In this unblinded randomised controlled trial that enrolled 43 adult trauma patients at two major UK civilian trauma centres, Curry et al. investigated whether it is feasible to administer cryoprecipitate (two pools, corresponding to ~4 g fibrinogen) to haemorrhaging trauma patients within 90 minutes of hospital admission and whether such early cryoprecipitate therapy influences the fibrinogen level and clinical outcome. The authors report that 85% (95% CI 69-100%) of patients in the intervention group received cryoprecipitate within 90 minutes, i.e. faster than in patients receiving standard major haemorrhage therapy (median time 60 min (IQR: 57-76) vs. 108 min (IQR: 67-147); P = 0.002). Fibrinogen concentrations were higher in the intervention group and were above 1.8 g/L at all time-points during active haemorrhage. All-cause mortality at 28 days did not differ between patient receiving early cryoprecipitate and standard therapy (10.0% vs. 28.6%; P = 0.14). The authors conclude that early fibrinogen supplementation using cryoprecipitate is feasible in trauma patients, but that there is a need for a definitive randomised controlled trial.

Low fibrinogen in haemorrhaging trauma patients is associated with poor outcome and low fibrinogen administration during resuscitation (via dilution by crystalloids/colloids or via unbalanced blood products, evaluated by the ratio of plasma, cryoprecipitate or fibrinogen concentrate to red blood cells) is associated with excess mortality, indicating that it may be beneficial to increase fibrinogen levels in haemorrhaging trauma patients. However, fibrinogen can be administered from different sources (plasma, cryoprecipitate or fibrinogen concentrate), each having a specific dose and feasibility-risk-benefit profile.

This pilot study by Curry et al. evaluating the feasibility and influence on fibrinogen levels of early cryoprecipitate administration is an important study for the planning of future randomised controlled trials evaluating the effect on outcome of early fibrinogen administration. Such randomised controlled trials should optimally compare early administration of cryoprecipitate with early administration of fibrinogen concentrate as compared to control in haemorrhaging trauma patients resuscitated with balanced ratios of plasma, platelets and red blood cells. Furthermore, in order to personalise early resuscitation, such randomised controlled trials should evaluate the application of viscoelastic haemostatic assays (TEG®, ROTEM®) to allow early identification of patients with low fibrinogen levels and to guide timing and dosing of the administered fibrinogen source.

– Sisse Rye Ostrowski