title: Reversal of new, factor-specific oral anticoagulants by rFVIIa, prothrombin complex concentrate and activated prothrombin complex concentrate: a review of animal and human studies.
abstract: BACKGROUND
  Recombinant activated factor VII (rFVIIa), prothrombin complex concentrate (PCC) and activated PCC (aPCC) are three non-specific haemostatic agents sometimes employed to reverse new, factor-specific oral anticoagulants.
  
  
  METHODS
  We conducted a review in the literature to compare the abilities of rFVIIa, PCC and aPCC to reverse factor-specific anticoagulants. MEDLINE and EMBASE databases were searched up to Oct 2013.
  
  
  RESULTS
  Eleven animal studies and two human trials met predefined inclusion criteria. To account for dosing variations of anticoagulants among studies, data were interpreted based on standards referenced from human trials at therapeutic doses. In animal studies, inconsistencies in the reversal abilities of rFVIIa, PCC and aPCC can be partly attributed to inter-species differences in the affinity among various clotting factors and tissue factors. Moreover, the differences in the affinity between species-specific clotting factors and anticoagulants that were initially designed to inhibit human factor may impose additional obstacles when comparing single factor rFVIIa with agents that contained multiple clotting factors. In the absence of a common clinical indication for the utilization of rFVIIa, PCC and aPCC, it is difficult, if not impossible, to establish an equivalent dose among these haemostatic agents when comparing their effectiveness in reversing factor-specific oral anticoagulants. Human trials were too few and sub-optimally designed to draw definite conclusions.
  
  
  CONCLUSIONS
  While preclinical studies may hint at a role for these haemostatic agents in reversing the anticoagulant effects of oral, factor-specific anticoagulants, existing trials offer inconclusive evidence to guide a clinical decision among individual agents with respect to potency and thrombosis risk. The mechanistic differences of these hemostatic agents in terms of their interactions with other coagulation factors impose major obstacles for the scientists using animal models to compare the efficacy of these reversal agents.
authors.affiliation: Thrombosis & Atherosclerosis Research Institute (TAARI), McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Frank M H
authors.initials: FM
authors.lastname: Lee
authors.affiliation: Thrombosis & Atherosclerosis Research Institute (TAARI), McMaster University, Hamilton, Ontario, Canada; Division of Haematology-Oncology, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Anthony K C
authors.initials: AK
authors.lastname: Chan
authors.affiliation: Department of Pediatrics, The Hong Kong University Shenzhen Hospital, China.
authors.forename: Keith K
authors.initials: KK
authors.lastname: Lau
authors.affiliation: Thrombosis & Atherosclerosis Research Institute (TAARI), McMaster University, Hamilton, Ontario, Canada; Division of Haematology & Thromboembolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: chanh@mcmaster.ca.
authors.forename: Howard H
authors.initials: HH
authors.lastname: Chan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001779:Blood Coagulation Factors / Q000494:pharmacology*; D004347:Drug Interactions; D015942:Factor VIIa / Q000494:pharmacology*; D006801:Humans; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; C103587:recombinant FVIIa; D015942:Factor VIIa
keywords: anticoagulant; coagulation factor; factor VIIa; prothrombin complex concentrates