Thromboprophylaxis in Extracorporeal Circuits: Current Pharmacological Strategies and Future Directions

The development of extracorporeal devices for organ support has been a part of medical history and progression since the late 1900s. These types of technology are primarily used and developed in the field of critical care medicine. Unfractionated heparin, discovered in 1916, has really been the only consistent form of thromboprophylaxis for attenuating or even preventing the blood-biomaterial reaction that occurs when such technologies are initiated. The advent of regional anticoagulation for procedures such as continuous renal replacement therapy and plasmapheresis have certainly removed the risks of systemic heparinization and heparin effect, but the challenges of the blood-biomaterial reaction and downstream effects remain. In addition, regional anticoagulation cannot realistically be applied in a system such as extracorporeal membrane oxygenation because of the high blood flow rates needed to support the patient. More recently, advances in the technology itself have resulted in smaller, more compact extracorporeal life support (ECLS) systems that can-at certain times and in certain patients-run without any form of anticoagulation. However, the majority of patients on ECLS systems require some type of systemic anticoagulation; therefore, the risks of bleeding and thrombosis persist, the most devastating of which is intracranial hemorrhage. We provide a concise overview of the primary and alternate agents and monitoring used for thromboprophylaxis during use of ECLS. In addition, we explore the potential for further biomaterial and technologic developments and what they could provide when applied in the clinical arena.