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


METHODS
Controlled prospective clinical study.


METHODS
Operating rooms at a University Hospital.


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


METHODS
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.


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.
Scherer
R
R
Klinik für Anästhesiologie und Intensivtherapie, Universitätsklinikum Charité-Virchow Berlin, Germany. rscherer@hu-berlin.de
Kabatnik
M
M
Erhard
J
J
Peters
J
J
D000328:Adult; D000990:Antithrombin III / Q000008:administration & dosage* / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D005340:Fibrinogen / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011446:Prospective Studies; D011517:Prothrombin Time; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage* / Q000378:metabolism
D015842:Serine Proteinase Inhibitors; D000990:Antithrombin III; D005340:Fibrinogen