Bleeding is an important and potentially preventable adverse event associated with surgery. Prevention, or treatment, of bleeding must be balanced against the risk of arterial or venous thrombotic events. Fibrin, which is formed from fibrinogen, is a key part of blood clot formation. In situations where a patient’s fibrinogen concentration is low, fibrinogen concentrate (or another source of fibrinogen such as cryoprecipitate) is often administered. However it is less clear whether fibrinogen concentrate is effective and safe for patients with a normal baseline fibrinogen level.
An alternate, or adjuvant approach, is the use of anti-fibrinolytic agents (which prevent fibrin from being broken down) such as tranexamic acid and epsilon aminocaproic acid. These drugs are increasingly used to prevent peri-operative blood loss and do not appear to be associated with significant adverse events.
A systematic review and meta-analysis published in 2013 on fibrinogen concentrate in surgical patients found no difference in mortality but found a significant reduction in the incidence of red cell transfusion (Wikkelsø et al. Cochrane Database Syst Rev 2013;8:CD008864).
The authors set out to compare efficacy and safety of fibrinogen concentrate in surgical patients in a systematic review and meta-analysis. Randomised controlled trials including adult or paediatric surgery were included. Trials were included if they compared fibrinogen concentrate to placebo or another haemostatic therapy (fresh frozen plasma, platelets, cryoprecipitate or coagulation factor concentrates). The only exclusion was congenital (inherited) fibrinogen deficiency.
The primary outcome was all-cause mortality. Secondary outcomes were blood loss; proportion of patients who received a red cell transfusion; number of red cell units used; surgical revisions for bleeding; and thrombotic complications.
The authors identified 14 randomised controlled trials with 1035 patients. The majority of trials were in the setting of cardiac surgery. There was a high level of variation in the comparators that were used, the trigger for infusion of fibrinogen concentrate; prophylactic or therapeutic use; the timing of administration; and the dose of fibrinogen concentrate. The authors reported that half of the included studies were at high or moderate risk of bias.
The risk of all-cause mortality was significantly lower in the group treated with fibrinogen concentrate. The event rate for mortality was very low with the majority of trials having no deaths in either arm. The meta-analysis included an unpublished paper and exclusion of this paper form the meta-analysis resulted in a non-significant difference in mortality (Mengoli et al. J Cardiothorac Vasc Anesth 2017;31:e33-5).
Blood loss; number of red cell units transfused; and proportion of patients who received a red cell transfusion were significantly lower for those treated with fibrinogen concentrate. No difference was found in the risk of surgical revisions for bleeding or thrombotic complications.