Warfarin-reversal: results of a phase III study with pasteurised, nanofiltrated prothrombin complex concentrate

Abstract

Bleeding can be a major problem in patients on oral anticoagulation therapy. Beriplex P/N is a prothrombin complex concentrate (PCC) that has been developed for the rapid reversal of anticoagulation in patients requiring immediate haemostatic control. Beriplex P/N contains high concentrations of the coagulation factors II, VII, IX and X, together with the inhibitors protein C and protein S, and it can be rapidly prepared and administered at an infusion rate of up to 8.0 mL/min. The efficacy of Beriplex P/N in patients requiring emergency reversal of oral anticoagulation has been demonstrated in a prospective, open-label, uncontrolled study involving 43 patients; 17 with acute bleeding and 26 requiring emergency surgery. Beriplex P/N was administered at a dose of 25-50 IU/kg, according to baseline international normalised ratio (INR) in conjunction with vitamin K. Mean INR 30 minutes post-infusion was 1.18, and 93% of patients achieved an INR of <or=1.3. Clinical efficacy was rated as satisfactory or very good in 98% of patients. Therapy was found to be well tolerated. There were no adverse events related to the rapid rate of infusion and, of the 8 serious adverse events reported; only 1 was regarded as being possibly related to treatment. No virus transmission was observed and changes in thrombogenicity markers were found to be transient and did not correspond to any clinically observed thromboembolic events. In conclusion, Beriplex P/N is an effective and well-tolerated therapy for rapid, complete and predictable reversal of anticoagulation in patients with acute bleeding or requiring emergency surgery.