Thrombus formation through upstream activation and downstream adhesion of platelets in a microfluidic system

초록

Activation of platelets tends to cause adhesion and aggregation of platelets to the vascular wall. In the circulatory environment, activation and adhesion may not occur at the same site since platelet activation requires time. Thus, we hypothesize that platelet activation at upstream and adhesion at downstream would be relevant in assessing the increased thrombotic risk associated with hyper-responsive vulnerable blood patients. In this study, we designed a highly integrated microfluidic flow system to mimic the hemodynamic environment of the vasculature with an upstream activation of platelets and downstream adhesion of platelets. Platelets can be activated by either agonists or shear stress generated with a rotational disk. The degree of platelet adhesion was monitored by the migration distance (MD) of blood through the microchannel until it was blocked. The degree of pre-activation was widely varied with incubation time, agonist concentration and shear stress levels, which directly affected downstream adhesion of preactivated platelets. There was a linear relation between degree of activation and that of adhesion. However, excessive activation, rather, degraded downstream adhesion of platelets due to upstream aggregation and platelet lysis. These results suggested that platelet adhesion was strongly dependent on the general conditions of upstream activation of platelets. This study implies that downstream thrombus formation may be caused by upstream platelet activation rather than on-site activation.