title: Fibrinogen concentrate in bleeding patients.
abstract: BACKGROUND
  Hypofibrinogenaemia is associated with increased morbidity and mortality, but the optimal treatment level, the use of preemptive treatment and the preferred source of fibrinogen remain disputed. Fibrinogen concentrate is increasingly used and recommended for bleeding with acquired haemostatic deficiencies in several countries, but evidence is lacking regarding indications, dosing, efficacy and safety.
  
  
  OBJECTIVE
  We assessed the benefits and harms of fibrinogen concentrate compared with placebo or usual treatment for bleeding patients.
  
  
  METHODS
  We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8); MEDLINE (1950 to 9 August 2013); EMBASE (1980 to 9 August 2013); International Web of Science (1964 to 9 August 2013); CINAHL (1980 to 9 August 2013); LILACS (1982 to 9 August 2013); and the Chinese Biomedical Literature Database (up to 10 November 2011), together with databases of ongoing trials. We contacted trial authors, authors of previous reviews and manufacturers in the field.
  
  
  METHODS
  We included all randomized controlled trials (RCTs), irrespective of blinding or language, that compared fibrinogen concentrate with placebo/other treatment or no treatment in bleeding patients, excluding neonates and patients with hereditary bleeding disorders.
  
  
  METHODS
  Three review authors independently abstracted data; we resolved any disagreements by discussion. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effects of fibrinogen concentrate in adults and children in terms of various clinical and physiological outcomes. We presented pooled estimates of the effects of intervention on dichotomous outcomes as risk ratios (RRs) and on continuous outcomes as mean differences, with 95% confidence intervals (CIs). We assessed the risk of bias through assessment of trial methodological components and the risk of random error through trial sequential analysis.
  
  
  RESULTS
  We included six RCTs with a total of 248 participants; none of the trials were determined to have overall low risk of bias. We found 12 ongoing trials, from which we were unable to retrieve any data. Only two trials provided data on mortality, and one was a zero event study; thus the meta-analysis showed no statistically significant effect on overall mortality (2.6% vs 9.5%, RR 0.28, 95% CI 0.03 to 2.33). Our analyses on blood transfusion data suggest a beneficial effect of fibrinogen concentrate in reducing the incidence of allogenic transfusions (RR 0.47, 95% CI 0.31 to 0.72) but show no effect on other predefined outcomes, including adverse events such as thrombotic episodes.
  
  
  CONCLUSIONS
  In the six available RCTs of elective surgery, fibrinogen concentrate appears to reduce transfusion requirements, but the included trials are of low quality with high risk of bias and are underpowered to detect mortality, benefit or harm. Furthermore, data on mortality are lacking, heterogeneity is high and acute or severe bleeding in a non-elective surgical setting remains unexplored. Currently, weak evidence supports the use of fibrinogen concentrate in bleeding patients, as tested here in primarily elective cardiac surgery. More research is urgently needed.
authors.affiliation: Department of Anaesthesiology, University of Copenhagen Herlev Hospital, Herlev, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Wikkelsø
authors.forename: Jens
authors.initials: J
authors.lastname: Lunde
authors.forename: Mathias
authors.initials: M
authors.lastname: Johansen
authors.forename: Jakob
authors.initials: J
authors.lastname: Stensballe
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.forename: Ann Merete
authors.initials: AM
authors.lastname: Møller
authors.forename: Arash
authors.initials: A
authors.lastname: Afshari
mesh_terms: D000328:Adult; D001803:Blood Transfusion / Q000706:statistics & numerical data; D006348:Cardiac Surgical Procedures; D002648:Child; D017558:Elective Surgical Procedures; D005340:Fibrinogen / Q000627:therapeutic use*; D006470:Hemorrhage / Q000401:mortality / Q000628:therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D005340:Fibrinogen