title: Increasing concentrations of prothrombin complex concentrate induce disseminated intravascular coagulation in a pig model of coagulopathy with blunt liver injury.
abstract: Despite increasing use of prothrombin complex concentrate (PCC) to treat hemorrhage-associated coagulopathy, few studies have investigated PCC in trauma, and there is a particular lack of safety data. This study was performed to evaluate PCC therapy in a porcine model of coagulopathy with blunt liver injury. Coagulopathy was induced in 27 anesthetized pigs by replacing approximately 70% blood volume with hydroxyethyl starch 130/0.4 and Ringer's lactate solution; erythrocytes were collected and retransfused. Ten minutes after trauma, animals randomly received PCC (35 or 50 IU/kg) or saline. Coagulation parameters including thromboelastometry, thrombin generation, and blood loss were monitored for 2 hours. Internal organs were examined macroscopically and histologically to determine the presence of emboli and assess liver injury. Total blood loss was significantly lower and survival was higher in both PCC groups versus the control group (P < .05). These outcomes appeared to be dose-independent. Thromboembolism was found in all animals treated with 50 IU/kg PCC; 44% also showed signs of disseminated intravascular coagulation. Liver injury was similar in all animals. In conclusion, 35 IU/kg PCC safely improved coagulation and attenuated blood loss. However, the higher dose of PCC (50 IU/kg) appeared to increase the risk of thromboembolism and disseminated intravascular coagulation.
authors.affiliation: Department of Anesthesiology, RWTH Aachen University Hospital, Aachen, Germany. ogrottke@ukaachen.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Grottke
authors.forename: Till
authors.initials: T
authors.lastname: Braunschweig
authors.forename: Henri M H
authors.initials: HM
authors.lastname: Spronk
authors.forename: Stephanie
authors.initials: S
authors.lastname: Esch
authors.forename: Annette D
authors.initials: AD
authors.lastname: Rieg
authors.forename: Rene
authors.initials: R
authors.lastname: van Oerle
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Christina
authors.initials: C
authors.lastname: Fitzner
authors.forename: Rene
authors.initials: R
authors.lastname: Tolba
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001780:Blood Coagulation Tests; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D008297:Male; D013552:Swine; D014949:Wounds, Nonpenetrating / Q000188:drug therapy* / Q000473:pathology
chemical_list: D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates