Shear Effects on Blood-Protein Adhesion in Microfluidic Devices
Open Access
- Author:
- Ward, Shane
- Area of Honors:
- Biomedical Engineering
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Keefe B Manning, Thesis Supervisor
Meghan Vidt, Thesis Honors Advisor - Keywords:
- vWF
ADAMTS-13
Platelets
IFM
PIV - Abstract:
- Left ventricular assist devices (LVADs) are an established method of surgical intervention for patients with heart failure. The implementation of these devices has led to significantly improved survival rate, yet the current generation of devices also cause increased risk of numerous secondary pathologies or complications. Pathological blood flow causes many patients to exhibit a poor ability to maintain hemostasis. This can lead to complications such as gastrointestinal bleeding, stroke, or device-mediated thrombosis. A common disorder prevalent in LVAD patients is acquired von Willebrand syndrome (AVWS), which causes dysfunction of the blood protein von Willebrand factor (vWF). Recent studies have sought to understand the adverse effects of supraphysiological shear rates caused by a LVAD which impairs vWF function. Because vWF is an essential protein in shear-mediated clotting, it has been hypothesized that high shear rates cause excessive elongation and cleavage of vWF by the protein ADAMTS-13. Excessive cleavage of vWF results in the inability of vWF to adhere and recruit platelets at sites of vascular injury. This study was designed to understand how vWF and platelet adhesion to various substrates is driven by shear rates consistent with physiological circulation as well as the high shear of LVAD flow. This study hypothesizes that there exists a threshold at which von Willebrand factor is the primary cause of platelet adhesion, rather than integrin-surface interaction. Evidence of increased platelet adhesion due to hypershear is exhibited. Presence of ADAMTS-13 in pathological shear rates is shown to diminish the effect of vWF in platelet recruitment and even decrease platelet adhesion at lower shear rates.