Thrombotic response to mechanical circulatory support devices

Cardiovascular mechanical circulatory support (MCS) device use triggers thrombosis and hemostatic disorders, which may become fatal if thrombi occlude circulation or cause embolic complications. Consequently, antithrombotic medications are administered, which often cannot eliminate thrombosis and further compromise patient survival by introducing an additional risk of severe bleeding events. MCS thrombosis is induced and affected by the combined interplay of patient pathology, the foreign artificial biomaterial's surface properties, and pathological flow conditions. From a device design perspective, the latter 2 may be controlled for and redesigned to minimize the thrombotic response. This review examines how MCS thrombosis is affected by the biomaterial properties of surface roughness and topography, chemistry and charge, wettability, and bioactive coatings and the hemodynamic flow properties of margination, low flow and coagulation, high flow and platelet activation, von Willebrand factor activation, and hemolysis. For each property, we explain its well-established underlying biological, chemical, or physical effects on thrombosis and highlight current and proposed design strategies that could reduce MCS thrombosis. We review the potential reasons thrombosis still complicates MCS devices and postulate that an improved understanding of the dominant thrombotic process occurring at specific regions of devices and mechanistic insights into the combined effects of material properties with flow are still required. Together, we provide a guide for potential biomaterial and flow design changes to reduce thrombosis in MCS, emphasizing that novel biomaterials and device geometries should be tested under operationally and clinically relevant flow conditions to develop safer future-generation devices with reduced thrombotic responses.