Antithrombin III Treatment In Acute Liver Failure

1981 ◽  
Author(s):  
G E Vogel ◽  
P Bottennann ◽  
M v Clarmann ◽  
Ch Komm ◽  
A Oberdorfer
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Time Course ◽  
Antithrombin Iii ◽  
Liver Perfusion ◽  
Coagulation Factors ◽  
Average Dose ◽  
Intravascular Coagulation ◽  
At Iii ◽  
Coma Grade

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.

Factor II Related Antigen and Antithrombin III Levels as Indicators of Liver Failure in Consumption Coagulopathy

1982 ◽  
Vol 47 (03) ◽  
pp. 218-220 ◽  
Author(s):  
P Sié ◽  
E Letrenne ◽  
C Caranobe ◽  
M Genestal ◽  
B Cathala ◽  
...  
Keyword(s):  
Liver Failure ◽  
Antithrombin Iii ◽  
Coagulation Factors ◽  
Consumption Coagulopathy ◽  
Blood Coagulation Factors ◽  
Factor Ii ◽  
At Iii ◽  
Group A ◽  
Group B

SummaryIn order to detect impaired synthesis of blood coagulation factors associated to consumption coagulopathy, a simultaneous evaluation of factor II-related antigen (II rAg) and of antithrombin III (AT III) was carried out in 16 patients affected with severe defibrination. An in vitro preliminary study on plasma and serum demonstrated that the levels of II rAg and of AT III, assessed by the Laurell technique with Behring antisera, were not reduced by the coagulation process. The patients were, a posteriori, classified into two groups according to the absence (group A) or the presence (group B) of factors predisposing to liver failure such as metastasis, cirrhosis, and prolonged shock. II rAg and AT III levels are significantly correlated; they are in the normal range in group A but reduced in group B. Thus II rAg or AT III level determinations are useful markers in the detection of liver failure associated to the consumption phenomenon. These results also suggest that part of the decreased AT III levels reported in severe cases of disseminated intravascular coagulation may be the consequence of an associated liver failure.

scholarly journals Intravascular coagulation in acute liver failure in rats and its treatment with antithrombin III.

Gut ◽  
1988 ◽  
Vol 29 (8) ◽  
pp. 1103-1108 ◽  
Author(s):  
K Fujiwara ◽  
I Ogata ◽  
Y Ohta ◽  
K Hirata ◽  
Y Oka ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Antithrombin Iii ◽  
Intravascular Coagulation

Antithrombin III (AT-III) as a diagnostic aid in disseminated intravascular coagulation

1977 ◽  
Vol 10 (5) ◽  
pp. 721-729 ◽  
Author(s):  
Rodger L. Bick ◽  
Mildred L. Dukes ◽  
William L. Wilson ◽  
Lajos F. Fekete
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Antithrombin Iii ◽  
Diagnostic Aid ◽  
Intravascular Coagulation ◽  
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

Effect of Endotoxin on Kinetics of Antithrombin III

1979 ◽  
Author(s):  
H. Tanaka ◽  
N. Kobayashi ◽  
T. Takeuchi ◽  
M. Takada ◽  
T. Haekawa
Keyword(s):  
Half Life ◽  
Antithrombin Iii ◽  
Coagulation Factors ◽  
Synthesis Rate ◽  
Blood Samples ◽  
At Iii ◽  
Kinetics Of ◽  
Plasma Half Life

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.

scholarly journals Arginine residues are critical for the heparin-cofactor activity of antithrombin III

1985 ◽  
Vol 231 (1) ◽  
pp. 59-63 ◽  
Author(s):  
A M Jorgensen ◽  
C L Borders ◽  
W W Fish
Keyword(s):  
Time Course ◽  
Antithrombin Iii ◽  
Rapid Rate ◽  
Rapid Loss ◽  
Inhibitor Molecule ◽  
At Iii ◽  
Lysine Residues ◽  
Arginine Residues ◽  
Cofactor Activity

A dilution/quench technique was used to monitor the time course of chemical modification on the heparin-cofactor (a) and progressive thrombin-inhibitory (b) activities of human antithrombin III. Treatment of antithrombin III (AT III) with 2,4,6-trinitrobenzenesulphonate at pH 8.3 and 25 degrees C leads to the loss of (a) at 60-fold more rapid rate than the loss of (b). This is consistent with previous reports [Rosenberg & Damus (1973) J. Biol. Chem. 248, 6490-6505; Pecon & Blackburn (1984) J. Biol. Chem. 259, 935-938] that lysine residues are involved in the binding of heparin to AT III, but not in thrombin binding. Treatment of AT III with phenylglyoxal at pH 8.3 and 25 degrees C again leads to a more rapid loss of (a) than of (b), with the loss of the former proceeding at a 4-fold faster rate. The presence of heparin during modification with phenylglyoxal significantly decreases the rate of loss of (a). Full loss of (a) correlates with the modification of seven arginine residues per inhibitor molecule, whereas loss of (b) does not commence until approximately four arginine residues are modified and is complete upon the modification of approximately eleven arginine residues per inhibitor molecule. This suggests that (the) arginine residue(s) in AT III are involved in the binding of heparin in addition to the known role of Arg-393 at the thrombin-recognition site [Rosenberg & Damus (1973) J. Biol. Chem. 248, 6490-6505; Jörnvall, Fish & Björk (1979) FEBS Lett. 106, 358-362].

Kinetics Of Antithrombin III During Severe Consumption Coagulopathy In An Infant Measured Without Radioactive Tracer Proteins

1981 ◽  
Author(s):  
B Schmidt ◽  
U Wais ◽  
I Witt ◽  
W Pringsheim ◽  
W Künz
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Antithrombin Iii ◽  
Radioactive Tracer ◽  
Coagulation Factors ◽  
Turnover Rates ◽  
Intravascular Coagulation ◽  
Elimination Half ◽  
Coagulation Proteins ◽  
Precise Diagnosis ◽  
Severe Coagulopathy

The precise diagnosis of disseminated intravascular coagulation remains difficult to achieve: Decreased production of coagulation factors and/or thrombocytes can mimic the laboratory pattern of disseminated intravascular coagulation. The measurement of increased turnover rates for coagulation proteins would provide more convincing criteria.During the course of severe coagulopathy in an infant suffering from septicaemia and shock, antithrombin levels were determined repeatedly before and during treatment with Antithrombin concentrate: Activities and concentrations were measured, using chromogenic substrates and immunodiffusion plates, respectively. By mathematical analysis of these data, using a biexponential function, the plasma elimination half-life of the antithrombin III was estimated to be 7.5 to 10.5 hours. Compared with known plasma half-lives of radioactively labelled antithrombin III in adults, the increase was five- to ten-fold. This indicates an accelerated consumption of antithrombin III in this case of severe coagulopathy.

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