Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy.
In view of the low levels of fibrinogen in various clinical circumstances associated with haemorrhage, replacement of fibrinogen has become popular in recent years, despite the lack of solid clinical evidence regarding its efficacy.
In complex cardiac surgery, major blood loss may occur and the authors of this article hypothesised that administration of human fibrinogen concentrate in patients who present with major bleeding after bypass and proper surgical haemostasis might be beneficial. They performed a randomised controlled trial in 519 patients who underwent aortic surgery, of which 152 (29%) met the inclusion criteria (major blood loss) for administration of study medication (human fibrinogen concentrate, about 6 grams, titrated based on thrombelastography).
There was no significant effect of fibrinogen treatment on blood loss parameters. Surprisingly, patients receiving fibrinogen required more allogeneic blood products and were more often transfused. In conclusion, there was no beneficial effect of fibrinogen in this clinical setting. The authors note that the lack of effect of fibrinogen administration may have been due to the normal fibrinogen levels in their patients and the relatively low bleeding rates during their study.
This is an excellent clinical study with a solid methodology and a proper execution. The results are unexpected and once again underline that good clinical trials are important before embarking on interventions that may seem promising in preclinical settings or in initial uncontrolled observations. Based on these results, there is no place for routine administration of fibrinogen concentrate in patients undergoing complex cardiovascular surgery.
– Marcel Levi