Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery

Abstract

It has been suggested that preoperative fibrinogen plasma concentration is independently associated to postoperative blood loss after cardiac surgery. Theoretically, prophylactic infusion of fibrinogen concentrate may thus reduce postoperative bleeding, but this has not previously been investigated. Twenty elective coronary artery bypass graft (CABG) patients with preoperative plasma fibrinogen levels <3.8 g/l were included in a prospective randomised pilot study. Patients were randomised to receive an infusion of 2 g fibrinogen concentrate (FIB group) or no infusion before surgery (control group). Primary endpoint was safety with clinical adverse events and graft occlusion assessed by multi-slice computed tomography. Predefined secondary endpoints were postoperative blood loss, blood transfusions, haemoglobin levels 24 hours (h) after surgery, and global haemostasis assessed with thromboelastometry, 2 and 24 hours after surgery. Infusion of 2 g fibrinogen concentrate increased plasma levels of fibrinogen by 0.6 +/- 0.2 g/l. There were no clinically detectable adverse events of fibrinogen infusion. Computed tomography revealed one subclinical vein graft occlusion in the FIB group. Fibrinogen concentrate infusion reduced postoperative blood loss by 32% (565 +/- 150 vs. 830 +/- 268 ml/12 h, p=0.010). Haemoglobin concentration was significantly higher 24 h after surgery in the FIB group (110 +/- 12 vs. 98 +/- 8 g/l, p=0.018). Prophylactic fibrinogen concentrate infusion did not influence global postoperative haemostasis as assessed by thromboelastometry. In conclusion, in this pilot study preoperative fibrinogen concentrate infusion reduced bleeding after CABG without evidence of postoperative hypercoagulability. Larger studies are necessary to ensure safety and confirm efficacy of prophylactic fibrinogen treatment in cardiac surgery.

Perioperative Administration of Fibrinogen is Associated with Increased Risk of Postoperative Thromboembolic Complications after Cardiac Surgery

“…All patients receiving additional coagulation factor concentrates were excluded as well as all patients without measured plasma fibrinogen level prior to fibrinogen infusion and after the number of adverse effects was reported and sufficient increase in plasma fibrinogen was seen after administration of an average 6.5 g; this was larger than the standard dose used in our patient group(2-3 g). One clinical randomized but not blinded trial has been done regarding fibrinogen infusion in cardiac surgery; the study included 20 CABG patients with preoperative fibrinogen <3.8g/L [10]. The primary outcomes were safety related to clinical adverse events and graft occlusion accessed by multi-slice computed tomography (CT).…”

“…It is converted in plasma by thrombin into a fibrin clot at the site of tissue damage in order to minimize blood loss and initiate tissue repair [9]. Administration of prophylactic fibrinogen has been shown to reduce postoperative bleeding after coronary artery bypass graft (CABG) [10] and previous studies have reported an inverse correlation between preoperative concentration of fibrinogen in plasma and the volume of postoperative bleeding after CABG [11][12][13][14][15]. This indicates that preoperative fibrinogen plasma concentration, even within the normal range, is a limiting factor for haemostasis after cardiac surgery.…”

“…Although the reported adverse effects of fibrinogen administration are few [17], without clinical significance [10,17] or blurred by the use of other medications influencing coagulation such as…”

How I use fibrinogen replacement therapy in acquired bleeding

“…78 Studies also suggest fibrinogen repletion will reduce bleeding and the need for allogeneic blood products. 79 A prospective study of fibrinogen concentrates in 61 patients with bleeding post-CPB noted fibrinogen reduced transfusions compared with placebo (2 U vs 13 U, respectively), and transfusion avoidance was achieved in half of the patients. 1 Other prospective and retrospective cardiac surgical studies, including high-risk ascending aortic replacement surgery, report that fibrinogen repletion with concentrates reduces postoperative bleeding and allogeneic blood product administration.…”

Coagulation Measurement and Optimisation in Cardiac Surgery

“…There is evidence that the low preoperative fibrinogen concentrations correlate with higher peri-operative blood loss in coronary artery bypass surgery (32,33). Pre-operative prophylactic fibrinogen infusion may be beneficial, although larger trials are required to determine safety and efficacy of this practice (34). Pre-operative hyperfibrinogenaemia is associated with higher all-cause mortality (35), possibly because raised fibrinogen levels are a marker of inflammation, reflecting the presence of a systemic disorder (eg sepsis, acute coronary syndrome).…”