Antithrombin III (At III) In Acute Liver Failure (ALF): Experimental Data After Intoxications Of Dogs

Vogel, G., Bottermann, P. et al. [Verh. Dtsch. Ges. inn. Med. 85, 477 (1979)] observed a benefit therapeutical effect of AT III in patients with ALF. With respect to the fact that AT III has been used as one drug in a combination therapy the effect of AT III itself had still to be proven.

ALF was induced in Beagle-dogs by intoxications with carbon tetrachloride (CCl₄, 0.4 ml/kg, given orally over 2 days) and Galactosamine (Gain, 200 mg/kg, i. v.). First toxic symptoms were observed after 24 h: Elevated transaminases (GOT, GPT), alkaline phosphatase, serum bilirubin; the dogs developed severe coagulation disorders triggered by a DIC characterized by a fall of platelet counts and clotting factors AT III included. After Gain 5 of 6 untreated dogs died between 48 and 72 h. AT III concentrate prepared from human plasma (Behringwerke) and given i. v. in 3 different concentrations over a period of 3 days following intoxication reduced the toxicity: Associated with an inhibition of the consumption reaction there was a reduction of the death rate. The minimal effective dose was determined to be 3 × 50 U AT III/kg.

From the experimental data it can be concluded that AT III has a benefit effect on ALF. The results are in good agreement with the clinical observations by Vogel, Bottermann et al.