title: Postinjury hyperfibrinogenemia compromises efficacy of heparin-based venous thromboembolism prophylaxis.
abstract: BACKGROUND
  Venous thromboembolism (VTE) prophylaxis remains debated following trauma, and recommendations have not been established. Although hyperfibrinogenemia is a marker of proinflammatory states, it also contributes to thrombus formation. Postinjury hyperfibrinogenemia is common, but the effect of hyperfibrinogenemia on VTE prophylaxis has not been fully elucidated. Therefore, we hypothesized that heparin is less effective for VTE prophylaxis following severe injury due to hyperfibrinogenemia.
  
  
  METHODS
  In vitro studies evaluated thromboelastography (TEG) parameters in 10 healthy volunteers after the addition of fibrinogen concentrate and heparin. Data from a recent randomized controlled trial, conducted at an academic level I trauma center surgical intensive care unit, were reviewed. Critically injured patients were randomized to standard VTE prophylaxis (5,000 U low-molecular-weight heparin daily) or TEG-guided prophylaxis (up to 10,000 U low-molecular-weight heparin daily) and were followed up for 5 days. Analysis was performed to evaluate the relationship between fibrinogen levels, measures of anticoagulation, and TEG parameters.
  
  
  RESULTS
  In vitro studies revealed increased fibrinogen reversed the effects of heparin as measured by TEG. Fifty patients were enrolled in the clinical study with 25 in each arm. Thromboelastography parameters, fibrinogen, platelet count, and anti-Xa levels did not differ between groups despite treatment provided. Fibrinogen levels increased over the 5-day study period (597 ± 24.0 to 689.3 ± 25.0), as well as clot strength (9.8 ± 0.4 to 14.5 ± 0.6), which had a significant correlation coefficient (P < 0.01). Moreover, there was a moderate inverse correlation between fibrinogen level and the effect of heparin (RF), which was significant on study days 1 and 3, implicating hyperfibrinogenemia in heparin resistance.
  
  
  CONCLUSIONS
  Hypercoagulability and heparin resistance are common following trauma. The preclinical and clinical relationships between fibrinogen levels and hypercoagulability implicate hyperfibrinogenemia as a potential factor in heparin resistance.
authors.affiliation: *Department of Surgery, University of Colorado Denver, Aurora; †Department of Surgery, Denver Health Medical Center, Denver; ‡Trauma Research Center and §Department of Pediatrics, University of Colorado Denver, Aurora; and ∥Research Department, Bonfils Blood Center, Denver, Colorado.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Harr
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Chin
authors.forename: Arsen
authors.initials: A
authors.lastname: Ghasabyan
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gonzalez
authors.forename: Max V
authors.initials: MV
authors.lastname: Wohlauer
authors.forename: Angela
authors.initials: A
authors.lastname: Sauaia
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005340:Fibrinogen / Q000378:metabolism* / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D013916:Thrombelastography / Q000379:methods; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D014947:Wounds and Injuries / Q000097:blood / Q000150:complications*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D005340:Fibrinogen