Therapeutical Effects of Heparin and Aprotinin on Experimental Disseminated Intravascular Coagulation in the Rat

Bolus Injection ◽

Fibrinogen Level ◽

Isotonic Saline ◽

Plasma Fibrinogen Level ◽

Fibrin Deposition ◽

Fibrin Thrombi ◽

Fibrin Monomers

A disseminated intravascular coagulation (DIC) was induced in rats by injection of 1 mg endotoxin and subsequent infusion of isotonic saline (500 ml/kg/5 hours) over a period of 5 hours. Animals were treated beginning at the time of initial glomerular fibrin deposition with heparin (1000 IU/kg) or aprotinin (40000 KIU/kg) or heparin-aprotinin in combination (each drug as given as in single dose). The first half-dasc was given as an bolus injection 2 hours after the endotoxin injection, the second dose immediately was added to the saline infusion. The extent of DIC was controlled by several blocdparameters, histological examination of the kidneys, and by the application of 125–I-fibrinogen (given after starting DIC) and 131-I-fibrinogen (injected after beginning the therapy). By the use of two isotopes it was possible to observe the behaviour of the fibrinogen in two different phases.Heparin had clearly favorable effects stabilizing the situation of hemostasis, although the fibrinogen turnover was not normalised completely, probably due to fibrin monomers which even polymerize in presence of heparin. The beneficious effect of heparin was diminished by the addition of aprotinin which given alone had deleterious effects inhibiting the spontaneous removal of fibrin thrombi. The fibrinogen turnover was clearly enhanced supporting the concept that the plasma fibrinogen level cannot be protected by blocking the fibrinolysis which is very rarely generalized.

Effect of Vitamin E on Endotoxin-Induced Disseminated Intravascular Coagulation in Rats

10.1055/s-0038-1657264 ◽

1982 ◽

Vol 48 (02) ◽

pp. 235-237 ◽

Cited By ~ 14

Author(s):

T Yoshikawa ◽

Y Furukawa ◽

M Murakami ◽

K Watanabe ◽

M Kondo

Keyword(s):

Platelet Count ◽

Vitamin E ◽

Fibrinogen Level ◽

Degradation Products ◽

Tocopheryl Acetate ◽

Preventive Effect ◽

Fibrin Degradation Products ◽

SummaryExperimental disseminated intravascular coagulation (DIC) can be induced by 4 hr sustained infusion of endotoxin in a dose of 100 mg/kg in rats. The experimental model of DIC in rats was used to study the preventive effect of vitamin E, α-tocopheryl acetate, against DIC. Before the infusion of endotoxin, 0.01, 0.1, 1.0 or 10.0 mg/kg/day of α-tocopheryl acetate was injected intraperitoneally for 4 successive days. The preventive effect against DIC was noted in all the parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count, and the number of renal glomeruli with fibrin thrombi, in rats treated with 1.0 or 10.0 mg/kg of α-tocopheryl acetate. From these results, it was shown that vitamin E, α-tocopheryl acetate, inhibited endotoxin-induced experimental DIC in rats.

Effects of Ticlopidine and Aspirin on Endotoxin-Induced Disseminated Intravascular Coagulation in Rats

10.1055/s-0038-1657359 ◽

1983 ◽

Vol 49 (03) ◽

pp. 190-192 ◽

Cited By ~ 13

Author(s):

T Yoshikawa ◽

M Murakami ◽

Y Furukawa ◽

S Takemura ◽

M Kondo

Keyword(s):

Platelet Count ◽

Continuous Infusion ◽

Partial Thromboplastin Time ◽

Fibrinogen Level ◽

Degradation Products ◽

Preventive Effect ◽

Fibrin Degradation Products ◽

SummaryThe effects of ticlopidine and aspirin on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4 hr sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were intraperitoneally injected with ticlopidine at 2.0, 20.0, 50.0, 100.0 or 200.0 mg/kg, or aspirin at 0.03, 0.3, 3.0 or 30.0 mg/kg, followed by the continuous infusion of 100 mg/kg/4 hr of endotoxin. A preventive effect against DIC was noted in all the parameters, such as fibrinogen and fibrin degradation products (FDP), fibrinogen level, prothrombin time, partial thromboplastin time (PTT), platelet count and the number of renal glomeruli with fibrin thrombi, in the rats treated with 20.0, 50.0, 100.0 or mg/kg of ticlopidine. Although a preventive effect was also noted in FDP, PTT, platelet count and the number of glomeruli with thrombi in rats treated with 0.03 or 0.3 mg/kg of aspirin, this agent was less effective than ticlopidine.

Effects of Superoxide Dismutase and Catalase on Disseminated Intravascular Coagulation In Rats

10.1055/s-0038-1665331 ◽

1983 ◽

Vol 50 (04) ◽

pp. 869-872 ◽

Cited By ~ 28

Author(s):

T Yoshikawa ◽

M Murakami ◽

N Yoshida ◽

O Seto ◽

M Kondo

Keyword(s):

Superoxide Dismutase ◽

Platelet Count ◽

Fibrinogen Level ◽

Degradation Products ◽

Preventive Effect ◽

Endotoxin Infusion ◽

Fibrin Degradation Products ◽

SummaryThe effects of superoxide dismutase (SOD) and catalase on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4 hr sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were subcutaneously injected with SOD at 0.5, 5.0 or 50.0 mg/kg, or catalase at 0.01, 0.1 or 1.0 mg/kg, followed by the continuously infusion of 100 mg/kg/4hr of endotoxin. A preventive effect against DIC was noted in all the parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi, in the rats treated with 50.0 mg/kg of SOD or 1.0 mg/kg of catalase. When 50.0 mg/kg of SOD or 1.0 mg/kg of catalse was injected subcutaneously at 1, 2 or 3 hr after the initiation of the endotoxin-infusion, the protective effect against DIC was noted in all the parameters.

Studies in Experimental Animals on Disseminated Intravascular Coagulation (DIC)

10.1055/s-0038-1651410 ◽

1975 ◽

Vol 34 (02) ◽

pp. 513-521 ◽

Cited By ~ 10

Author(s):

F Markwardt ◽

G Nowak ◽

W Meerbach ◽

K.-D Rüdiger

Keyword(s):

Time Course ◽

Continuous Measurement ◽

Fibrinogen Level ◽

Consumption Coagulopathy ◽

Clotting System ◽

Experimental Animals ◽

Simultaneous Inhibition ◽

Fibrin Monomers

SummaryChanges in the clotting system, as well as morphological and functional alterations corresponding to that of the pathologic phenomenon of disseminated intravascular coagulation (DIC) or consumption coagulopathy, were produced by thrombin infusion (550 NIH U × kg−1 × h−1) in rats and simultaneous inhibition of fibrinolysis by PAMBA (100 mg/kg).Changes in the fibrinogen level and platelet count as well as the appearance of fibrin monomers and the formation of microthrombi in several organs were evaluated. Simultaneously, the function of the respiratory system was investigated by continuous measurement of oxygen consumption as well as elasticity and water content of the lung. From the time course of the alterations in the several parameters, conclusions can be drawn for the pathogenesis and the possible therapeutic influence on DIC.

Disseminated Intravascular Coagulation: A Clinical/Laboratory Correlation In 48 Patients

10.1055/s-0038-1653198 ◽

1981 ◽

Author(s):

R L Bick

Keyword(s):

Platelet Count ◽

Clinical Laboratory ◽

Fibrinogen Level ◽

Degradation Products ◽

Severe Bleeding ◽

Thrombin Time ◽

At Iii ◽

Pre Treatment

Disseminated intravascular coagulation (DIC) is a frequent clinical entity spanning from a moderately severe bleeding disorder to a catastrophic, fulminant, and often fatal form usually associated with hemorrhage or, less commonly,as diffuse thromboses. The clinical and laboratory features of DIC remain confusing and controversial. To critically evaluate the usefulness of coagulation tests in aiding in the diagnosis and monitoring of therapy in DIC the clinical and laboratory findings were summarized in 48 patients with DIC. All patients were subjected to a prothrombin time (PT), activated partial thromboplastin time (PTT), reptilase time (RT), thrombin time (TT), fibrin(ogen) degradation products (FDP), platelet count, protamine sulfate test (PSO4), fibrinogen determination, and biological antithrombin-III (AT-III) level at the time of diagnosis. In addition, these same laboratory modalities were used to monitor patients during and after therapy. In this series of 48 patients, 38 patients had acute DIC and 10 patients had chronic DIC. In those patients with acute DIC, 100% of patients presented with hemorrhage and 53% of patients had thrombosis; 26% of patients died of their DIC type syndrome. In those patients with chronic DIC, 100% presented with hemorrhage, 80% presented with thrombosis, and none died of their intravascular clotting process. The probability of a pre-treatment abnormality in acute DIC was: FDP > AT-III = platelet count PS04 > TT > PT > fibrinogen level > PTT > RT. The probability of pre-treatment abnormalties in chronic DIC was: FDP > PSO4 = PT > AT-III = RT platelet count fibrinogen level = TT. These studies suggest the FDP level, the AT-III level, PSO4, and fibrinogen level to be reliable for aiding in the diagnosis of acute DIC. In chronic DIC the fibrinogen level, PS04, PTT, and AT-III level appear to be the most reliable indicies.

Kidney Transplantation from Donors with Severe Disseminated Intravascular Coagulation

ISRN Transplantation ◽

10.5402/2013/646310 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 5

Author(s):

Lena Sibulesky ◽

Reginald Gohh ◽

Kevin Charpentier ◽

Paul Morrissey

Keyword(s):

Renal Dysfunction ◽

Organ Donor ◽

Machine Perfusion ◽

Tissue Plasminogen ◽

Successful Transplantation ◽

Organ Recovery ◽

The Brain ◽

Disseminated intravascular coagulation (DIC) is a syndrome characterized by massive formation of thrombin, which can lead to renal dysfunction or failure. Many transplant centers are reluctant to accept the kidneys from donors with DIC especially if renal dysfunction is present. We developed protocol of machine perfusion followed by tissue plasminogen activator (tPA) infusion in order to treat and evaluate DIC kidneys prior to transplantation. The kidneys were placed on machine preservation with tPA added to the perfusate prior to transplantation. Three kidneys were transplanted from two donors who sustained gunshot injuries to the brain. A biopsy at the time of organ recovery documented widespread fibrin thrombi in approximately 80% of the glomeruli. Serial biopsies showed interval improvement following machine perfusion and a normal appearing kidney three months after successful transplantation. The histological presence of DIC in a deceased organ donor, even if associated with renal dysfunction, is not a contraindication to renal transplantation. Machine perfusion and tPA infusions may contribute to the recovery and successful transplantation of such kidneys.

Effects of DX-9065a, an Orally Active, Newly Synthesized and Specific Inhibitor of Factor Xa, against Experimental Disseminated Intravascular Coagulation in Rats

10.1055/s-0038-1648877 ◽

1994 ◽

Vol 72 (03) ◽

pp. 393-396 ◽

Cited By ~ 25

Author(s):

Masahide Yamazaki ◽

Hidesaku Asakura ◽

Keiji Aoshima ◽

Masanori Saito ◽

Hiroshi Jokaji ◽

...

Keyword(s):

Degradation Products ◽

Specific Inhibitor ◽

Factor Xa ◽

Dose Finding ◽

Protective Effects ◽

Safety Studies ◽

Orally Active ◽

SummaryWe investigated the protective effects of DX-9065a, an orally active, newly synthesized and specific inhibitor of factor Xa, against two kinds of experimental disseminated intravascular coagulation (DIC) in rats. Endotoxin-induced experimental DIC was induced by a 4-h sustained infusion of endotoxin at a dose of 100 mg/kg. Thromboplastin-induced experimental DIC was induced by a bolus injection of thromboplastin at a dose of 150 mg/kg. The rats were orally administered DX-9065a at 10, 30 or 100 mg/kg 30 min before endotoxin or thromboplastin injection.In both DIC models, DX-9065a showed a protective effect against DIC, at all doses and in all parameters, including fibrin/fibrinogen degradation products (FDP), fibrinogen level, prothrombin time, activated partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi.When DX-9065a was orally administrated at 100 mg/kg without endotoxin or thromboplastin, no significant changes were seen in hemostatic parameters except PT and APTT, and no fibrin thrombi or abnormal bleeding were seen in renal specimens.These findings suggest that the new oral anti-Xa drug, DX-9065a, has an effect in reducing the severity of DIC. However, further dose-finding and safety studies of this drug have still to be assessed.

The Elimination of Labelled Fibrinogen in Galactosamine-Induced Experimental Hepatitis in Rabbits

10.1055/s-0039-1689512 ◽

1975 ◽

Author(s):

I. Mahn ◽

C. Reuter ◽

H. Merkel ◽

G. Müller-Berghaus

Keyword(s):

Liver Disease ◽

Intravenous Injection ◽

Isotonic Saline ◽

Coagulation Factors ◽

Virus Hepatitis ◽

Coagulation Defect ◽

Deutsche Forschungsgemeinschaft ◽

Glomerular Capillaries

The intravenous injection of D-galactosamine-HCl into animals induces a liver disease resembling virus hepatitis in man in its histological and clinico-phatological features. In a previous study disseminated intravascular coagulation was demonstrated by tracing fibrin-rich microdots in the renal glomerular capillaries, especially if the fibrinolytic system was inhibited by EACA (Thromb. Res. 1, 473, 1972). In order to differentiate between disturbance of synthesis and disseminated intravascular coagulation, investigations with 125I-fibrinogen were performed in rabbits treated with D-galactosamine (1 g/kg) and EACA (0.5 g/kg xhr). In rabbits infused with galactosamine and EACA the elimination of 125I-fibrinogen was increased in comparison to the control animals treated with EACA or isotonic saline only. If heparin (750 u/kg × hr) was infused additionally to galactosamine and EACA, the accelerated decay of labelled fibrinogen was prevented. The occurrence of 125I-activity in organs was pronounced in animals exhibiting microdot formation. These experiments indicate that due to a diminished synthesis of coagulation factors in this model of hepatitis disseminated intravascular coagulation may contribute to the coagulation defect.(Supported by the Deutsche Forschungsgemeinschaft, Bad Godesberg, Germany.)

Induction of disseminated intravascular coagulation by endotoxin and saline loading in rats II. Fibrin deposition and removal

Thrombosis Research ◽

10.1016/0049-3848(75)90123-1 ◽

1975 ◽

Vol 7 (1) ◽

pp. 47-58 ◽

Cited By ~ 3

Author(s):

Wolfram Theiss ◽

Peter Hilgard ◽

Heinrich Heyes

Keyword(s):

Fibrin Deposition ◽

Saline Loading

Ultramicronized Palmitoylethanolamide in the Management of Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation

International Journal of Molecular Sciences ◽

10.3390/ijms222111388 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11388

Author(s):

Ramona D’Amico ◽

Francesco Monaco ◽

Rosalba Siracusa ◽

Marika Cordaro ◽

Roberta Fusco ◽

...

Keyword(s):

Serine Proteases ◽

Lung Damage ◽

Bleeding Tendency ◽

Fibrin Deposition ◽

Severe Condition ◽

Lung Dysfunction ◽

Ultramicronized Palmitoylethanolamide ◽

Inflammatory Action

Disseminated intravascular coagulation (DIC) is a severe condition characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. In the last years, it represents one of the most frequent consequences of coronavirus disease 2019 (COVID-19). The pathogenesis of DIC is complex, with cross-talk between the coagulant and inflammatory pathways. The objective of this study is to investigate the anti-inflammatory action of ultramicronized palmitoylethanolamide (um-PEA) in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by continual infusion of LPS (30 mg/kg) for 4 h through the tail vein. Um-PEA (30 mg/kg) was given orally 30 min before and 1 h after the start of intravenous infusion of LPS. Results showed that um-PEA reduced alteration of coagulation markers, as well as proinflammatory cytokine release in plasma and lung samples, induced by LPS infusion. Furthermore, um-PEA also has the effect of preventing the formation of fibrin deposition and lung damage. Moreover, um-PEA was able to reduce the number of mast cells (MCs) and the release of its serine proteases, which are also necessary for SARS-CoV-2 infection. These results suggest that um-PEA could be considered as a potential therapeutic approach in the management of DIC and in clinical implications associated to coagulopathy and lung dysfunction, such as COVID-19.