Investigating Thrombosis in Mechanical Circulatory Support Devices

Abstract

Mechanical circulatory support devices (MCS), such as extracorporeal membrane oxygenation (ECMO), assist perfusion in critically ill cardiorespiratory patients. Yet, thrombosis in such devices risks adverse events, including circuit occlusion and failure, and patient embolism. MCS thrombosis results from the interplay between haemodynamic conditions, biomaterial properties, and patient-specific pathologies; however, their interplay remains incompletely understood, and current in vitro thrombosis models often fail to integrate these factors under clinically relevant conditions.

This thesis developed a clinically guided microfluidic ECMO thrombosis-on-a-chip model that integrated customisable flow conditions, biomaterials, and healthy donor or patient blood samples, enabling high-throughput assessment of thrombosis mechanisms and screening the thrombogenicity of ECMO conditions. ECMO tubing-connector junctions, corresponding to flow gradients, were frequent sources of thrombosis in a retrospective observational study of patient circuits. The ECMO thrombosis-on-a-chip model mimicked this phenomenon, with platelet aggregate adhesion, growth, and embolism observed at flow gradients. Having validated the ability of the model to replicate clinical observations, further thrombotic effects elucidated by the model include that low shear rate and circuit stoppage increased platelet adhesion, polyvinyl chloride increased platelet activation compared to polycarbonate, polycarbonate and polyvinyl chloride increased platelet adhesion but decreased coagulation compared to polypropylene and polydimethylsiloxane, and ECMO patient blood samples showed less platelet adhesion compared to healthy donor samples.

Together, the novel medical device thrombosis-on-a-chip platform and its findings offer insights into thrombosis in ECMO and MCS, informing testing and design considerations for the next generation of MCS to reduce thrombotic and haemostatic complications in clinical practice.