Effect of antithrombin III on experimental hepatotoxin poisoning in dogs

: Carbon tetrachloride (CCl4) produces hepatic necrosis and Galactosamine (GALN) causes acute hepatocellular injury in dogs. 8 Beagle dogs were treated orally twice with 0.4 ml/kg CCl4 and 12 Beagle dogs with 200 mg/kg GALN i.v. After intoxication, groups of dogs were given antithrombin III (AT III) (Kybernin) from human plasma (25-100 U/kg i.v., days 1-3). Serum enzymes (GOT, GPT) were elevated, alkaline phosphatase values and serum bilirubin were increased in all animals. Dogs developed severe coagulation disorders reflecting intravascular coagulation and depressed levels of factors produced by the liver, such as AT III or fibrinogen. First toxic symptoms were seen after 48 h. Untreated dogs died between 48 and 72 h after GALN. AT III reduced the toxic effects on the coagulation system dose-dependently (minimal effective dose 3 X 50 U/kg). Decrease of fibrinogen and of platelet count were less pronounced, coagulation tests (Quick, TEG) less altered than in untreated dogs. Death rate was reduced. In CCl4 intoxicated animals also serum enzyme levels normalized after AT III. In GALN treated animals serum glucose levels were decreased in control dogs. These experimental results confirmed clinical effects of AT III in acute hepatic intoxications of humans.