Investigation of shear dependent platelet aggregation

Abstract

This research investigates the shear rate dependence of platelet aggregation geometry and the characteristics of flow around fixed platelet aggregations to understand the role of fluid mechanics in cell adhesion and platelet aggregation mechanisms. It consists of three main parts. The first part of the research was an experimental investigation of local three-dimensional flow fields around fixed platelet aggregations using micro particle image velocimetry techniques. The local flow field was measured quantitatively at various constant upstream physiological shear rates to elucidate the actual shear stress experienced by adhering cells. Over the shear range examined, the out-of-plane shear rate was low immediately around platelet aggregations and increased gradually to the upstream shear rate moving away from the platelet aggregation. The in-plane shear rate was maximum around the sides of the platelet aggregation, and low at the front and rear. It is well established that platelets preferentially adhere in the region downstream of a growing platelet aggregation. The reason for this preferential adhesion was found to be that the platelet experiences a peak shear at the sides of the platelet aggregation, followed by a low shear downstream of the platelet aggregation. Moreover, the absolute velocity behind the platelet aggregation was relatively low and a small negative out-of-plane velocity component acted to push the platelets towards the wall. These factors provide favourable conditions for further platelet adhesion and aggregation in the region behind the growing platelet aggregation. The second part of the research explored the effect of shear rate on the final geometry of mature platelet aggregations and the evolution of platelet aggregation formation. It was shown that the height of mature platelet aggregations increased approximately linearly as the upstream shear rate increases. In addition, the idealised shear value at the platelet aggregation peak, calculated by the Poiseuille flow equation at that height, was approximately constant for the different upstream shear rates considered. The temporal analysis of platelet aggregation evolution revealed that the average platelet aggregation cross sectional shape changes from initially circular in cross section to the final elliptical cross section, conforming that platelets have a higher tendency to aggregate at the rear part of the existing platelet aggregation, where the shear is low. Moreover, the rate of platelet deposition on the rear part of a growing platelet aggregation was significantly higher than that occurring on top of the platelet aggregation. It is well understood that shear rate is a pivotal factor in initiating platelet aggregation. However, the effect of increasing upstream shear rate and time on the geometry of platelet aggregations revealed that shear rate is not only a primary factor in initiating platelet aggregation, but also is an important factor in regulating platelet aggregation growth. In addition, shear rate is one of the main inhibitors of platelet aggregation. It is proposed that when the platelets reach a critical height, they encounter specific local hemodynamic conditions, which prevents further platelet aggregation growth. The effect of pulsatile upstream flow on platelet aggregation properties is presented in the third part of the research. It is shown that pulsatile flow conditions significantly alter the aggregation of platelets. For flow pulsating at a rate nominally the same as a resting human heart, platelets were found to have a higher tendency to aggregate to form a thrombus when compared to steady flow conditions. The thrombus also grows more rapidly, becoming taller and larger under pulsatile flow condition. However, increasing the rate to be approximately that of an exercised human heart was found to reduce the number of thrombi and only a few aggregations form next to the micro-channel wall. For the first time experimental results show the dramatic alteration of platelet aggregation at pulsatile flow conditions. This may represent a paradigm shift in thrombus research.