Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial.
In their single-center, phase 2, prospective, randomized, double-blind, placebo-controlled clinical trial in 61 patients undergoing thoracoabdominal on-pump aortic replacement surgery, Rahe-Meyer and coworkers describe the effects of fibrinogen concentrate administered intraoperatively as targeted first-line hemostatic intervention on (1) the total number of units of allogeneic blood components (RBC, FFP, platelets) transfused (primary endpoint) as well as on (2) the number of units of each individual allogeneic blood component given and (3) the total avoidance of allogeneic transfusion (secondary endpoints). Fibrinogen dosing was based on thrombelastographic measurements. All patients received antifibrinolytic prophylaxis with tranexamic acid.
After cardiopulmonary bypass the impairment of fibrin formation has been identified a major cause of bleeding. A median dose of 8 g (6-9 g) of fibrinogen concentrate was administered in the fibrinogen group and led to a fibrinogen concentration of 260 ± 48 mg/dL at the time of suture (placebo-group 189 ± 34 mg/dL). During the 24-h period after start of study medication the median transfusion of allogeneic blood components was reduced by 85% in pts of the fibrinogen-group: median 2 units (0-8) vs. 13 units (8-21); fibrinogen vs. placebo group, p < 0.001). This effect was also present after differentiation between single allogeneic components: RBC reduction, 2 units; FFP reduction, 5 units; and platelet concentrate reduction, 2 units; fibrinogen vs. placebo group p < 0.05. A total avoidance of allogeneic transfusion was achieved in 45% of patients in the fibrinogen group and in 0% of patients in the placebo-group. None of the treatment-emergent adverse and serious adverse events was considered related to the study medication. In particular there was no increased thromboembolic risk in the fibrinogen group. In his editorial comment Nauder Faraday attests an impressive effect of fibrinogen-based hemostatic treatment but at the same time tempers enthusiasm until classic “intention-to-treat” protocols including larger numbers of patients confirm the promising data presented by Rahe-Meyer and coworkers. – Oliver Habler