Efficacy and safety of a prothrombin complex concentrate with two virus-inactivation steps in patients with severe liver damage.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of intravenous infusions of an improved prothrombin complex concentrate (PCC) formulation. PATIENTS AND METHODS: Twenty-two adults with haemostatic defects due to severe liver disease (Quick's test 50%), which required rapid haemostasis because of bleeding or before urgent surgery or invasive intervention. Laboratory follow-up, including the response and in-vivo recovery of the substituted coagulation factors II, VII, IX and X and protein C took place before, then 10 min, 30 min and 60 min after PCC substitution. Clinical efficacy (avoidance or cessation of bleeding) was assessed using a scale ranging from 'very good' to 'none'. RESULTS: Patients received a median PCC dose of 25.7 IU/kg. The response of factor IX and protein C was 1.2-1.4 (IU/dl)/(IU/kg), the in-vivo recovery was 49.7-57.4%, and the Quick's test increased from 39% to a maximum of 65%. Levels of activation markers of the coagulation system factor VIIa, prothrombin fragment 1 + 2 and thrombin antithrombin complex (TAT) increased, but without evidence of any thromboembolic events. Clinical efficacy was judged as 'very good' in 76% of patients after the first (n = 21) treatment. There were no changes in serological status regarding transmission of HIV, hepatitis A virus, hepatitis B virus and hepatitis C virus. No PCC-related adverse reactions occurred. CONCLUSIONS: The infusion of pasteurized, nanometre-filtered PCC is an effective, well-tolerated method of correcting prothrombin complex deficiency in patients with severe liver disease with haemorrhage, or before an urgent surgical or invasive diagnostic intervention.