title: Effects of prothrombin complex concentrate and recombinant activated factor VII on vitamin K antagonist induced anticoagulation.
abstract: BACKGROUND
  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.
  
  
  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 mug 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 mug/ml). The treatments were evaluated using prothrombin time (PT) and thrombin generation (Thrombinoscope).
  
  
  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.
  
  
  CONCLUSIONS
  Both PCC and rFVIIa reverse warfarin anticoagulation based on PT, but only PCC restores overall thrombin generation.
authors.affiliation: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, USA. kenichi.tanaka@emoryhealthcare.org
authors.forename: Kenichi A
authors.initials: KA
authors.lastname: Tanaka
authors.forename: Fania
authors.initials: F
authors.lastname: Szlam
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dickneite
authors.forename: Jerrold H
authors.initials: JH
authors.lastname: Levy
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D015942:Factor VIIa / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019934:International Normalized Ratio; D023421:Models, Animal; D011516:Prothrombin / Q000187:drug effects / Q000502:physiology*; D011517:Prothrombin Time; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013917:Thrombin / Q000187:drug effects / Q000378:metabolism; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D011994:Recombinant Proteins; D014812:Vitamin K; D014859:Warfarin; D011516:Prothrombin; D015942:Factor VIIa; D013917:Thrombin