Effects of Fibrinogen Concentrate as First-line Therapy during Major Aortic Replacement Surgery

Abstract

Background: Fibrinogen is suggested to play an important role in managing major bleeding. However, clinical evidence regarding the effect of fibrinogen concentrate (derived from human plasma) on transfusion is limited. The authors assessed whether fibrinogen concentrate can reduce blood transfusion when given as intraoperative, targeted, first-line hemostatic therapy in bleeding patients undergoing aortic replacement surgery. Methods: In this single-center, prospective, placebocontrolled, double-blind study, patients aged 18 yr or older undergoing elective thoracic or thoracoabdominal aortic replacement surgery involving cardiopulmonary bypass were randomized to fibrinogen concentrate or placebo, administered intraoperatively. Study medication was given if patients had clinically relevant coagulopathic bleeding immediately after removal from cardiopulmonary bypass and completion of surgical hemostasis. Dosing was individualized using the fibrin-based thromboelastometry test. If bleeding continued, a standardized transfusion protocol was followed. Results: Twenty-nine patients in the fibrinogen concentrate group and 32 patients in the placebo group were eligible for the efficacy analysis. During the first 24 h after the administration of study medication, patients in the fibrinogen concentrate group received fewer allogeneic blood components than did patients in the placebo group (median, 2 vs. 13 U; P < 0.001; primary endpoint). Total avoidance of transfusion was achieved in 13 (45%) of 29 patients in the fibrinogen concentrate group, whereas 32 (100%) of 32 patients in the placebo group received transfusion (P < 0.001). There was no observed safety concern with using fibrinogen concentrate during aortic surgery.

Plasma fibrinogen concentration is correlated with postoperative blood loss in children undergoing cardiac surgery

“…Fibrinogen concentrate was recently used as a first-line therapy in algorithm-based management of the bleeding patient. 12 In that first prospective, randomised study performed in patients undergoing aortic surgery, fibrinogen concentrate significantly reduced the transfusion of allogeneic blood products. 24 However, further well designed, prospective, randomised controlled trials assessing the efficacy and the safety of fibrinogen concentrate in cardiovascular surgery, in particular in the paediatric population, are required before such therapy could be recommended in routine practice.…”

“…7,8 Fibrinogen concentrate has been used in Europe for many years in cases of congenital fibrinogen deficiency. 9 However, a growing literature in adults has demonstrated the efficacy of fibrinogen concentrate in patients with acquired hypofibrinogenaemia associated with trauma, 10 cardiac surgery 11,12 or massive bleeding. 13 This relatively new approach for fibrinogen replacement is based on (patho)physiological considerations.…”

Comparison of functional fibrinogen (FF/CFF) and FIBTEM in surgical patients – a retrospective study

“…While low fibrinogen levels have been associated with increased surgery-and traumarelated bleeding [5][6][7][8][9], persistently high fibrinogen levels are associated with an increased risk of acute coronary syndrome and ischemic stroke [10,11]. Targeting a fairly high FIBTEM maximum clot firmness (MCF) of 22 mm, first-line hemostatic therapy with fibrinogen reduced transfusion requirements after major thoracic and thoracoabdominal surgery as compared to placebo in an experimental clinical study setting [12]. Nevertheless, the target MCF levels for less invasive cardiac surgery and for trauma patients have not yet been clearly defined.…”

Adjunct agents for bleeding

“…The role of fibrinogen supplementation for the treatment or prevention of bleeding in critical patients has been investigated [30 && ,31 && ]. For instance, in the frame of a placebo-controlled randomized trial including 61 patients undergoing aortic replacement surgery on cardiopulmonary bypass, the transfusion of allogeneic blood was dramatically reduced in patients receiving fibrinogen concentrate (median two versus 13 units, P < 0.001) [32]. Most importantly, a Cochrane review [33 & ] that was published in the past year on the use of fibrinogen supplementation in bleeding patients, including six randomized controlled trials with a total of 248 participants, found a beneficial effect of fibrinogen in reducing the incidence of allogeneic transfusions (RR 0.47, 95% CI 0.31-0.72).…”