Effects of Human Antithrombin III on Mortality and Blood Coagulation Induced in Rabbits by Endotoxin

1984 ◽  
Vol 51 (02) ◽  
pp. 232-235 ◽  
Author(s):  
D C Triantaphyllopoulos
Keyword(s):  
Blood Coagulation ◽  
Bolus Dose ◽  
Antithrombin Iii ◽  
Coagulation Parameters ◽  
E Coli ◽  
At Iii ◽  
Baseline Values

SummaryTwenty-one rabbits were infused with 20μg/kg/hr of E. coli endotoxin for 6 hr. Eight of the animals were preinjected immediately before the infusion of endotoxin, with a bolus dose of human AT III calculated to increase the antithrombin content of the plasma by about 4 units/ml. All eight animals which were preinjected with AT III survived, while 5 of the 13 control rabbits infused with endotoxin alone died. The changes in coagulation parameters from the baseline values, between the 8 control rabbits which survived and the 8 animals which were preinjected with AT III were compared. The concentration of the preinjected human AT III declined significantly faster (P: <0.01) than that of the native rabbit AT III. AT III prevented the decline of F.XII throughout the infusion of the endotoxin. However, the decline in F.V, fibrinogen, prothrombin and platelets was not affected (P: >0.5) by the injection of AT III.

PROTEINASE-INHIBITOR COMPLEXES (PIC) IN SEPTIC AND NON-SEPTIC SHOCK. COAGULATION; LEUKOCYTE AND BACTERIAL PROTEASE INHIBITION BY MEANS OF PLASMA-INHIBITOR REPLACEMENT

1987 ◽  
Author(s):  
R Egbring ◽  
R Seitz ◽  
M Wolf ◽  
L Lerch ◽  
T Menges
Keyword(s):  
Antithrombin Iii ◽  
Coagulation Factors ◽  
In Vitro Models ◽  
Protease Inhibition ◽  
E Coli ◽  
Bacterial Protease ◽  
Bacterial Endotoxins ◽  
At Iii ◽  
Cardiac Shock

In septic or cardiac shock antithrombin III-thrombin (AT III-Thr) and a1antitrypsin-elastase(a1AT-ELP) as well as a2antiplas-min-plasmin (a2AP-Pl) are found to be elevated to different extents. In cardiac shock AT III-Thr is predominantly increased, while in septic disorders a2AT-ELP as indicator of leukocyte stimulation is additionally found to be elevated. Stimuli for leukocyte activation are bacterial endotoxins, immune complexes, factor Xlla and others. The possible action of bacterial proteases during septic infections is only known in animal models. To stop hemorrhagic complications in disseminated intravascular coagulation (DIC) following septic (n=24) or non-septic (n=15) shock, we treated the patients with AT III concentrate and FFP in relatively high amounts containing a2macroglobulin (a2M), a1antitrypsin (a1AT) and others which are not available as concentrates. Subsequent to the procedure PIC's decreased, coagulation factors and inhibitors as well as thrombocyte counts increased. In in vitro models bacterial proteases have been shown to destroy a1AT, activate prothrombin and others. Only a2M may inhibit proteolytic activity of Staph aureus, N. meningitidis, P. aeroginosa and K1. pneumoniae and E. coli as our in vitro studies, using fibrin plates containing a2M, demonstrated. Not only bleeding or microthrombotic complications might be influenced by plasma derivative substitution, but also proteases released from bacteria

On the Complex Formation of Antithrombin III with Thrombin

1973 ◽  
Vol 30 (02) ◽  
pp. 280-283 ◽  
Author(s):  
B Binder
Keyword(s):  
Complex Formation ◽  
Human Serum ◽  
Blood Coagulation ◽  
Antithrombin Iii ◽  
Normal Human Serum ◽  
Molecular Weights ◽  
At Iii ◽  
Normal Human

SummaryBased on gelfiltration studies, the part of AT III which becomes bound to thrombin during the process of in vitro blood coagulation was calculated to be about 40% of total AT III. Complexes consisting of one AT III and one thrombin molecule could not be detected while fractions corresponding to molecular weights of about 190,000 Dalton show AT III as well as thrombin activities. The AT III - thrombin complex in normal human serum consists, therefore, of either 2 AT III and 2 thrombin molecules or of one AT III and 4 thrombin molecules.

Effect of Heparin on Antithrombin III Activity During Delivery and Early Puerperium

1975 ◽  
Author(s):  
I. Rákóczi ◽  
B. Garadnay ◽  
L. Arnold ◽  
I. Gáti
Keyword(s):  
Pregnant Women ◽  
Blood Coagulation ◽  
Antithrombin Iii ◽  
Modified Method ◽  
Heparin Treatment ◽  
At Iii ◽  
Antithrombin Iii Activity

It is known that antithrombin III (AT III) is the main inhibitor of blood coagulation. It inactivates thrombin and activated × factor. Heparin increases the AT III activity in vitro as well as in vivo. The authors have studied the AT III activity in sera of 30 pregnant women, at term, before labour started (2–24 hrs) and 30 as well as 60 min after the birth of placenta and daily for five days after delivery. The AT III activity was determined using the modified method of Gerendas. Out of the 30 women 15 were given 5000 IU heparin subcutaneously 1½—2 hours before delivery. In the 15 women with no heparin treatment AT III activity of serum significantly decreased after birth of placenta compared with the predelivery value and became normal on the fifth postpartum day. Heparin given subcutaneously prevented development of this decrease.

Effect of High Plasma-Estrogen Level on Blood Coagulation Parameters

1979 ◽  
Author(s):  
H.C. Kim ◽  
E. Kemmann ◽  
R. Shelden ◽  
P. Saidi
Keyword(s):  
Factor Viii ◽  
Blood Coagulation ◽  
Antithrombin Iii ◽  
Fibrinogen Level ◽  
High Plasma ◽  
Base Line ◽  
Coagulation Parameters ◽  
Estrogen Level ◽  
Line Level ◽  
Gonadotropin Therapy

Administration of gonadotrophin (human FSH and LH) raises plasma estrogen level, while progesteron level remains unchanged. We studied the effect of high plasma estrogen level on the blood coagulation parameters. Coagulation parameters were measured on seven anovulatory women of ages between 26-33 years, who were undergoing daily gonadotropin therapy to induce an ovulation. Plasma 17-beta estradiol (E2) level increased 5 fold of base-line level during the treatment (fron 114 ± 28 pg/ml to 553 ± 217 pg/ml). Fibrinogen levels increased from 248 ± 38 mg% of base-line to 353 + 78 mg% during the treatment (t=3.17, P < .025). There was a significant positive correlation between E2 and fibrinogen level (r =.762, a=239.99, b=.23). However, there were no significant changes in prothrombin time (P.T.), activated partial thromboplastin time (A.P.T.T.), Factor VIII procoagulant activity (VIII. C), Factor VIII-related antigen (VIIIR:Ag), platelet retention by glass bead columns, or antithrombin III level during gonadotropin therapy. This study indicates that the acute endogenous rise of ovarian estrogen increases fibrinogen level, similar to pregnancy; but it does not have significant effect on the factorVIII-associated activities (FVIII:C & FVIIIR:Ag).

Blood Coagulation after Long Distance Running: Antithrombin III Prevents Fibrin Formation

1990 ◽  
Vol 63 (03) ◽  
pp. 430-434 ◽  
Author(s):  
Peter Bärtsch ◽  
André Haeberli ◽  
P Werner Straub
Keyword(s):  
Physical Exercise ◽  
Blood Coagulation ◽  
Antithrombin Iii ◽  
Degradation Products ◽  
Distance Running ◽  
Long Distance ◽  
Fibrin Formation ◽  
Long Distance Running ◽  
At Iii

SummaryPhysical exercise causes shortening of activated partial thromboplastin time (aPTT) and euglobulin clot lysis time. To investigate whether this activation of coagulation and fibrinolysis leads to in vivo thrombin or plasmin action after long distance running, 19 well trained male runners (36-65 years) were examined 5 to 53 min after termination of a 100 km race and 5 days later after at least 1 day without physical exercise. Compared to the control examination aPTT was decreased (30.2 ± 2.8 vs 35.3 ± 3.0 sec) and the following parameters were increased after the race: betathromboglobulin (40 ± 16 vs 23 ± 7 ng/ml), thrombin-antithrombin III (TAT) complexes (5.5 ± 3.4 vs 2.3 ± 0.7 pg/1), the fibrin(ogen) degradation products fragment E (57 ± 15 vs 35 ± 7 ng/ml) and B(3 15-42 (8.5 ± 2.5 vs 6.5 ± 2.5 ng/ml) (all p values <0.001). Platelet count, platelet factor 4, fibrinoepetide A (FPA) and haematocrit did not change significantly. Increased TAT complexes and unchanged FPA suggest that the generated thrombin was fully inactivated by antithrombin III (AT III) and did therefore not give rise to fibrin formation. The small increase of fibrin(ogen) degradation products indicates a minor in vivo activity of the fibrinolytic system. This investigation demonstrates the importance of AT III in the regulation of haemostasis in activated blood coagulation.

Endotoxin And Blood Coagulation In Patients With Traumatic- Haemorrhagic And Bacteriotoxic Shock

1981 ◽  
Author(s):  
A Stemberger ◽  
F Straßer ◽  
G Blüimel ◽  
B v Hundel shausen ◽  
S Jelen ◽  
...  
Keyword(s):  
Blood Coagulation ◽  
Antithrombin Iii ◽  
Degradation Products ◽  
Haemorrhagic Shock ◽  
Factor X ◽  
Septic Complications ◽  
Fibrin Degradation Products ◽  
Limulus Amoebocyte Lysate ◽  
Heat Treated ◽  
At Iii

Blood coagulation and fibrinolysis was carefully monitored in patients suffering from traumatic-haemorrhagic shock. Parameters like antithrombin III (AT III),factor X (IIa), plasminogen,fibrin degradation products, antiplasmin and fibronectin were measured. It could be demonstrated that a severe haemorrhagic shock correlated with an activated blood coagulation and stabilisation of circulation was followed by normalisation of blood coagulation.However in patients developping septic complications new disorders in blood coagulation were observed. The appearance of endotoxins was measured by a recently developped limulus amoebocyte lysate (LAL). Best results were obtained by diluting heat treated heparinized plasma samples followed by an incubation step with the X a substrate S-2222. Detection of less than 0.2 ng endotoxin/ml plasma could be achieved. The available data of 30 patients with traumatic-haemorrhagic and bacteriotoxic shock showed that the appearance of endotoxin mostly correlated with a decrease of AT III and fibronectin.In conclusion, AT III, fibronectin and endotoxin may serve as sensitive markers in the early diagnosis of sepsis.

Hemodialysis with Defibrotide: Effects on Coagulation Parameters

1992 ◽  
Vol 15 (10) ◽  
pp. 590-594 ◽  
Author(s):  
E. Filimberti ◽  
S. Cinotti ◽  
M. Salvadori ◽  
M. Amato ◽  
G. Longo ◽  
...  
Keyword(s):  
Crossover Study ◽  
Blood Coagulation ◽  
Adverse Reactions ◽  
Significant Rise ◽  
Antithrombotic Activity ◽  
Coagulation Parameters ◽  
Fibrin Formation ◽  
At Iii ◽  
Thrombin Activation ◽  
Uremic Patients

In a crossover study conducted with eight uremic patients maintained on hemodialysis, the Authors compared the effects of heparin (100 IU/kg at the start of dialysis) and defibrotide (400 mg at the start, repeated at 2 hours of ongoing dialysis) on the parameters of blood coagulation (VIII:C, AT III, TAT, PC antigen and activity, PS, and FPA), each being assessed before dialysis and at 2, 3 and 4 hours of the ongoing procedure. Heparin-assisted dialysis resulted in a significant rise of VIII:C and AT III; with defibrotide, instead, there was evidence of thrombin activation (increased FPA and TAT). PC levels were raised with both dialysis modalities; however, PC activity and PS levels were increased only in defibrotide-assisted dialysis. There were no adverse reactions or evidence of fibrin formation. These results confirm the antithrombotic activity of defibrotide in the course of dialysis and indicate that this action is independent of thrombin neutralization.

Evaluation Of Antithrombin III In The Prevention Of Intravascular Coagulation In The Rabbit

1981 ◽  
Author(s):  
D Triantaphyllopoulos
Keyword(s):  
Bolus Dose ◽  
Antithrombin Iii ◽  
The Other ◽  
Rabbit Brain ◽  
Marginal Vein ◽  
Blood Samples ◽  
Experimental Animals ◽  
Intravascular Coagulation ◽  
Maximum Period ◽  
At Iii

In order to find out whether antithrombin III (AT III) alone in the absence of heparin is able to inhibit intravascular coagulation, 21 rabbits were infused under anesthesia with 0.19 - 1.74 mg/kg body weight/minute of rabbit brain tissue factor (TF) through the marginal vein of the ear for a maximum period of 1.5 hour and served as controls. Another group of 5 animals was injected with a bolus dose of human AT III, obtained by affinity chromatography on heparin-Sepharose, which was calculated to raise the concentration of the inhibitor by about 3 International units/ ml. This was followed by the infusion of TF at the same rates as in the controls. Blood samples were obtained through a catheter inserted in the carotid artery starting before the infusion of TF. Of the 21 control animals, 9 survived, 2 died in about 2 minutes and 10 between 15 and 30 minutes. Of the 5 animals which were preinfused with AT III only one survived (1.5 hour); the other 4 died about 15 minutes after the beginning of the infusion. No significant differences were found between control and experimental animals regarding the decline in the platelet count and in the concentration of fibrinogen, prothrombin, AT III, factors VIII, V, X and thrombin activity. In conclusion, preinjection of AT III alone, without heparin, into rabbits does not alleviate the manifestations of disseminated intravascular coagulation which are induced by the infusion of TF.

Induction of Hypercoagulability Condition by Chronic Localized Cold Stress in Rabbits

1999 ◽  
Vol 81 (03) ◽  
pp. 449-455 ◽  
Author(s):  
Selina Khatun ◽  
Hossain Belayet ◽  
Naoki Tokunaga ◽  
Kazuhiro Sumimoto ◽  
Takao Kobayashi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cold Stress ◽  
Hepatic Blood Flow ◽  
Antithrombin Iii ◽  
Fibrin Deposition ◽  
Predisposing Factor ◽  
Coagulation Parameters ◽  
Induced Stress ◽  
Hemorrhagic Necrosis ◽  
At Iii

SummaryTo evaluate the effect of cold-induced stress on renal and hepatic blood flow and coagulation parameters, rabbits’ soles were exposed to ice pad (0° C). Renal and hepatic blood flow was measured after 1 h and 15 days of cold stress. Coagulation parameters (0, 8th and 15th days of stress) and histological studies were performed. Renal and hepatic blood flow was significantly reduced after cold-stress. Decreased platelet count, antithrombin III (AT III) activity, increased fibrinogen (Fbg) level, shortened activated partial thromboplastin time (aPTT) and prothrombin time (PT) was found after 8 and 15 days of cold-stress. Histology showed enlarged glomeruli with fibrin deposition in kidney, ischemic changes and fibrin deposition in liver and hemorrhagic necrosis in adrenal cortex. We conclude that undesirable localized cold induced sympathetic stimulation in daily life may be a predisposing factor for coagulopathy.

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