Abstract

Traditional flow models have provided valuable insight into the mechanisms of arterial thrombosis. However, these models usually fail to simulate the occlusive thrombi that cause heart attacks and strokes. This limits the usefulness of these models in assessing new anti-thrombotic drugs. Murine artery injury models are often used, but they are limited by the inherent differences of human and mouse platelets. Thus, there is a need for a more biologically relevant in vitro model that uses human blood and more accurately replicates the arterial thrombosis seen in the human body.

We have developed an in vitro microfluidic model, using whole human blood, which reliably produces occlusive thrombi. The custom-designed microfluidic chamber has a branched structure and incorporates a line of high concentration EDTA to quench downstream coagulation. The antithrombotic drug eptifibatide has been tested in both EDTA -quenched and unquenched devices, and the results show a clear need for this addition if meaningful results are to be gained from these models.

This assay provides a robust and biologically relevant method for testing the ability of antithrombotics to prevent occlusive clot formation, and for exploring the mechanisms underlying arterial thrombosis.