Pro-Con Debate

Fibrinogen Concentrate or Cryoprecipitate for Treatment of Acquired Hypofibrinogenemia in Cardiac Surgical Patients

Nadia B. Hensley, MD; Michael A. Mazzeffi, MD, MPH, MSc, FASA

Disclosures

Anesth Analg. 2021;133(1):19-28. 

In This Article

Fibrinogen Concentrate Advantage: Evidence of Safety and Efficacy in Cardiac Surgical Patients

There have been several randomized controlled trials of fibrinogen concentrate in cardiac surgical patients (Table 2).[24,35–42] One of the first trials conducted by Karlsson et al[35] randomized elective coronary artery bypass grafting (CABG) patients who had a preoperative plasma fibrinogen concentration of ≤380 mg/L. Randomized patients received an infusion of 2 g fibrinogen concentrate (n = 10) or no infusion (n = 10) immediately before surgery.[35] Primary end points were clinically detectable adverse events and early graft occlusion by cardiac computed tomography (CT). There was 1 vein graft occlusion in the fibrinogen concentrate group, and no vein graft occlusions in the control group. All left internal mammary grafts were patent in both groups.

Rahe-Meyer et al[36] conducted another small randomized trial in patients undergoing elective aortic valve and ascending aortic replacement surgery. In 1 group (n = 5), patients were treated with a transfusion algorithm based on the platelet count at cross-clamp removal and bleeding (defined by >60 g of blood weighed on surgical swabs), and in the other group (n = 10), patients were given fibrinogen concentrate before being transfused according to an algorithm. For the primary end point, the use of allogeneic blood products, the fibrinogen concentrate group was transfused fewer RBC units (0.5 ± 1.1 vs 2.4 ± 1.1), fewer FFP units (0.2 ± 0.6 vs 4.5 ± 2.1), and fewer platelet units (0.0 ± 0.0 vs 1.6 ± 1.7).[36]

Ranucci et al[39] enrolled 116 cardiac surgical patients and randomized them to receive either fibrinogen concentrate or placebo after protamine was given. Fibrinogen concentrate was given based on the rotational thromboelastometry (ROTEM; TEM International, Munich, Germany) parameters.[39] Fifteen minutes after fibrinogen concentrate was given, patients could receive prothrombin complex concentrate if ROTEM parameters remained abnormal. The authors found that 67.2% of patients in the treatment arm avoided any allogeneic transfusion (primary outcome) compared to 44.8% in the control group (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.19–0.84).

The largest randomized multicenter clinical trial of fibrinogen concentrate, the FIBrinogen REplenishment in Surgery (FIBRES) study, enrolled 725 patients at 11 centers in Canada (Table 2).[24] This study included adult patients who had significant bleeding related to acquired hypofibrinogenemia after CPB, defined as fibrinogen <200 mg/dL by the Clauss method or the fibrin-based thromboelastometry test extrinsically activated with tissue factor and containing the platelet inhibitor cytochalasin D (FIBTEM) amplitude <10 mm at 10 minutes. Randomized patients received 4 g of fibrinogen concentrate or 10 units of cryoprecipitate. Mean 24-hour post-CPB cumulative allogeneic transfusions were 16.3 units (95% CI, 14.9–17.8) in the fibrinogen concentrate group and 17.0 units (95% CI, 15.6–18.6) in the cryoprecipitate group. These findings met the prespecified criteria for noninferiority. Noninferiority was also met for the secondary outcomes, including 24-hour and cumulative 7-day blood component transfusion and cumulative transfusion measured from product administration to 24 hours after CPB. The trial was stopped prematurely due to noninferiority being satisfied.[24]

processing....