The influence of antithrombin III (AT III) substitution to supranormal activities on systemic procoagulant turnover in patients with end-stage chronic liver disease

Abstract

Objective: Since antithrombin III (AT III) substitution to normal activities could not be shown to have major beneficial effects in patients with end-stage chronic liver disease in a variety of clinical settings, we tested the hypothesis that substitution to supranormal activities decreases systemic procoagulant turnover better in this patient group.

Design: Controlled prospective clinical study.

Setting: Operating rooms at a University Hospital.

Patients: Twenty-four patients with histologically verified liver cirrhosis consecutively scheduled for liver transplantation.

Interventions: Nineteen patients were given an antithrombin III concentrate to achieve either 100% (n = 10) or 175% (n = 9) AT III activity. Control patients (n = 5) received saline 0.9% instead.

Measurements and results: Molecular markers of coagulation activation, platelet count and aggregability, and global coagulation variables were measured prior to AT III infusion and 60 min thereafter. In both AT III-treated groups thrombin-antithrombin III-complex increased significantly (p < 0.005), whereas prothrombin fragment F1 + 2, soluble fibrin and D-dimer concentrations, as well as other variables, did not show major changes.

Conclusions: Despite thrombin inhibition by AT III in patients with end-stage chronic liver disease, systemic procoagulant turnover was not significantly decreased 60 min after AT III application even to supranormal activities. Replenishment of the inhibitory antithrombin III pool, decreased in chronic liver disease, should not be expected to slow down the baseline consumptive component of the haemostatic disorder in this patient group.