Analysis of the structural and mechanical effects of procoagulant agents on neonatal fibrin networks following cardiopulmonary bypass.

Essentials The standard of care (SOC) for treating neonatal bleeding is transfusion of adult blood products. We compared neonatal clots formed with cryoprecipitate (SOC) to two procoagulant therapies. The current SOC resulted in clots with increased stiffness and decreased fibrinolytic properties. Procoagulant therapies may be a viable alternative to SOC treatment for neonatal bleeding. SUMMARY: Background Bleeding is a serious complication of neonates undergoing cardiopulmonary bypass (CPB) and associated with substantial morbidity and mortality. Bleeding is addressed through the transfusion of adult blood products, including platelets and cryoprecipitate. However, significant differences exist between neonatal and adult clotting components, specifically fibrinogen. Our recent ex vivo studies have shown that neonatal fibrinogen does not fully integrate with adult fibrinogen, leading to decreased susceptibility to fibrinolysis. These differences may contribute to ineffective clot formation and/or an increased risk of thrombosis. A need exists to identify more effective and safer methods to promote clotting in neonates. Objectives Procoagulant agents, such as prothrombin complex concentrates (PCCs) and recombinant activated factor VII (rFVIIa), are being used off-label to treat excessive bleeding in neonates after CPB. Because these agents stimulate endogenous fibrin formation, we hypothesize that their addition to post-CPB neonatal plasma will better recapitulate native clot properties than cryoprecipitate. Methods We analyze the structural, mechanical and degradation properties of fibrin matrices formed by neonatal plasma collected after CPB in the presence of an activated four-factor (F) PCC (FEIBA), rFVIIa, or cryoprecipitate using confocal microscopy, atomic force microscopy and a fluidics-based degradation assay. Results The ex vivo addition of FEIBA and rFVIIa to post-CPB neonatal plasma resulted in enhanced clot networks with differences in fibrin alignment, mechanics and degradation properties. Conclusions Our results suggest that these procoagulant agents could be used as an alternative to the transfusion of adult fibrinogen for the treatment of bleeding after CPB in neonates.