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

1981 ◽  
Author(s):  
D Triantaphyllopoulos

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.

1984 ◽  
Vol 51 (02) ◽  
pp. 232-235 ◽  
Author(s):  
D C Triantaphyllopoulos

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.


1977 ◽  
Vol 10 (5) ◽  
pp. 721-729 ◽  
Author(s):  
Rodger L. Bick ◽  
Mildred L. Dukes ◽  
William L. Wilson ◽  
Lajos F. Fekete

1975 ◽  
Author(s):  
O. R. Ødegård ◽  
U. Abildgaard

Heparin cofactor activity and antithrombin III (At-III) activity measured with amidolytic methods; antifactor Xa by a clotting method (Biggs et al., Brit. J. Haemat. 19, 287, 1970) and immunoassay of At-III (Fagerhol & Abildgaard, Scand. J. Haemat. 7, 10, 1970) in plasma and serum showed:1) There was a close correlation between the plasma values as measured by all these methods (r = 0.84–0.93).2) The difference between plasma and serum values (“consumption”) was lower in warfarin treated and in haemophiliacs than in the other groups.3) The difference between plasma and serum was greater when measured by the heparin cofactor activity method than by the other methods. The reason for this discrepancy will be discussed. The results in different patient groups will be reported.4) As the heparin cofactor activity assay can be completed within 10 minutes after blood sampling, and has a higher precision than clotting assay and immuno assay, it is preferable for clinical use.


1979 ◽  
Author(s):  
H. Tanaka ◽  
N. Kobayashi ◽  
T. Takeuchi ◽  
M. Takada ◽  
T. Haekawa

The kinetics of antithrombin III(AT III) in dogs were studied using I-125-labelled AT III and Se-75-methionine. As reported at the last meeting of ISH, the plasma half-life of AT III was 1.7±0.2 days in normal 5 control dogs. The double i.v. administration of 200 ug/ltg of endotoxin and the single i.v. administration of 1 mg/kg of endotoxin resulted in 30% decrease of plasma AT III, 60% decrease of coagulation Factors (I, II, V, VII, VIII, IX), the shortening of plasma half-life of AT III to 1.4 days and the increase of J3u values, suggesting increase of the synthesis rate of AT III. Then, the synthesis of AT III was studied directly using Se-75-methionine. After i.v. injection of Se-75-methionine, blood samples were obtained. One ml of sample plasma was incubated for 24 hrs with 1 ml of anti-AT III antiserum, which was produied in rabbits and the radioactivity of the precipitates were determined. About 80% of AT III was recovered in the precipitates by this method. The maximum radioactivity was obtained 18 hrs after injection of Se-75-methionine, and 0.27 % of total injected Se-75-methionine were utilized to the production of AT III.These results indicates that; 1. Endotoxin accelerates the metabolism of AT III. 2. The analysis of AT III production is possible using Se-75-methionine as a tracer.


1998 ◽  
Vol 79 (1) ◽  
pp. 44-48
Author(s):  
H. A. Vinazzer

Antithrombin III (AT III) is the physiological inhibitor of a series of activated clotting factors. Its diminution increases the tendency of thromboembolism. In cases of acute DIC, AT III binds to thrombin and to other activated factors in circulation. Thereby both partners of the reaction become inactive. When by this mechanism the available biologic activity of AT III diminishes below about 50% of normal any further inactivation of active clotting enzymes is greatly inhibited. In such cases, the mechanism of DIC decompensates and the full symptoms of consumption coagulopathy develop. It was, therefore, obvious to attempt a substitution with concentrates of AT III in such cases. In different randomized trials it could be shown which effect AT III concentrates had on the outcome of Die. In these tests it could be clearly shown that repeated administration of AT HI concentrates in a dose that keeps AT III activity constantly around 100% had the following advantages over therapy with heparin. The duration of symptoms of DIC could be considerably shortened from an average of 120 h in the heparin group to 40 h in the AT HI substitution group. Furthermore, in most severe cases of acute consumption coagulopathy due to septic shock, the death rate could be considerably and highly significantly diminished in the patients who received AT III. Similar results were also found by different authors who were able to demonstrate that the average survival rate in patients with septic shock increased from 20% to over 70% when AT III was substituted. Key Words: Antithrombin IIIHeparinDiffuse intravascular coagulation.


Author(s):  
Abdulkerim Kasım Baltaci ◽  
Rasim Mogulkoc

Abstract Background Melatonin, an important neurohormone released from the pineal gland, is generally accepted to exercise an inhibitor effect on the thyroid gland. Zinc mediates the effects of many hormones and is found in the structure of numerous hormone receptors. Aim The present study aims to examine the effect of melatonin supplementation and pinealectomy on leptin, neuropeptide Y (NPY), melatonin and zinc levels in rats with hypothyroidism and hyperthyroidism. Methods This study was performed on the 70 male rats. Experimental animals in the study were grouped as follows: control (C); hypothyroidism (PTU); hypothyroidism + melatonin (PTU + M); hypothyroidism + pinealectomy (PTU + Pnx); hyperthyroidism (H); hyperthyroidism + melatonin (H + M) and hyperthyroidism + pinealectomy (H + Pnx). Blood samples collected at the end of 4-week procedures were analyzed to determine melatonin, leptin, NPY and zinc levels. Results It was found that thyroid parameters thyroid stimulating hormone (TSH), free triiodthyronine (FT3), free thyroxine (FT4), total T3 (TT3) and total T4 (TT4) decreased in hypothyroidism groups and increased in the groups with hyperthyroidism. The changes in these hormones remained unaffected by melatonin supplementation and pinealectomy. Melatonin levels rose in hyperthyroidism and fell in hypothyroidism. Leptin and NPY levels increased in both hypothyroidism and hyperthyroidism. Zinc levels, on the other hand, decreased in hypothyroidism and pinealectomy, but increased in hyperthyroidism. Conclusion The results of the study demonstrate that hypothyroidism and hyperthyroidism affect leptin, NPY, melatonin and zinc values in different ways in rats. However, melatonin supplementation and pinealectomy do not have any significant influence on the changes occurring in leptin, NPY and zinc levels in thyroid dysfunction.


Author(s):  
G E Vogel ◽  
P Bottennann ◽  
M v Clarmann ◽  
Ch Komm ◽  
A Oberdorfer

In acute liver failure (alf) there is a defect in synthesis of coagulation factors in addition there is a disseminated intravascular coagulation which is followed by an impairment of the microcirculation. With an early substitution of Antithrombin III (AT III) we tried to stop this situation. In 22 patients (10 female, 12 male, age 10-68) with alf presenting with hepatic coma (grade I-IV) we studied the time course of AT III plasma activity (the study started in December 1978 and is continued until now). AT III was measured with the chromogenic substrate method. When AT III activity fell below the level of 80% of normal, we started to substitute AT III and to give low dose heparin (125-500 U/hrs). In addition in case of bleeding or a decrease of coagulation factors or fibrinogen under the hemostatic active concentration, complexes of prothrombin and fibrinogen were administered. Besides the usual conservative treatment for alf, patients in coma (grade IV) were undergoing baboon liver perfusion. The rapid fall of the hepatic coagulation factors stopped. In patients, who still were able to synthesize coagulation factors a reincrease of these factors after administration of AT III was seen and there was a further fall in fibrinogen. The dosage of AT III in alf required to bring AT III to normal values depended on the degree of intravascular coagulation. The average dose in our study was 250 U/3 hrs. The clinical course of alf was prolonged in all patients and 7 patients with the prognostic deleterious colombindex (sum of factors II + V + VIII) < 75% eventually survived the alf. The coagulation disorders in alf can be treated with an early substitution of AT III; thus, there is more time for liver regeneration. Our results suggest an improved prognosis of the acute liver failure.


1977 ◽  
Author(s):  
R. Losito ◽  
D. Nathan ◽  
H. Gattiker ◽  
B. Longpré

It is known that various coagulation tests such as the thromboplastin generation test (TGT), thrombin generation (TG), levels of factor VIII or antithrombin III have been found to be abnormal in individuals with intravascular coagulation or having an increased tendancy to thrombosis. The aim of this study was to evaluate the role of the TGT, TG, factor VIII and antithrombin III assays in the diagnosis of possible mild intravascular coagulation in patients undergoing cardiac catheterization who had a history of smoking. In addition to these four tests, a routine coagulogram was performed for a total of 13 tests. It appeared that smokers had more abnormal tests (7.3/patient) than the controls (3.3/patient). The greatest association was between TGT and TG (29.6%) and TG and AT-III (25.9%). If by definition, hypercoagulability is present where 3 or more of these 4 mentioned tests were abnormal, then five patients were found to be in this category; all, except one, formed clots. In the patients (50) with a history of smoking, a third were found to have the TGT and the TG abnormal; however, the most striking observation in this group was in the antithrombin III where it was noted to be low in forty-five percent of the patients compared to the controls (patients having catheterization and were non-smokers) whose antithrombin III was found to be decreased in only five percent of the individuals. It is concluded that determination of antithrombin III may be of more importance in assisting the detection of hypercoagulability, especially in the smoking population, than the TGT, TG, or factor VIII.


1987 ◽  
Vol 58 (03) ◽  
pp. 884-887 ◽  
Author(s):  
Sandra G Lyon ◽  
Elliott C Lasser ◽  
Rosalyn Stein

SummaryA modification of an anti-Xa assay for plasma heparin has been devised using a low molecular weight dextran sulfate that competitively binds protein heparin neutralizers and displaces masked heparin. The addition of 0.12 mg dextran sulfate per ml of plasma permits heparin, neutralized by the products of platelet aggregation, to recover full functional activity against Xa. The assay will permit a more accurate assessment of both exogenous plasma heparin and endogenous liepaiin-like activity in blood samples collected with varying techniques. A further modification is proposed employing polybrene to neutralize the plasma heparin-like material providing a concurrent control for each sample that increases accuracy by eliminating the effect of varying AT-III levels which have anti-Xa activity.


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