Medical device-induced thrombosis : state of the art and new prevention strategies

Details

Supervisors

DOUXFILS JONATHAN ; EVRARD, Jonathan

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences pharmaceutiques

Abstract

Blood-contacting medical devices such as catheters, stents, vascular grafts and heart valves are often associated with thrombotic complications. In contrast to the anti-thrombotic properties of endothelial cells, artificial surface promote clotting by a process which involves protein adsorption followed by adhesion of platelets, leukocytes and red blood cells. Furthermore, the contact pathway of coagulation has been identified to play a major role in thrombosis induced by medical devices. Complement system is also involved by the activation of the classical and alternative pathways. To date, no material has been found truly hemocompatible for long-term use. Methods to prevent this process include structure modification of the surface and systemic anticoagulation. Surface modification include biochemical modifications and recently, tissue engineering approaches. On the other hand, pharmacological inhibition of the key enzymes responsible of the cascade reactions have been employed to prevent thrombosis on such devices. Modest efficacy associated with the bleeding risk of agents used nowadays show the need for new prevention strategies. Thereby the increasing recognition of the role of the intrinsic pathway of coagulation, particularly factor XI and factor XII , have been identified as potential targets. This essay firstly describes the underlying mechanisms of clotting on blood-contacting medical devices. Then, it presents and compares molecules used for prevention strategies. Finally, new strategies have been explored.