Complement activation by the artificial surface of cardiopulmonary bypass is a persistent clinical problem

Activation of the alternative complement pathway by artificial extracorporeal surfaces is relevant to several clinical applications such as cardiac surgery with cardiopulmonary bypass (CPB), thoracic organ transplantation and hemodialysis. In the pediatric cardiac surgery population, complement mediators have been associated with systemic inflammation, post-operative morbidity and delayed recovery. Small children require CPB circuit prepared with allogeneic blood products and these sanguineous primes have substantially higher concentrations of biologically active anaphylatoxins C3a and C5a relative to the patient’s baseline circulation. Sequential samples were collected during forty-five ex-vivo sanguineous prime preparations of CPB circuits coated with phosphorylcholine, as a biocompatibility technology, to characterize complement activation in this context. We observed and quantified evidence of alternative and terminal complement pathway activation indicated by dynamic concentration increases of C3a, C3b, C5a and terminal complement complex. Circuit exposure time was a predictor of only C3a concentration in multivariable generalized linear mixed-effects models. Despite modern biocompatibility technology, there is significant alternative complement activation during ex-vivo sanguineous CPB prime preparation. Patient exposure to this activated mediator burden during CPB could promote systemic endothelial inflammation with negative end-organ and post-operative clinical impacts. Further research is required to evaluate and inhibit complement responses to artificial surfaces broadly used for clinical care.