title: Thrombin generation capacity of prothrombin complex concentrate in an in vitro dilutional model.
abstract: BACKGROUND
  The use of PCC for the treatment of trauma-induced coagulopathy potentially increase the risk of thromboembolism and disseminated intravascular coagulation, which is addressed to an imbalance of both pro- and anticoagulants. As PCCs differ in composition, we used an in vitro dilutional approach to assess the overall thrombin generation of five different PCCs through various laboratory assays.
  
  
  METHODS
  The vitamin K-dependent coagulation factors, heparin, and antithrombin were assessed in five commercially available PCCs. The procoagulant potential of the PCCs was assessed in plasma and whole blood from 4 healthy donors by means of classical coagulation assays, thrombin generation assay and thromboelastometry. In order to reflect coagulopathy, whole blood was diluted to 80, 60, 40, and 20% with Ringer's lactate solution.
  
  
  RESULTS
  The five different PCCs were characterised by comparable levels of factors II, VII, IX and X (all around 20-30 IU/mL), whereas the heparin (0 to 17.6 IU/mL) and antithrombin (0.06 to 1.29 IU/mL) levels were remarkably different between manufactures. In vitro dilution of blood induced a prolongation of the PT and aPTT, and attenuation of thrombin generation and ExTem induced thromboelastometry. Overall, non- or low-heparin containing PCCs restored the in vitro dilutional coagulopathy, whereas PCCs containing heparin have an anticoagulant effect. The thrombin generation assay showed to be the most sensitive method for assessment of PCC effects.
  
  
  CONCLUSIONS
  This study shows that most available PCCs are not balanced regarding their pro- and anticoagulants. The effect of measured differences in thrombin generation among different PCCs requires further investigations to elaborate the clinical meaning of this finding in the treatment of trauma induced coagulopathy.
authors.affiliation: Department of Anesthesiology, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Grottke
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Henskens
authors.forename: Rene
authors.initials: R
authors.lastname: van Oerle
authors.forename: Hugo
authors.initials: H
authors.lastname: Ten Cate
authors.forename: Henri M H
authors.initials: HM
authors.lastname: Spronk
mesh_terms: D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000209:etiology; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001780:Blood Coagulation Tests; D006487:Hemostasis; D006801:Humans; D013917:Thrombin / Q000096:biosynthesis*; D014947:Wounds and Injuries / Q000150:complications
chemical_list: D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D013917:Thrombin