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.
Specific plasmatic concentrations of coagulation factors are necessary in endoscopic treatment e.g. slerosis of esophageal varices. Thrombotest of 35 to 40% is necessar. To correct with factor concentrates and fibrinogen is dangerous in cause of pushing DIC (disseminated intravascular coagulation). The substitution of the inhibitor AT III which is succeeded from prothrombin concentrates and fibrinogen avoid fearful consumption reactions. The AT III plasma activity was measured by chromogenic substrates in citric plasma. In 5 patients (2 female, 3 male- age 19-67) the diminished AT III-levels were increased to the normal value of 80%. After normalization of the inhibitors prothrombin complexes and if necessary fibrinogen were substituted. It was seen an assessable improvement of the plasmatic coagulation which depends on the unit concentration of the substituted factors. In the improved coagulation situation 2 laparoscopies and 3 slerosis of esophageal varices could be done without any bleeding complication.Patients with liver diseases and coagulation disorders who were unsuitable for endoscopic and surgical treatment can be treated with this concept.
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