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Biomechanics

Biomechanics - Poster Session B

Poster E4 - Elevated von Willebrand Factor and Dual Antiplatelet Therapy Impacts Thrombus Embolization Risk

Thursday, October 24, 2024
2:45 PM - 3:45 PM EST
Location: Exhibit Hall E, F & G

Introduction:  Some transient ischemic attack patients can still experience a recurrent stroke despite being on Dual Antiplatelet Therapy with ASA (aspirin) and P2Y12-inhibitor (ticagrelor). One pattern these patients have was an elevated von Willebrand Factor level (VWF), a blood protein that tethers platelets to endothelium and form blood clot. DAPT targets platelet activation by the coagulation cascade, specifically thromboxane A2 and P2Y12 receptor, but overlooks activation by binding with VWF and GPIb mechanotransduction. Even with DAPT, platelets can still bind to VWF via their surface receptor GPIb-IX-V under a high shear rate, forming a large platelet-plug subject to embolization from drag force. We hypothesize that embolization is more likely to happen in individuals with elevated VWF levels taking DAPT compared to individuals with normal VWF levels on the same medication; additionally, DAPT will decrease the contractile force of platelets, reducing its ability to resist drag force.

Materials and

Methods:  Our experimental conditions are: healthy whole blood, whole blood doped with 6-fold (50ug/mL) higher VWF level than the healthy level, whole blood doped with DAPT consists of 0.3mM ASA and 10uM P2Y12 inhibitor (DAPT), whole blood doped with 6-fold higher VWF level and DAPT. To test the hypothesis, we will: (1) use microfluidic devices to measure the force, area and activation level of the platelet-plugs in those four conditions and (2) still in progress, we are identifying which regions of platelet-plugs in the four conditions are prone to embolization by staining and tracking the movement of individual platelets as they form the plug.

Results, Conclusions, and Discussions: Regardless of DAPT, we saw platelet-plugs with elevated VWF levels have a larger area and are still activated. Among elevated VWF conditions, platelet-plugs with DAPT have lower contractile force than plugs without DAPT. We are in the process of analyzing individual platelet tracking data, but from observation a large amount of individual platelets detach in elevated VWF conditions compared to normal VWF conditions, both with and without DAPT. The result can shed light on impacts elevated VWF level can have to DAPT, potentially reshape the way individuals with ischemic stroke or transient ischemic attack are treated. In addition, it introduces the possibility of using the microfluidic device to screen patients for high VWF so antiplatelet therapies can be designed specific to any individual.

Acknowledgements (Optional):  Research reported in this publication was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number F31HL156697. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.