Despite advances in trauma management over the past decade, haemorrhage in the setting of severe trauma remains a major cause of morbidity and mortality.
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Death related to haemorrhage is potentially preventable and represents a target for mortality reduction strategies. Traumatic haemorrhage is complicated by trauma-induced coagulopathy (TIC) — a complex clinical syndrome for which the pathophysiological mechanisms are not completely understood.
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Fibrinogen plays a critical role in maintaining effective haemostasis in traumatic haemorrhage and TIC. 8, 9, 10, 11
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Fibrinogen can be replaced with fresh frozen plasma (FFP), cryoprecipitate (Cryo) or fibrinogen concentrate (FC), which contain different concentrations of fibrinogen (2 g/L, 8–16 g/L and 20 g/L, respectively). The low concentration of fibrinogen in FFP and the large volumes required potentially make FFP unsuitable for dedicated fibrinogen replacement. 22, 23, 24
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Several key questions regarding fibrinogen replacement in traumatic haemorrhage remain unanswered, including:
- What tests, if any, should be used to guide fibrinogen replacement?
- What is the optimal product for fibrinogen replacement?
- What is the optimal dose of fibrinogen?
- What is the impact of early fibrinogen replacement on clinically important outcomes?
We conducted the Fibrinogen Early In Severe Trauma studY (FEISTY) randomised controlled pilot trial to assess the feasibility of early fibrinogen replacement using FC compared with Cryo in patients with traumatic haemorrhage and viscoelastic evidence of hypofibrinogenaemia. We aimed to determine whether fibrinogen replacement to reverse hypofibrinogenaemia could be achieved more rapidly using FC compared with Cryo and provide information for designing a more definitive trial.
Methods
FEISTY was an investigator-initiated, multicentre, randomised controlled, pilot trial comparing FC with Cryo for fibrinogen replacement in traumatic haemorrhage. It was conducted in four major trauma centres in Queensland, Australia, between December 2016 and September 2017. The trial was prospectively registered on ClinicalTrials.gov (NCT02745041). A full trial protocol has previously been published.
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Winearls J, Wullschleger M, Wake E, et al. Fibrinogen Early In Severe Trauma studY (FEISTY): study protocol for a randomised controlled trial. Trials 2017; 18: 241.
Eligibility criteria and randomisation
Adult trauma patients (aged ≥ 18 years) were eligible for enrolment if judged by treating clinicians to have clinically significant haemorrhage or potential for significant transfusion requirements with an assessment of blood consumption (ABC) score of ≥ 2.
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Patients were excluded if: they had injuries deemed incompatible with survival; they had received prior fibrinogen replacement (either FC or Cryo); greater than 6 hours had elapsed between injury and presentation; they had a known objection to blood product transfusion; they had a known coagulation disorder; they were known to be pregnant; or they were enrolled in a competing trial.
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Patients were randomly assigned to an intervention arm (1:1) using a block randomisation schedule produced by a statistician independent to the study, accommodating the possibility of unequal patient recruitment across the four sites. Secure, password-protected, web-based randomisation occurred on patient arrival to the trauma unit. Patients subsequently received protocol-directed FC or Cryo replacement. Allocation concealment was maintained through to the conclusion of the web-based randomisation process but, for practical and safety reasons, patients and their treating health care professionals were not blinded to the trial intervention. Trial integrity was supported by maintenance of blinding for outcome assessors and the trial statistician.