OA2-AM24-MN-23 - Phase IV Trial Of Pathogen-reduced Cryoprecipitate vs. Cryoprecipitated AHF to Lower Operative Transfusions (TOP-CLOT) in Cardiac Surgery

Low perioperative levels of fibrinogen are associated with severity of hemorrhage and increased transfusion of blood components in cardiac surgery. The ability to supplement fibrinogen during hemorrhage is often delayed >45 minutes because CryoAHF (Cryo) is stored frozen, due to a short post-thaw shelf life. Pathogen Reduced Cryoprecipitated Fibrinogen Complex, Intercept Fibrinogen Complex (IFC) can be kept thawed at room temperature for up to 5 days, and thus immediately available for hemorrhaging patients. This single center, prospective, cluster randomized clinical trial compared IFC to Cryo in bleeding cardiac surgery patients with hypofibrinogenemia with the hypothesis that the earlier availability of IFC might lead to earlier hemostasis and reduced transfusions overall.

Study

Design/Methods:

During the trial, all hospital cryoprecipitate orders were cluster randomized by month to be fulfilled with either IFC or Cryo. Bleeding cardiac surgery patients were enrolled if either component was transfused intraoperatively for acquired hypofibrinogenemia (indication FIBTEM A10 ≤ 10 mm).  The primary outcome was the total number of allogeneic blood products (red blood cells, plasma, and platelets) transfused within 30 days of surgery. Fisher’s exact test, Pearson’s Chi-squared test, and Wilcoxon rank sum test were used to evaluate baseline characteristics and outcomes between the groups.  Multivariable linear and logistic regression models were used to assess the association of IFC use with each outcome, adjusting for the effects of patient baseline characteristics.

Results/Findings:

The trial enrolled 173 subjects: 86 in the IFC and 87 in the Cryo arms. Median FIBTEM A10 prior to first cryo transfusion was 7 mm and all patients were bleeding. There were no significant differences in baseline patient characteristics between groups. There were no significant differences in the primary outcome or any of the secondary clinical outcomes (Table 1).  Time from order to issue and order to start of transfusion, were 19 and 11 minutes shorter (p< 0.001), respectively, with IFC. Fibrinogen levels measured immediately after surgery showed no difference, indicating that both performed similarly in terms of fibrinogen replacement.  Transfusion related adverse events did not differ between the products.

Conclusions:

This is the first trial of IFC in humans and demonstrates its safety for treating acute bleeding in cardiac surgery, with earlier availability of IFC in the OR.  Cryo and IFC showed similar post transfusion fibrinogen levels and blood component utilization.   Pre-ordering cryoprecipitate before active bleeding was seen in both groups and thus IFC was not transfused earlier during surgery.  This hindered our ability to test our hypothesis.  Having IFC available at the bedside rather than in the blood bank may demonstrate further benefit in reducing blood transfusion.