Antithrombin III Treatment In Acute Liver Failure

Abstract

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.

Early intervention with antithrombin III therapy to prevent progression of hepatic venoocclusive disease

“…Numerous animal models looking at the effects of antithrombin III on leukocyte infiltration and rolling have been described with the antithrombin III-treated group having a significant reduction in the inflammatory reaction when compared with controls [18,20]. The anti-inflammatory properties of antithrombin III in experimental models of sepsis, disseminated intravascular coagulation and allograft rejection have also been reported [17,21]. Antithrombin III has been shown to prevent microvascular leakage, to ameliorate ischemia reperfusion injury and to reduce leukocyte-endothelial interaction [17].…”

Clinical Evaluation of Antithrombin III Concentrate (BI 6.013) for Disseminated Intravascular Coagulation in Obstetrics

“…Recently some high-purity AT III concen trates were developed and have been suc cessfully used in DIC in combination with heparin [4][5][6].…”

Acute Liver Failure

“…It has been shown to transiently correct coagulopathy in patients with ALF and facilitate performance of invasive procedures; however, it should be used cautiously due to an increased risk of thrombosis. [110][111][112] Renal Failure in Acute Liver Failure…”