Performance of functional fibrinogen thromboelastography in children undergoing congenital heart surgery

Background: Functional Fibrinogen assay of the Thromboelastography (FFTEG), a whole blood viscoelastic hemostatic assay, has been used to estimate fibrinogen levels in adult patients undergoing major surgery but its performance in pediatric patients undergoing cardiac surgery requires evaluation. In this study, we evaluate the correlation between FFTEG parameters and standard laboratory tests for fibrinogen and platelet counts before and after cardiopulmonary bypass in children undergoing repair for congenital heart disease.

Methods: In this prospective observational study, whole blood samples were obtained from children less than 5 years of age undergoing congenital heart surgery with cardiopulmonary bypass before surgical incision and immediately after administration of protamine. Blood samples were analyzed for Thromboelastography, Functional Fibrinogen level measured by FFTEG (FLEV), complete blood counts with platelet count and plasma fibrinogen assay (LFib, Clauss). The primary outcome of this study was to assess the correlation between FFTEG parameters, LFib and platelet counts in neonates, infants, and small children less than 5 years old. Additionally, we studied if postbypass FFTEG parameters could predict critical thresholds of hypofibrinogenemia LFib ≤200 mg·dl^-1 .

Results: One hundred and five children (22 neonates, 51 infants, and 32 small children) were included in the final analysis. FLEV estimated higher fibrinogen levels than LFib in all patients. Before bypass, FLEV was on average 133 mg·dl^-1 higher than LFib (95% confidence interval, CI, 116-150, P < 0.001) for all the patients; after bypass, FLEV was 48 mg·dl^-1 (95% CI: 37-59, P < 0.001) higher than LFib for all the patients. Linear correlation coefficients between FLEV and LFib in all patients were R = 0.41 (95% CI: 0.24-0.56, P < 0.001) before bypass and increased to R = 0.63 (95% CI: 0.51-0.74, P < 0.001) after bypass. Bland Altman analysis performed on postbypass values of FLEV and LFib showed a positive bias of FLEV in estimation of LFib. The magnitude and the variability of the bias for all the patients group was decreased with lower mean of the difference of FLEV and LFib when the average values of FLEV and LFib were <200 mg·dl^-1 . Low linear correlations were noticed between maximal amplitude of platelet contribution to FFTEG and platelet counts both before and after bypass. For predicting the clinical thresholds of postbypass hypofibrinogenemia at plasma fibrinogen levels ≤200 mg·dl^-1 , FLEV and maximal amplitude of the fibrinogen clot generated area under receiver operative curves at 0.90 (95% CI = 0.76-1.0) in neonates, 0.6 (95% CI- 0.42-0.78) in infants, and 0.97 (95% CI = 0.91-1.0) in small children. Based on the receiver operative curves, values of postbypass hypofibrinogenemia with LFib ≤200 g·dl^-1 corresponded to cutoffs of FLEV_POST ≤245 mg·dl^-1 and maximal amplitude of the fibrinogen clot ≤13.4 mm.

Conclusion: In pediatric patients undergoing cardiac surgery, FLEV derived from Functional Fibrinogen correlated linearly with plasma fibrinogen levels (Clauss) both before and after CPB. FLEV estimation of plasma fibrinogen was improved after CPB in neonates, infants, and small children. After CPB, FFTEG can be used to predict laboratory diagnosis of critical hypofibrinogenemia (≤200 mg·dl^-1 ) during pediatric cardiac surgery. Further studies are required to assess the impact of predictability of FFTEG on component transfusion during pediatric cardiac surgery.