title: Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.
abstract: BACKGROUND
  In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH.
  
  
  METHODS
  In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death.
  
  
  RESULTS
  Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected.
  
  
  CONCLUSIONS
  We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia.
  
  
  BACKGROUND
  ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev DK-2730, Denmark wikkelso@gmail.com.
authors.forename: A J
authors.initials: AJ
authors.lastname: Wikkelsø
authors.affiliation: Department of Obstetrics and Gynaecology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev DK-2730, Denmark.
authors.forename: H M
authors.initials: HM
authors.lastname: Edwards
authors.affiliation: Department of Anaesthesia, Mother and Child Section, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, KBH Ø DK-2100, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Afshari
authors.affiliation: Department of Anaesthesia, Centre of Head and Orthopaedics, and Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, KBH Ø DK-2100, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Stensballe
authors.affiliation: Department of Obstetrics, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, KBH Ø DK-2100, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Langhoff-Roos
authors.affiliation: Department of Anaesthesia, Mother and Child Section, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, KBH Ø DK-2100, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Albrechtsen
authors.affiliation: Department of Anaesthesia, Mother and Child Section, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, KBH Ø DK-2100, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Ekelund
authors.affiliation: Department of Anaesthesia, Mother and Child Section, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, KBH Ø DK-2100, Denmark.
authors.forename: G
authors.initials: G
authors.lastname: Hanke
authors.affiliation: Department of Anaesthesia, Mother and Child Section, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, KBH Ø DK-2100, Denmark.
authors.forename: E L
authors.initials: EL
authors.lastname: Secher
authors.affiliation: Department of Obstetrics, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, KBH Ø DK-2100, Denmark.
authors.forename: H F
authors.initials: HF
authors.lastname: Sharif
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, Hvidovre Hospital, University of Copenhagen, Kettegård Allé 30, DK-2650, Denmark.
authors.forename: L M
authors.initials: LM
authors.lastname: Pedersen
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, Hvidovre Hospital, University of Copenhagen, Kettegård Allé 30, DK-2650, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Troelstrup
authors.affiliation: Department of Obstetrics and Gynaecology, Hvidovre Hospital, University of Copenhagen, Kettegård Allé 30, DK-2650, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Lauenborg
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev DK-2730, Denmark.
authors.forename: A U
authors.initials: AU
authors.lastname: Mitchell
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev DK-2730, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Fuhrmann
authors.affiliation: Department of Obstetrics and Gynaecology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev DK-2730, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Svare
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, Hillerød Hospital, University of Copenhagen, Dyrehavevej 29, Hillerød DK-3400, Denmark.
authors.forename: M G
authors.initials: MG
authors.lastname: Madsen
authors.affiliation: Department of Obstetrics and Gynaecology, Hillerød Hospital, University of Copenhagen, Dyrehavevej 29, Hillerød DK-3400, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Bødker
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev DK-2730, Denmark.
authors.forename: A M
authors.initials: AM
authors.lastname: Møller
mesh_terms: D004311:Double-Blind Method; D017707:Erythrocyte Transfusion; D005260:Female; D005340:Fibrinogen / Q000009:adverse effects / Q000627:therapeutic use*; D006487:Hemostasis; D006801:Humans; D006473:Postpartum Hemorrhage / Q000097:blood / Q000188:drug therapy*; D011247:Pregnancy; D016896:Treatment Outcome
chemical_list: D005340:Fibrinogen
keywords: blood coagulation; erythrocyte transfusion; fibrinogen; postpartum haemorrhage