title: Fibrinogen concentrate administration inhibits endogenous fibrinogen synthesis in pigs after traumatic hemorrhage.
abstract: BACKGROUND
  Fibrinogen plays a central role in coagulation and falls to critical levels early after trauma. Administration of fibrinogen concentrate (FC) to improve hemostasis after severe bleeding seems beneficial, but it is unclear whether its use introduces excessive fibrinogen with a potential risk of thrombosis. This study investigated changes of endogenous fibrinogen metabolism from FC administration following traumatic hemorrhage in pigs.
  
  
  METHODS
  Anesthetized, instrumented pigs were randomized into lactated Ringer's (LR) solution only and LR plus FC groups (n = 7 each). Femur fracture of each pig's left leg was followed by hemorrhage of 60% total blood volume and resuscitation with LR (3× bled volume, LR group) or LR plus FC at 250 mg/kg (LR-FC group). Afterward, a constant infusion of stable isotopes 1-C-phenylalanine (phe, 6 hours) and d5-phe (3 hours) was performed with hourly blood sampling and subsequent gas chromatography-mass spectrometry analysis to quantify fibrinogen synthesis and breakdown rates, respectively. Blood gas and coagulation indices (thromboelastography) were measured on intermittent blood samples, and hemodynamics was continuously monitored. Animals were euthanized after the 6-hour isotope period.
  
  
  RESULTS
  Mean arterial pressure decreased by 50% after hemorrhage but improved after LR resuscitation in both groups. Hemorrhage and LR resuscitation reduced total protein, hematocrit, fibrinogen, and platelets to 50% of baseline values. Moreover, hemorrhage and resuscitation decreased fibrinogen concentration (207 ± 6 vs. 132 ± 7 mg/dL) and clot strength (72 ± 2 vs. 63 ± 2 mm) in both groups (p < 0.05). FC administration restored plasma fibrinogen concentrations and clot strength within 15 minutes, while no changes occurred in the LR group. Fibrinogen synthesis rates in the LR-FC group (1.3 ± 0.2 mg/kg/h) decreased versus the LR group (3.1 ± 0.5; p < 0.05), whereas fibrinogen breakdown rates were similar.
  
  
  CONCLUSIONS
  Our data suggest an effective feedback mechanism that regulates host fibrinogen availability and thereby suggests that acute thrombosis from FC administration is an unlikely risk.
authors.affiliation: From the US Army Institute of Surgical Research, Fort Sam Houston, San Antonio, Texas.
authors.forename: Wenjun Z
authors.initials: WZ
authors.lastname: Martini
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dubick
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D001784:Blood Gas Analysis; D005264:Femoral Fractures / Q000150:complications; D005340:Fibrinogen / Q000008:administration & dosage* / Q000096:biosynthesis*; D008401:Gas Chromatography-Mass Spectrometry; D006439:Hemodynamics; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D006706:Homeostasis / Q000187:drug effects; D007552:Isotonic Solutions / Q000008:administration & dosage; D011897:Random Allocation; D013552:Swine
chemical_list: D007552:Isotonic Solutions; D005340:Fibrinogen