽  
Consumption Coagulopathy ◽  
Factor Activity ◽  
Hageman Factor ◽  
Platelet Counts ◽  
Shwartzman Reaction ◽  
Initial Drop ◽  
Glomerular Capillaries

Summary1. Consumption coagulopathy was induced by intravenous injection of Liquoid (sodium polyanetholsulfonate) into rabbits. Thirteen out of 21 animals injected with Liquoid showed fibrin formation in the renal glomerular capillaries characteristic of the generalized Shwartzman reaction. In these 13 animals, a pronounced drop in Hageman factor activity was observed in addition to a decrease in platelet counts and fibrinogen levels.2. The consumption coagulopathy induced by Liquoid could be prevented by pretreatment of the rabbits with phenprocoumon, a coumarin derivative. None of 21 rabbits pretreated by this anticoagulant and injected with Liquoid showed fibrin in the renal glomerular capillaries. Phenprocoumon pretreatment did not influence the decrease in platelet counts, but it did significantly diminish the drop in fibrinogen levels. Although disseminated intra vascular coagulation and the generalized Shwartzman reaction could be inhibited by phenprocoumon pretreatment, this anticoagulant could not prevent the initial drop in Hageman factor activity after Liquoid injection.3. Phenprocoumon did not influence the activity or synthesis of Hageman factor. As phenprocoumon pretreatment could not prevent the drop in Hageman factor activity after intravenous injection of Liquoid, it might be concluded that the Hageman factor is either consumed, directly inactivated or destroyed in the animals independent of the presence of the prothrombin complex. These findings support earlier studies which have shown that inhibition of Hageman factor activation in vivo can prevent the generalized Shwartzman reaction induced by Liquoid.

Consumption of Hageman Factor Activity in the Generalized Shwartzman Reaction Induced by Liquoid

1970 ◽  
Vol 23 (02) ◽  
pp. 386-404 ◽  
Author(s):  
G Müller-Berghaus ◽  
H. G Lasch
Keyword(s):  
Partial Thromboplastin Time ◽  
Lethal Dose ◽  
Control Group ◽  
Factor V ◽  
Consumption Coagulopathy ◽  
Factor Activity ◽  
Hageman Factor ◽  
Intravascular Coagulation ◽  
Shwartzman Reaction

SummaryThe role of Hageman factor in triggering intravascular coagulation has been studied in rabbits injected intravenously with Liquoid. Besides changes of coagulation parameters characteristic of consumption coagulopathy (e.g. decrease in platelet counts, fibrinogen levels, factor V activity), a pronounced drop in Hageman factor activity was observed after injection of Liquoid. Likewise, the partial thromboplastin time became prolonged.The activation of Hageman factor in vivo could be prevented by intravenous infusion of lysozyme. Twenty min after starting the lysozyme infusion, the partial thromboplastin time became prolonged from a mean of 29 sec to 108 sec. Animals infused with lysozyme and injected with a lethal dose of Liquoid did not develop a consumption coagulopathy. In the same manner, none of 10 animals treated with lysozyme developed the generalized Shwartzman reaction, whereas in the control group 19 out of 20 animals showed fibrin thrombi in the glomerular capillaries.From the present study it may be concluded that the intravascular coagulation process after intravenous injection of Liquoid is triggered by Hageman factor activation.

scholarly journals Prevention of the Generalized Shwartzman Reaction by Bradykinin and Prostaglandins

1977 ◽  
Author(s):  
J.G. Latour ◽  
C. Léger-Gauthier ◽  
C. Groulx
Keyword(s):  
Single Injection ◽  
The Other ◽  
Male Rat ◽  
Adrenergic Stimulation ◽  
Pregnant Rat ◽  
Hageman Factor ◽  
Slow Infusion ◽  
Shwartzman Reaction ◽  
The Sacrifice ◽  
Glomerular Capillaries

We have investigated, in the pregnant rat, the implications of Hageman factor and prekallikrein activation in the pathogenesis of the generalized Shwartzman reaction (GSR). We have found that unlike the hyperlipemia animal, the pregnant rat, which develops the GSR after a single injection of endotoxin (S. typhosa 0.4 mg) on day 20 of gestation, does not consume prekallikrein. Prekallikrein was estimated by measurement on TAME of the arginine esterase activity generated by kallikrein upon addition of active Hageman factor to the test plasma. Bradykinin triacetate (2 or 4 μg/kg/min.), prostaglandin (PG) E-, (0.3 μg/kg/min.), PGA2 (1.0 μg/kg/min.) or isoproterenol (0.66 μg/kg/min.) when given as a slow infusion over 4 hours, from the time of the endotoxin to the sacrifice of the animals, were found to prevent the GSR. On the other hand, aspirin (150 mg/kg) or propranolol (2 mg/kg) given before endotoxin enhance the incidence or severity of the GSR. Furthermore, aspirin markedly reduces the prevention generated by bradykinin infusion and to a less extent that of isoproterenol. Finally, indomethacin (7 mg/kg) given twice daily for 3 days sensitizes the male rat to the GSR, since a single injection of endotoxin triggers deposition of fibrin in the glomerular capillaries. It is concluded that bradykinin generates the release of PG’s and that together they prevent, like the α-adrenergic and the D-serotoninergic blocking agents and or like a β-adrenergic stimulation, the renal vasomotor reactions found necessary for the GSR. These results support the hypothesis that impairment of kinin generation may possibly account for the sensitization of the pregnant rat to the GSR.

scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1953 ◽  
Vol 97 (6) ◽  
pp. 871-888 ◽  
Author(s):  
Robert A. Good ◽  
Lewis Thomas
Keyword(s):  
Intravenous Injection ◽  
Essential Role ◽  
Vascular Occlusion ◽  
Lethal Effect ◽  
Intradermal Injection ◽  
Cortical Necrosis ◽  
Hemorrhagic Necrosis ◽  
Shwartzman Reaction ◽  
Previously Treated ◽  
Glomerular Capillaries

In order to explore the hypothesis that the occurrence of thrombosis of small blood vessels is an essential stage in the development of the local and generalized Shwartzman reactions, the effect of heparin was studied. Aqueous heparin, administered intravenously, and "depot" heparin, injected subcutaneously, prevented completely the occurrence of the local and generalized Shwartzman phenomena. The amounts of heparin required for protection were similar to the amounts required to produce sustained incoagulability of the blood of rabbits for a period of at least 4 hours. The local and generalized Shwartzman reactions were prevented when heparin was given at the time of provocation, but not when heparin was administered during the period of preparation. Heparin prevented the development of bilateral cortical necrosis of the kidneys following a single intravenous injection of meningococcal toxin in rabbits previously treated with cortisone or thorotrast. Hemorrhagic necrosis of the skin which follows an intradermal injection of toxin in thorotrast-treated rabbits was also prevented by heparin. Provocation of the dermal Shwartzman reaction with glycogen, saline suspension of rabbit liver, and human serum was prevented by treatment with heparin. Heparin itself, in the preparations and dosages used, had no consistent effect on either white blood cell or platelet counts. Heparin had no effect on the occurrence of polymorphonuclear leukopenia which follows an intravenous injection of meningococcal toxin. Treatment with heparin did not interfere with the lethal effect of single, large doses of meningococcus toxin. In animals in which bilateral cortical necrosis of the kidneys was prevented by heparin, occlusion of the glomerular capillaries by "fibrinoid" material did not occur. These observations support the concept that vascular occlusion plays an essential role in the development of the local and generalized Shwartzman reactions.

scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1955 ◽  
Vol 102 (3) ◽  
pp. 263-278 ◽  
Author(s):  
Lewis Thomas ◽  
Richard T. Smith ◽  
Richard von Korff
Keyword(s):  
Low Temperature ◽  
Intravenous Injection ◽  
Nitrogen Mustard ◽  
Molecular Size ◽  
Qualitative Change ◽  
Synthetic Polymer ◽  
Shwartzman Reaction ◽  
Synthetic Acid

An intravenous injection of sodium polyanethol sulfonate, a heparin-like synthetic polymer of large molecular size, into rabbits given endotoxin 2 hours previously, results in the abrupt disappearance from the circulating blood of a large proportion of fibrinogen. The depletion of circulating fibrinogen is prevented by the administration of heparin prior to the synthetic polymer. In animals receiving the polymer alone, or endotoxin alone, no depletion of fibrinogen occurs. It is suggested that the intravascular deposition of fibrinoid and the subsequent necrotizing lesions of the generalized Shwartzman reaction, which occur after the combined injection of endotoxin and synthetic acid polymer, may be due to the intravascular precipitation of fibrinogen by polymer. A qualitative change in fibrinogen, characterized by its precipitability by heparin at low temperature, is regularly demonstrable in plasma between 1 and 4 hours after an intravenous injection of endotoxin. The appearance of this heparin-precipitable fraction is prevented by treatment with heparin before endotoxin. It is not influenced by nitrogen mustard or cortisone. During the period when depletion of circulating fibrinogen is produced by polyanethol, in endotoxin-treated animals, the heparin-precipitable fraction also disappears from the blood. It is suggested that the change in fibrinogen may represent partial polymertization, and the cold precipitability of this material by heparin may be related to its enhanced precipitability, in vivo, by polyanethol. An hypothesis which accounts for certain events in the generalized Shwartzman reaction, based on observations reported in this study, is presented.

scholarly journals ANTIGEN-ANTIBODY REACTION IN THE PATHOGENESIS OF BILATERAL RENAL CORTICAL NECROSIS

1963 ◽  
Vol 117 (3) ◽  
pp. 365-376 ◽  
Author(s):  
Leung Lee
Keyword(s):  
Immune Complexes ◽  
Coagulation System ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction ◽  
Soluble Immune Complexes ◽  
Antigen Antibody ◽  
Glomerular Capillaries

In the presence of reticuloendothelial blockade, the intravenous injection of a protein antigen into specifically immunized rabbits or the infusion of soluble immune complexes into normal animals has been shown to result in the production of bilateral renal cortical necrosis. The similarity in the pathogenesis of this lesion and that seen in the classical generalized Shwartzman reaction produced by bacterial endotoxins is indicated by (a) the failure of both lesions to develop in animals pretreated with large doses of heparin, (b) by the finding of "heparin-precipitable fibrinogen" in the circulation, and (c) by the presence of massive fibrin deposits within the glomerular capillaries. These findings indicate that antigen-antibody reactions in vivo are capable of activating the blood coagulation system and that the mode of action of bacterial endotoxins may have an immunological basis.

scholarly journals STUDIES OF THE EFFECT OF BACTERIAL ENDOTOXINS ON RABBIT LEUCOCYTES

1953 ◽  
Vol 98 (4) ◽  
pp. 331-348 ◽  
Author(s):  
Morgan Berthrong ◽  
Leighton E. Cluff
Keyword(s):  
Intravenous Injection ◽  
Inhibitory Effect ◽  
Buffy Coat ◽  
Single Intravenous Injection ◽  
Bacterial Endotoxins ◽  
Leucocyte Migration ◽  
Shwartzman Reaction ◽  
Local Shwartzman Reaction

Intravenous injection into rabbits of bacterial endotoxins results in an inhibition of migration of leucocytes from the buffy coat of their blood in tissue culture or in "slide cell" preparations. This effect was demonstrable 5 minutes after the intravenous injection and persisted for from 6 to 12 hours after the injection. It is as marked in rabbits receiving only a single intravenous injection of endotoxin as in those previously prepared intradermally and developing a severe local Shwartzman reaction on intravenous injection. The preparation of the skin for the Shwartzman reaction does not in itself result in appreciable changes of leucocyte migration. The production of the effect depends upon some action in vivo, since leucocytes of uninjected rabbits migrate normally from the buffy coat in plasma substrates to which large concentrations of endotoxin are added in vitro. The inhibitory effect, as observed in these experiments, also depends upon the added influence of centrifugation. Leucocytes from a rabbit receiving endotoxin intravenously migrate normally from uncentrifuged lung or spleen fragments and migrate normally in blood on the warm stage prior to centrifugation. Identical centrifugation does not affect leucocytes from uninjected animals. The heparin inhibition of the local Shwartzman reaction does not alter this effect of endotoxins on leucocytes. Its possible role in the production of leucopenia and of the local Shwartzman reaction is briefly discussed.

Liquoid Induced Stasis and the Generalized Shwartzman Reaction

1979 ◽  
Vol 41 (04) ◽  
pp. 804-810 ◽  
Author(s):  
Knut Nordstoga
Keyword(s):  
Red Cells ◽  
Renal Lesions ◽  
Intravenous Injections ◽  
Shwartzman Reaction ◽  
Glomerular Capillaries

SummaryThe composition of the occlusive material within dilated glomerular capillaries, following intravenous injections of Liquoid in blue foxes, was studied electron microscopically; it was found that it mainly consisted of a debris in which disintegrated red cells constituted the major component. Damaged platelets and necrotic endothelial remnants were other components. These observations were interpreted as a result of glomerular stasis, and it was concluded that stasis in glomerular capillaries is a basic event in the development of the renal lesions accompanying the generalized Shwartzman reaction.

The Glycosaminoglycan of Recombinant Human Soluble Thrombomodulin Affects Antithrombotic Activity in a Rat Model of Tissue Factor-Induced Disseminated Intravascular Coagulation

1992 ◽  
Vol 67 (03) ◽  
pp. 366-370 ◽  
Author(s):  
Katsuhiko Nawa ◽  
Teru Itani ◽  
Mayumi Ono ◽  
Katsu-ichi Sakano ◽  
Yasumasa Marumoto ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Disseminated Intravascular Coagulation ◽  
Rat Model ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Soluble Thrombomodulin ◽  
Intravascular Coagulation ◽  
Platelet Counts ◽  
Recombinant Human Soluble Thrombomodulin

SummaryPrevious studies on recombinant human soluble thrombomodulin (rsTM) from Chinese hamster ovary cells revealed that rsTM was expressed as two proteins that differed functionally in vitro due to the presence (rsTMp) or absence (rsTMa) of chondroitin-4-sulfate. The current study evaluates the in vivo behavior of rsTM in rats and in a rat model of tissue factor-induced disseminated intravascular coagulation (DIC). rsTMp was more potent than rsTMa for prolongation of the activated partial thromboplastin time (APTT) and their in vivo half-lives determined by ELISA were 20 min for rsTMp and 5.0 h for rsTMa. Injection of a tissue factor suspension (5 mg/kg) resulted in DIC as judged by decreased platelet counts and fibrinogen concentrations, prolonged APTT, and increased fibrin and fibrinogen degradation products (FDP) levels. A bolus injection of either rsTM (0.2 mg/kg) 1 min before induction of DIC essentially neutralized effects on platelets, fibrinogen, and FDP levels, and had only a moderate effect on APTT prolongation. The dose of anticoagulant to inhibit the drop in platelet counts by 50% (ED50) was 0.2 mg/kg rsTMa, 0.07 mg/kg rsTMp, and 7 U/ kg heparin. The effect of increasing concentrations of rsTM and heparin on bleeding times were compared in experiments involving incision of the rat tail. Doubling of the bleeding times occurred at 5 mg/kg rsTMa, 3 mg/kg rsTMp or 90 U/kg heparin. These values represent a 25-fold increase over the ED50 for rsTMa, 43-fold for rsTMp and 13-fold for heparin. These results suggest that rsTMp is a potent anticoagulant to inhibit the platelet reduction when injected prior to the induction of DIC in rats.

Effects of Ellagic Acid upon the Rabbit Fibrinolytic System

1972 ◽  
Vol 27 (01) ◽  
pp. 063-071
Author(s):  
S. G Iatridis ◽  
P. G Iatridis
Keyword(s):  
Continuous Infusion ◽  
Ellagic Acid ◽  
Animal Experimentation ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Clot Lysis ◽  
Hageman Factor ◽  
Lysis Activity ◽  
Site Of Action

SummaryThe present investigation deals with in vivo studies of possible relations of active Hageman factor (HFa) to the problems of thrombolysis. The study is based upon animal experimentation in which 40 normal, 5 dicumarolized and 5 heparinized rabbits each received ellagic acid (Elac 10-2 M) by intravenous continuous infusion at a rate of 1 ml/min for a period of 25 min. The data suggest that the Elac infusion induced in vivo activation of HF. Streptokinase (SK) injection 25 min from the start of Elac i. v. infusion failed to induce clot lysis in blood drawn one min after its injection. The phenomenon was more prominent with low (SK 250 U or 500 U) concentrations of SK. With higher concentrations, SK-induced clot lysis activity was not affected by Elac infusion.In dicumarolized and heparinized rabbits Elac infusion still counteracted the fibrinolysis activating effect of low concentration of SK. The possibility that the above described phenomenon was due to either hypercoagulability or to a non-specific inhibitory effect of Elac upon SK was explored and excluded.It is concluded that HFa and SK have the same site of action. Thus it seems that HFa may block the precursor upon which SK acts by forming a complex with it. It is stressed that activation of this precursor by HFa requires a suitable surface.

Turnover of Human Extrinsic (Tissue-Type) Plasminogen Activator in Rabbits

1981 ◽  
Vol 46 (03) ◽  
pp. 658-661 ◽  
Author(s):  
C Korninger ◽  
J M Stassen ◽  
D Collen
Keyword(s):  
Plasminogen Activator ◽  
Intravenous Injection ◽  
Active Site ◽  
Half Life ◽  
Degradation Products ◽  
Gel Filtration ◽  
Tissue Type ◽  
Organ Distribution ◽  
Small Rise

SummaryThe turnover of highly purified human extrinsic plasminogen activator (EPA) (one- and two-chain form) was studied in rabbits. Following intravenous injection, EPA-activity declined rapidly. The disappearance rate of EPA from the plasma could adequately be described by a single exponential term with a t ½ of approximately 2 min for both the one-chain and two-chain forms of EPA.The clearance and organ distribution of EPA was studied by using 125I-labeled preparations. Following intravenous injection of 125I-1abeled EPA the radioactivity disappeared rapidly from the plasma also with a t ½ of approximately 2 min down to a level of 15 to 20 percent, followed by a small rise of blood radioactivity. Gel filtration of serial samples revealed that the secondary increase of the radioactivity was due to the reappearance of radioactive breakdown products in the blood. Measurement of the organ distribution of 125I at different time intervals revealed that EPA was rapidly accumulated in the liver, followed by a release of degradation products in the blood.Experimental hepatectomy markedly prolonged the half-life of EPA in the blood. Blocking the active site histidine of EPA had no effect on the half-life of EPA in blood nor on the gel filtration patterns of 125I in serial plasma samples.It is concluded that human EPA is rapidly removed from the blood of rabbits by clearance and degradation in the liver. Recognition by the liver does not require a functional active site in the enzyme. Neutralization in plasma by protease inhibitors does not represent a significant pathway of EPA inactivation in vivo.

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