VPB0900 - Platelets and von Willebrand factor after exposure to turbulent, but low shear flow with implications in mechanical circulatory support

Background: Heart failure is a major cause of death with the gold standard of treatment being heart transplantation. However, there are various limitations to this solution including patient eligibility and donor supply. Despite its many benefits, VADs exhibit significant limitations in hemocompatibility. Many ventricular assist devices (VADs) introduce turbulent flow characteristics, leading to detrimental effects on various blood components including platelets and proteins, such as von Willebrand factor (VWF).

Aims: Aim 1 (Evaluate effects of turbulent flow on VWF cleavage): We hypothesize that the increase in rotational speed and presence of turbulent flow will increase VWF cleavage.
Aim 2 (Evaluate effects of turbulent flow on platelet activation): We hypothesize that the increase in rotational speed and turbulent flow will increase platelet activation.

Methods: We will draw peripheral whole blood and separate out the red blood cells to isolate plasma proteins and platelets. After isolation, we will expose platelet poor plasma to three different flow conditions calculated by preliminary results, followed by a multimer blot to assess VWF cleavage.
To evaluate platelet activation after samples are exposed to vortexing, we will use flow cytometry to assess integrin (alpha)IIb(beta)3 conformational change CD41 expression and p-selectin release by CD62 expression.

Results: Our results demonstrate the power of a simple vortexer assay in studying biological samples in a complex flow environment without requiring large sample. Although we are not the first to use this assay, we are the first to our knowledge to fully investigate the role of turbulence that can be created through this assay.

Conclusion(s): Our findings provide the field with a better understanding of the flow conditions that lead to VWF extension and cleavage in addition to platelet activation found in turbulence. This lays the groundwork for improving designs of blood-contacting mechanical devices resulting in a lowered risk of bleeding and clotting complications after device implantation.