Abstract
We read with great interest the work by Swan et al, which evaluated hemostatic effects of Factor Eight Inhibitor Bypassing Activity (FEIBA) in pediatric patients undergoing cardiopulmonary bypass (CPB). 1 The authors concluded that post-CPB administration of FEIBA did not reduce the total volume of blood transfusion. However, the main endpoints they chose and the changes in practice over the course of patient enrollment warrant further discussion.
The primary endpoint, the total transfusion volume, incorporated platelets and cryoprecipitate were administered prior to FEIBA. The endpoint using pre-FEIBA transfusion volumes complicates the assessment of hemostatic activity of FEIBA due to potential interactions with either platelets or cryoprecipitate. Indeed, a previous pediatric CPB study demonstrated a possible interaction between fibrinogen and nonactivated prothrombin complex. 2 Propensity score matching was used to control for confounding factors before and during CPB, but post-CPB variation was not addressed nor adjusted by the authors. The residual confounding and interactions could have been alleviated by either adjusting for pre-FEIBA products in the analysis or by considering only post-FEIBA blood products. 3
The supplemental data showed that there were significant changes in hemostasis management during the study period. The introduction of Hepcon to assess heparin levels could have resulted in a distinct protamine dosing regimen and change in practices. The amount of protamine administered can indirectly affect transfused blood product volume by impacting activated clotting time in pediatric patients. 4 Similarly, the use of thromboelastography (TEG) after the year 2020 could have resulted in more aggressive cryoprecipitate use. 5 Although not statistically significant, the FEIBA group received higher cryoprecipitate volume compared with the other group. FEIBA, based on clinical judgment rather than using specific coagulation test parameters raises concerns about both internal and external validity of the findings.
There was a significant difference in the transfused red blood cell volumes between the FEIBA and control groups, indicating the blood-conserving effect of this off-label approach. According to approved indications, both prophylactic and on-demand usage of FEIBA have demonstrated hemostatic efficacy with few thromboembolic complications.6,7 The current study and others have shown that post-CPB use of FEIBA utilizing 1/5 to 1/10 of the hemophilia dose was not associated with any increase in thrombotic complications.6-8 However, both life-threatening 9 and less serious 10 intravascular thrombosis have been reported following the use of FEIBA in complex congenital heart surgeries. Therefore, a more restrictive use of FEIBA, based on thromboelastography or other laboratory criteria, is recommended over empirical use.
We commend the authors for contributing valuable data regarding FEIBA usage in their pediatric cardiac surgical practice. A low-dose FEIBA dosage is a promising hemostatic intervention for post-CPB coagulopathy. However, given the inherent limitations in the study design, further research is needed to establish a balanced risk–benefit profile for these highly vulnerable surgical populations.
