Effects of prothrombin complex concentrate and recombinant activated factor VII on vitamin K antagonist induced anticoagulation

Introduction: Warfarin and its derivatives are widely used for prevention of thrombotic incidents. Prothrombin complex concentrate (PCC) and recombinant activated factor VII (rFVIIa) have been used clinically for the acute reversal of this agent but there is a paucity of data on comparative efficacies of these hemostatic interventions. Materials and methods: Using in vivo rat and in vitro human models of anticoagulation, we compared PCC and rFVIIa on the recovery of endogenous thrombin generation. For in vivo reversal of anticoagulation, saline (control), PCC 50 U ml(-1), or rFVIIa100 mu g ml(-1) was given to rats which received phenprocoumon (2.5 mg kg(-1)) orally. For in vitro model, plasma samples from warfarin-treated individuals with INR values of 2.1-6.7 were spiked with PCC (0.2, 0.4, or 0.72 U ml(-1)) or rFVIIa (3.0 mu g/ ml). The treatments were evaluated using prothrombin time (PT) and thrombin generation (Thrombinoscope (TM)). Results: Administration of phenprocoumon to rats prolonged PT (14.7 +/- 0.5 to 50.43 +/- 0.7 s) and decreased peak thrombin generation by 89 +/- 2.3%. Administration of PCC dose dependently reversed the anticoagulation effects both in warfarin-treated human plasma and in phenprocoumon-treated rats by shortening PT and increasing peak thrombin levels. However, rFVIIa only reversed PT, but had minimal effects on peak thrombin levels. Conclusion: Both PCC and rFVIIa reverse warfarin anticoagulation based on PT, but only PCC restores overall thrombin generation. (C) 2007 Elsevier Ltd. All rights reserved.