title: Prothrombin Complex Concentrate Is Effective in Treating the Anticoagulant Effects of Dabigatran in a Porcine Polytrauma Model.
abstract: BACKGROUND
  In the event of trauma, emergency reversal of anticoagulation therapy may be required. However, no specific reversal agents are routinely available for the direct oral anticoagulants such as dabigatran. The authors investigated four-factor prothrombin complex concentrate (PCC) for treating dabigatran-induced anticoagulation in a porcine polytrauma model.
  
  
  METHODS
  Dabigatran etexilate was given orally for 3 days and intravenously on day 4 to 32 pigs. Animals were randomized 1:1:1:1 to PCC (25, 50, or 100 U/kg) or saline. Study medication was administered 12 min after bilateral femur fractures and blunt liver injury. The primary endpoint was blood loss at 300 min.
  
  
  RESULTS
  The mean plasma concentration of dabigatran was 487 ± 161 ng/ml after intravenous administration. Blood loss was 3,855 ± 258 ml in controls and 3,588 ± 241 ml in the PCC25 group. In the PCC50 and PCC100 groups, blood loss was significantly lower: 1,749 ± 47 ml and 1,692 ± 97 ml, respectively. PCC50 and PCC100 effectively reduced dabigatran's effects on coagulation parameters, whereas control and (to a lesser extent) PCC25 animals developed severe coagulopathy. Sustained increases in endogenous thrombin potential occurred with PCC50 and PCC100.
  
  
  CONCLUSIONS
  Four-factor PCC (50 or 100 U/kg) is effective in reducing blood loss in dabigatran-anticoagulated pigs, but higher doses may induce a procoagulant state.
authors.affiliation: From the Departments of Anaesthesiology (M.H., R.R., O.G.) and Pathology (T.B.), RWTH Aachen University Hospital, Aachen, Germany; Department of CardioMetabolic Diseases Research, Boehringer Ingelheim GmbH & Co. KG, Biberach, Germany (J.v.R.); and Laboratory for Clinical Thrombosis and Haemostasis, Departments of Internal Medicine and Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands (H.t.C., H.M.H.S.).
authors.forename: Markus
authors.initials: M
authors.lastname: Honickel
authors.forename: Till
authors.initials: T
authors.lastname: Braunschweig
authors.forename: Joanne
authors.initials: J
authors.lastname: van Ryn
authors.forename: Hugo
authors.initials: H
authors.lastname: Ten Cate
authors.forename: Henri M H
authors.initials: HM
authors.lastname: Spronk
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Oliver
authors.initials: O
authors.lastname: Grottke
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D000069604:Dabigatran / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005269:Femur / Q000293:injuries; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D008099:Liver / Q000293:injuries; D008297:Male; D009104:Multiple Trauma / Q000150:complications*; D012965:Sodium Chloride / Q000008:administration & dosage; D013552:Swine
chemical_list: D000991:Antithrombins; D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D012965:Sodium Chloride; D000069604:Dabigatran