Fibrinolytic activity in infants undergoing cardiac surgery on cardiopulmonary bypass with routine tranexamic acid: A prospective cohort substudy within the FIBrinogen CONcentrate randomised control trial.

Background: Fibrinolytic activity contributes to bleeding after cardiopulmonary bypass (CPB).

Objective: Our objectives were, in a group of infants undergoing cardiac surgery with CPB: to document the extent of peri-operative fibrinolysis using rotational thromboelastometry (ROTEM) and standard biomarkers; to compare the agreement between these fibrinolytic measures; to assess whether fibrinolytic activity is associated with early postoperative mediastinal bleeding and assess whether supplementation with fibrinogen concentrate affected fibrinolysis.

Design: Prospective cohort, mechanistic substudy, nested within the FIBrinogen CONcentrate (FIBCON) randomised controlled trial.

Setting: Single centre, tertiary paediatric cardiac surgery and paediatric intensive care units.

Patients: Ninety infants (median age 6.3 months) undergoing cardiac surgery, who all received routine intra-operative tranexamic acid. The infants were randomised to receive either an individualised dose of fibrinogen concentrate (n = 60) or placebo (n = 30) during CPB.

Main Outcome Measures: We measured the ROTEM variable maximum clot lysis (ML), and fibrinolytic biomarkers including plasmin-antiplasmin (PAP) and tissue plasminogen activator antigen (tPA-Ag). Blood was sampled pre-CPB, on-CPB and post-CPB, and 4 h after PICU admission.

Results: tPA-Ag, PAP and ROTEM ML increased significantly after CPB despite the use of tranexamic acid. The two fibrinolytic biomarkers t-PA and PAP, correlated (P = 0.001) but neither correlated with ROTEM ML. Early postoperative blood loss was inversely associated with PAP levels. Each 100 μg l-1 rise in PAP was associated with a 7.9% reduction in mean blood loss. Fibrinogen concentrate supplementation as expected did not affect tPA-Ag but was temporally associated with an increase in PAP levels and a decrease in ROTEM fibrinolytic activity.

Conclusion: Fibrinolysis is activated after paediatric cardiac CPB surgery as indicated by increased tPA-Ag and ROTEM ML. The substantial increase in tPA-Ag post-PICU admission is probably accompanied by a similar rise of plasminogen activator inhibitor 1 (PAI-1) as part of the acute phase response to surgery, thereby limiting clinical fibrinolysis. Supplementation of fibrinogen concentrate was associated with increased PAP activity and less clinical bleeding, consistent with the known role for fibrinogen in being a substrate for plasmin.

Trial Registration: ISCTRN:50553029, Eudract:2013-003532-68.