OC 09.5 - Role of disturbed blood flow in the intrinsic thrombogenicity of human carotid stents

Background: In around 20% of emergency endovascular procedures for acute anterior circulation stroke, there is a tight stenosis or occlusion of the cervical carotid artery in addition to intracranial arterial occlusion. Emergent stenting of the carotid leads to better recanalization rates and improved clinical outcomes, however, dual-antiplatelet therapy is often avoided due to increased risk of haemorrhagic transformation. Early stent thrombosis (ST) occurs frequently in these patients (up to 21%) and has been associated with worse clinical outcomes. A better understanding of the mechanism of ST could improve the clinical management of these patients and open new avenues for the development of less thrombogenic stents.

Aims: To evaluate the role of rheology in carotid ST.

Methods: We developed an on-scale macrofluidic flow chamber mimicking a human carotid artery to investigate the thrombogenicity of clinically-used stents. Hemodynamic profile was characterized using computational fluid dynamics (CFD). Platelet aggregation was studied using fluorescence and scanning electron microscopy (SEM).

Results: Real-time video-macroscopy showed that anticoagulated whole blood perfused at physiological shear rates found in the human carotid, resulted in an accumulation of platelet thrombi on the stent struts within the first hour. SEM indicated that platelets adherent to the stents were activated as indicated by their shape change and filopodia extension. Interestingly, regions of platelet aggregation were not randomly distributed, and hot spots of thrombus formation were identified around the crossing of the stent mesh, suggesting a pivotal role of local rheology rather than the stent material. CFD allowed to precisely characterize the flow occurring at these hot spots and identify thrombogenic flow profiles. The use of anti-platelet drugs and pharmacological agents identified integrin alphaIIbbeta3 as a trigger of thrombus formation on the stent struts.

Conclusion(s): Our results highlight the pro-thrombogenic potential of local stent-mediated blood flow disturbances and open ways to better prevent their occurrence.