title: Early cryoprecipitate for major haemorrhage in trauma: a randomised controlled feasibility trial.
abstract: BACKGROUND
  Low fibrinogen (Fg) concentrations in trauma haemorrhage are associated with poorer outcomes. Cryoprecipitate is the standard source for Fg administration in the UK and USA and is often given in the later stages of transfusion therapy. It is not known whether early cryoprecipitate therapy improves clinical outcomes. The primary aim of this feasibility study was to determine whether it was possible to administer cryoprecipitate, within 90 min of admission to hospital. Secondary aims were to evaluate laboratory measures of Fg and clinical outcomes including thrombotic events, organ failure, length of hospital stay and mortality.
  
  
  METHODS
  This was an unblinded RCT, conducted at two civilian UK major trauma centres of adult trauma patients (age ≥16 yrs), with active bleeding and requiring activation of the major haemorrhage protocol. Participants were randomised to standard major haemorrhage therapy (STANDARD) (n=22), or to standard haemorrhage therapy plus two early pools of cryoprecipitate (CRYO) (n=21).
  
  
  RESULTS
  85% (95% CI: 69-100%) CRYO participants received cryoprecipitate within 90 min, median time 60 min (IQR: 57-76) compared with 108 min (67-147), CRYO and STANDARD arms respectively (P=0.002). Fg concentrations were higher in the CRYO arm and were maintained above 1.8 g litre(-1) at all time-points during active haemorrhage. All-cause mortality at 28 days was not significantly different (P=0.14).
  
  
  CONCLUSIONS
  Early Fg supplementation using cryoprecipitate is feasible in trauma patients. This study supports the need for a definitive RCT to determine the effect of early Fg supplementation on mortality and other clinical outcomes.
  ISRCTN55509212.
authors.affiliation: Department of Haematology, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Oxford, UK nicola.curry@ouh.nhs.uk.
authors.forename: N
authors.initials: N
authors.lastname: Curry
authors.affiliation: Centre for Trauma Sciences, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Rourke
authors.affiliation: Centre for Trauma Sciences, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Davenport
authors.affiliation: Department of Haematology, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Beer
authors.affiliation: NHS Blood and Transplant Clinical Trials Unit, NHS Blood & Transplant, Cambridge and Bristol, UK.
authors.forename: L
authors.initials: L
authors.lastname: Pankhurst
authors.affiliation: NHS Blood and Transplant Clinical Trials Unit, NHS Blood & Transplant, Cambridge and Bristol, UK.
authors.forename: A
authors.initials: A
authors.lastname: Deary
authors.affiliation: NHS Blood and Transplant Clinical Trials Unit, NHS Blood & Transplant, Cambridge and Bristol, UK.
authors.forename: H
authors.initials: H
authors.lastname: Thomas
authors.affiliation: NHS Blood and Transplant Clinical Trials Unit, NHS Blood & Transplant, Cambridge and Bristol, UK.
authors.forename: C
authors.initials: C
authors.lastname: Llewelyn
authors.affiliation: Department of Haematology, Barts Health NHS Trust, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Green
authors.affiliation: NHS Blood and Transplant, Birmingham, UK.
authors.forename: H
authors.initials: H
authors.lastname: Doughty
authors.affiliation: Plymouth Hospitals NHS Trust, Plymouth, UK The Academic Department of Military Anaesthesia and Critical Care, Royal Centre for Defence Medicine, Birmingham, UK.
authors.forename: G
authors.initials: G
authors.lastname: Nordmann
authors.affiliation: Centre for Trauma Sciences, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Brohi
authors.affiliation: Department of Haematology, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Stanworth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001803:Blood Transfusion / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005340:Fibrinogen / Q000627:therapeutic use*; D006470:Hemorrhage / Q000150:complications* / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014193:Trauma Centers; D006113:United Kingdom; D014947:Wounds and Injuries / Q000150:complications*; D055815:Young Adult
chemical_list: D005340:Fibrinogen
keywords: cryoprecipitate; fibrinogen; haemorrhagic shock; multiple trauma