Fibrinogen concentrate noninferior to cryoprecipitate after cardiac surgery in patients with excessive bleeding and hypofibrinogenemia

1. The use of fibrinogen concentrate for fibrinogen replacement, post cardiac surgery, is noninferior to cryoprecipitate.

Evidence Rating Level: 1 (Excellent)

Study Rundown: A common postoperative complication with cardiac surgery is excessive bleeding which consequently requires blood component transfusion.  The guidelines for the management of cardiac surgery-associated bleeding presenting with acquired hypofibrinogenemia recommend use of either cryoprecipitate or fibrinogen concentrate as treatment options.  Despite knowing that cryoprecipitate is a non-purified product, has a limited shelf life, and is more difficult to store and administer when compared to fibrinogen concentrate, it remains the treatment of choice in much of North America.  This study evaluated the first 24 hours after cardiopulmonary bypass, to analyze the mean number of blood components transfused.  The results demonstrated a lower mean value for the allopathic transfusions of the group receiving the fibrinogen concentrate compared to the cryoprecipitate.

This study successfully randomized a large sample size into the study treatment groups while assuring the baseline variables remained balanced.  The study was limited by a lack of blinding of the clinicians to the treatment assignment, however, this did not lead to any differences with the timing of transfusions compared to the administering of the treatment.  Furthermore, the outcome collection part of the study was completed by blinding the outcome assessors and the patients to treatment allocation.  The adverse events and transfusion data was reviewed independently by monitors which strengthens the findings. Lastly, the study results are not generalizable to all patients receiving fibrinogen replacement therapy, given the study inclusion criteria recruiting strictly patients with excessive bleeding post cardiac surgery.

Click here to read the study in JAMA

Relevant reading: Hemostatic effects of fibrinogen concentrate compared with cryoprecipitate in children after cardiac surgery

In-Depth [randomized controlled trial]: This randomized control trial enrolled a total of 827 participants across 11 Canadian hospitals from February 2017 to November 2018.  Within 24 hours of patients presenting with excessive bleeding and acquired hypofibrinogenemia post cardiopulmonary bypass, eligible participants were randomized to be in either the cryoprecipitate group (n=412) or the fibrinogen group (n=415) depending on the ordered dose and treatment.  Patients were classified using the Clauss method (fibrinogen plasma level <2.0g/L) or FIBTEM (fibrin-based thromboelastometry test extrinsically activated with tissue factor and containing the platelet inhibitor cytochalasin D) – derived clot at 10 minutes <100mm by thromboelastometry.  The study exclusion criteria consisted of already having received fibrinogen replacement within 24 hours before surgery, allergies to the study treatments, refusal of receiving blood components for religious or other reasons, plasma fibrinogen level > 3.0g/L within 30 minutes of treatment order and/or known pregnancy. Mean 24-hour post-bypass allogeneic transfusions indicated 16.3 units in the fibrinogen concentrate group (95% CI, 14.9 to 17.8) and 17.0 units in the cryoprecipitate group (95%CI, 15.6 to 18.6)(ratio, 0.96 [1-sided 97.5%CI, ∞− to 1.09; P < .001 for noninferiority] [2-sided 95%CI, 0.84 to 1.09; P = .50 for superiority]). Only 61 patients from the recruited patients, reported a thromboembolic event post treatment, of which 35 belonged to the cryoprecipitate group and 26 in the fibrinogen concentrate group. The findings suggest that fibrinogen concentrate group is noninferior to the cryoprecipitate group after cardiac surgery in patients with excessive bleeding and hypofibrinogenemia.

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