Fibrinogen Concentrate as an Alternative to Cryoprecipitate in a Postcardiopulmonary Transfusion Algorithm in Infants Undergoing Cardiac Surgery: A Prospective Randomized Controlled Trial

Abstract

BACKGROUND: Infants undergoing cardiac surgery are at risk for bleeding and massive transfusion due to an immature coagulation system, complex surgeries, and cardiopulmonary bypass (CPB) effects. Hemodilution from CPB promotes an acquired hypofibrinogenemia that results in impaired fibrin formation, inadequate clot formation, and increased bleeding. In North America, the current standard of care to supplement fibrinogen is cryoprecipitate. An alternative option is the off-label use of fibrinogen concentrate (FC; RiaSTAP; CSL Behring, Marburg, Germany), a purified fibrinogen. Because perioperative allogenic transfusions are associated with increased morbidity and mortality, we sought to determine whether FC would be an acceptable alternative to cryoprecipitate in a post-CPB transfusion algorithm in infants undergoing open-heart surgery. METHODS: We randomized 60 infants (<12 months) undergoing nonemergent cardiac surgery with CPB at 2 tertiary care children’s hospitals to receive either cryoprecipitate or FC in a post-CPB transfusion algorithm. Infants underwent a stratified randomization based on institution and surgical complexity. The primary outcome was the difference in number of intraoperative allogenic blood product transfusions. Secondary outcomes included 24-hour chest tube output (CTO), mechanical ventilation time, adverse events (AEs), intensive care unit (ICU) length of stay (LOS), hospital LOS, postoperative thrombosis, and death within 30 days of surgery. The primary analysis followed the intent-to-treat (ITT) principle and was performed using linear regression adjusted for institution and complexity of surgery. A per-protocol (PP) analysis was also performed. RESULTS: Between June 2016 and January 2018, we enrolled 60 patients with complete data available for 25 patients who received cryoprecipitate and 29 patients who received FC. Patients in the cryoprecipitate group (median age: 4 months [2–6 months]) received 5.5 (4.0–7.0) allogeneic blood units in the ITT analysis and 6.0 units (5.0–7.0 units) in the PP analysis. Patients in the FC group (median age: 4 months [2–5]) received 4 units (3.0–5.0 units) in the ITT analysis and 4.0 units (3.0–5.0 units) in the PP analysis. In the adjusted ITT analysis, the FC group received 1.79 units (95% confidence interval [CI], 0.64–2.93; P = .003) less than the cryoprecipitate group. In the adjusted PP analysis, the FC group received 2.67 units (95% CI, 1.75–3.59; P < .001) less than the cryoprecipitate group. There were no significant differences in secondary outcomes or AEs. CONCLUSIONS: Our findings suggest that FC may be considered as an alternative to cryoprecipitate for the treatment of hypofibrinogenemia in infants with bleeding after CPB. Although we found no significant differences between secondary outcomes or AEs, further studies are needed to assess safety.

Prevention of postoperative bleeding after complex pediatric cardiac surgery by early administration of fibrinogen, prothrombin complex and platelets: a prospective observational study

“…Faraoni et al [12] demonstrated in a retrospective analysis that the post-CPB plasma fibrinogen concentration significantly impacts blood loss in children undergoing cardiac surgery. Downey et al [13] suggested that fibrinogen concentrate may be considered as an alternative to cryoprecipitate in infants with bleeding after CPB, but cryoprecipitate is not available in Germany. Mahovec et al demonstrated that measuring fibrinogen levels during the rewarming phase of CPB reduced cryoprecipitate transfusion [14].…”

Epidemiology of the Use of Hemostatic Agents in Children Supported by Extracorporeal Membrane Oxygenation: A Pediatric Health Information System Database Study

“…Significant hypofibrinogenemia/dysfibrinogenemia often occurs in patients on ECMO due to the binding of fibrinogen to the non-endothelial surface of the ECMO circuit and this has been associated with bleeding ( 4 ). Though less commonly used, fibrinogen concentrate has been shown to be associated with less allogeneic transfusions with no increased morbidity as compared to cryoprecipitate in children on cardiopulmonary bypass ( 18 ) and may be considered in children on ECMO as well.…”

Transfusion management for children supported by extracorporeal membrane oxygenation

“…While its use has not been studied in children or adults on ECMO, a recent trial comparing fibrinogen concentrate with cryoprecipitate in children on cardiopulmonary bypass demonstrated that those patients receiving fibrinogen concentrate received less allogenic blood products with no increased morbidity, compared to cryoprecipitate. 27 Many aspects of the storage and/or processing of each blood component may impact its effectiveness. Other than the age of storage of RBC transfusions, which did not show differences in tissue oxygenation as related to age, 28 no other aspects of processing, such as leukoreduction, irradiation, or pathogen reduction, have been evaluated.…”