title: Fibrinogen concentrate in dilutional coagulopathy: a dose study in pigs.
abstract: Dilutional coagulopathy can be reversed with fibrinogen concentrate. Effects of different fibrinogen dosages on clot function are not defined; high doses may increase the risk of thromboemboembolism. This study investigated the effect of six fibrinogen dosages on coagulation profile and blood loss in coagulopathic pigs. Forty-two pigs underwent a 60% hemodilution (HD) with hydroxyethylstarch (HES 130/0.4). After a standardized bone injury, animals randomly received 37.5, 75, 150, 300, 450 or 600 mg/kg fibrinogen (FGTW, LFB) or 500 ml of saline. Four hours later, a standardized liver injury was performed. Animals were then observed for two hours or until death. Blood loss was measured after death; Hemodynamic and coagulation parameters (thromboelastometry) were measured at baseline (BL), after HD, 15', 1, 2, 4 hours after fibrinogen administration and 2 hours after liver injury or right before the animals' death. Occurrence of thrombosis was examined in histological slides of internal organs. Statistical significance was set at p < 0.05. Doses of 150 mg/kg fibrinogen and higher reversed dilutional coagulopathy: Maximum clot firmness (MCF) was decreased after hemodilution (36 ± 3 mm vs. 65 ± 4 mm at BL, p < 0.05) and returned to BL after fibrinogen administration (69 ± 5 mm). Blood loss was significantly decreased with increased fibrinogen dosages: 42 ± 19 (sham), 34 ± 14 (75 mg/kg), 29 ± 13 (150 mg/kg), 28 ± 10 ml/kgbw (600 mg/kg). Fibrinogen (150-600 mg/kg) normalized clot firmness and decreased blood loss. No signs of hypercoagulability or thromboembolism were detected after high dosages.
authors.affiliation: Clinical Department of Anesthesiology and General Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria; Clinical Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria; Department of Paediatrics, Medical University Innsbruck, Innsbruck, Austria; US Army Institute of Surgical Research, Fort Sam Houston, Texas.
authors.forename: Judith
authors.initials: J
authors.lastname: Martini
authors.forename: Sonja
authors.initials: S
authors.lastname: Maisch
authors.forename: Lisa
authors.initials: L
authors.lastname: Pilshofer
authors.forename: Werner
authors.initials: W
authors.lastname: Streif
authors.forename: Wenjun
authors.initials: W
authors.lastname: Martini
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fries
mesh_terms: D000818:Animals; D001778:Blood Coagulation Disorders / Q000097:blood / Q000188:drug therapy*; D001780:Blood Coagulation Tests; D001784:Blood Gas Analysis; D001842:Bone and Bones / Q000293:injuries; D004305:Dose-Response Relationship, Drug; D005260:Female; D005340:Fibrinogen / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D019106:Postoperative Hemorrhage / Q000473:pathology / Q000517:prevention & control; D034421:Sus scrofa
chemical_list: D005340:Fibrinogen