title: [The effect of substitution with AT III- and PPSB-concentrates in patients with terminal liver insufficiency].
abstract: Patients with end-stage liver disease frequently develop combined coagulopathies due to increased procoagulant and fibrinolytic turnover as well as thrombocytopenia. The onset of clinical symptoms of a haemorrhagic diathesis requires balanced substitution of coagulation factors, since fresh frozen plasma alone does not always maintain a sufficient haemostatic potential in these patients. This substitution commonly follows standard rules based on the assumption that 0.5-1 IU of a coagulation factor or inhibitor concentrate given per kg body weight will increase its endogenous activity by 1%. We set out to investigate the validity of this standard regime in patients with end-stage liver disease scheduled for orthotopic liver transplantation.
  
  
  METHODS
  Fifty-one adult patients were prospectively studied. In 37 patients with antithrombin III (AT III) activity < 70%, an AT III preparation (Kybernin, Behring, Marburg, Germany) was given preoperatively (mean dose 2616 +/- 207 IU) following standard calculations in order to increase endogenous activity to 80%. Twenty-seven of the patients had chronic hepatic failure (CHF group) with histologically proven cirrhosis and 10 had acute hepatic failure (AHF group). Blood samples were drawn prior to a 15-min infusion of AT III concentrate and 30 min thereafter. In 14 patients with prothrombin time (PT) < 40%, AT III levels had been corrected earlier during the clinical course to achieve activities > 70%. Prothrombin complex (PPSB, Beriplex, Behring, Marburg, Germany) was substituted (mean dose 2304 +/- 289 IU) to increase procoagulant activity to PT > 60%. Blood samples were drawn in the same fashion as in the AT III group. The amounts of AT III and PPSB concentrates (delta AT III, [IU/kg]; delta PPSB [IU/kg]) required to increase AT III activity and PT, respectively, by 1% were calculated.
  
  
  RESULTS
  Standard calculations for AT III substitution indicated AT III recovery in all 37 patients who received AT III concentrate. However, there was a statistically significant difference between patients with CLF and ALF. In patients with CLF, delta AT III was found to be 0.8 IU/kg (+/- 0.1 SEM) and in those with ALF it was 1.5 IU/kg (+/- 0.1 SEM) (P < 0.05, t-test). In patients treated with PPSB concentrate, delta PPSB was 1.6 U/kg (+/- 0.2 SEM) for both CLF and ALF groups.
  
  
  CONCLUSIONS
  In patients with end-stage liver disease standard rules for substitution with AT III-concentrate are adequate only for patients with CLF. In patients with ALF higher AT III doses are required to achieve the expected effect on endogenous AT III activity. Procoagulant activity, as reflected by PT, can be increased by 1% when 1.6 IU/kg PPSB concentrate is given. However, this study shows the effects of coagulation concentrates only 30 min after administration. An increased volume of distribution and increased turnover may explain the poor recovery of AT III activity in the ALF group, indicating that the dose of coagulation concentrate should be estimated against the background of the patient's clinical symptoms and diagnosis.
authors.affiliation: Institut für Anästhesiologie, Universitätsklinikum, GHS Essen.
authors.forename: R
authors.initials: R
authors.lastname: Scherer
authors.forename: A
authors.initials: A
authors.lastname: Gille
authors.forename: J
authors.initials: J
authors.lastname: Erhard
authors.forename: D
authors.initials: D
authors.lastname: Paar
authors.forename: W J
authors.initials: WJ
authors.lastname: Kox
mesh_terms: D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D017093:Liver Failure / Q000188:drug therapy*; D017114:Liver Failure, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D000990:Antithrombin III
vernacular_title: Substitutionseffekt von AT III-und PPSB-Konzentraten bei Patienten mit terminaler Leberinsuffizienz.