Is it feasible to trial giving fibrinogen concentrate in major trauma?

Start by doing what’s necessary; then do what’s possible; and suddenly you are doing the impossible. – Francis of Assisi

Fibrinogen in the initial Resuscitation of Severe Trauma (FiiRST): a randomized feasibility trial. B. Nascimento et al. BJA Dec 2016. doi: 10.1093/bja/aew343

This is a Canadian study looking at the feasibility of administering Fibrinogen Concentrate (FgC) within 1 hour of hospital admission of severe trauma patients.

Acute traumatic coagulopathy with hypofibrinogenaemia is a leading cause of early mortality in trauma patients. Cryoprecipitate, as a source of fibrinogen, is the current standard in many countries, but limited evidence exists supporting the use of Fibrinogen Concentrate in this scenario. The authors set out to evaluate the feasibility of early infusion, its effects on the plasma concentration of Fg, as well as complications of early infusion.

This was a Single-Centre Double-Blind Randomized Control Trial that took place over a 1 year period. Adult patients with severe trauma who were identified to be at risk of significant haemorrhage, and met the correct criteria, were randomized by the hospital Blood Bank to either the placebo arm (Normal Saline) or the FgC arm. Both interventions were administered rapidly as a total volume of 300ml in a concealed bag, after which blood products were given as per the local major haemorrhage protocol. A target of 30mins from request to start of infusion was set.

Fifty patients were randomized and five were excluded post-randomization due to an error in initial selection. There was an observed difference in median age, but no significant differences in any of the baseline characteristics between the two groups, including injury severity, time to hospital and baseline clotting screen, were found. There were also no differences in co-interventions received, which ranged from Tranexamic Acid administration to laparotomy, and also no difference in the number of units of blood products transfused.

95% of participants received an intervention within one hour. The median time was 50 mins and at the lower 95% confidence interval, >85% of participants received fibrinogen or placebo within the hour. This demonstrates significant evidence of feasibility. Plasma fibrinogen concentration increased by approximately 1g/l in the FgC group, and remained higher than the placebo group until 12 hours post-hospitalization, after which there was no difference in measured concentration between the groups. There was also no difference in mortality or thrombo-embolic complications.

This was a well-designed trial, in-part funded by the makers of FgC, that met its primary objective.  The effect of FgC on Fg levels in early trauma was also demonstrated, but as the trial was not powered to detect differences in complications or patient outcomes so conclusions can be drawn in this respect. The impact of the increased work on the Blood Bank was not revealed and it would be interesting to see if the lab could meet the set target with a four-fold increase in work-load (the institution receives approximately 200 trauma patients with significant bleeding annually). This study is, however, very unlikely to change practice with the cost of FgC being six times that of 2 units of Cryoprecipitate, which is totally unrealistic in the current NHS climate!

Summary by Dr Dina Abdel-Gadir

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