Relative Contributions of von Willebrand Factor and Platelets in High Shear Thrombosis
- *Corresponding Author:
- David N Ku
MD, PhD, GWW School of Mechanical Engineering
Georgia Institute of Technology
315 Ferst Dr., Room 2307Atlanta
E-mail: [email protected]
Received date: July 31, 2016; Accepted date: August 12, 2016; Published date: August 19, 2016
Citation: Casa LDC, Gillespie SE, Meeks SL, Ku DN (2016) Relative Contributions of von Willebrand Factor and Platelets in High Shear Thrombosis. J Hematol Thrombo Dis 4:249. doi: 10.4172/2329-8790.1000249
Copyright: © 2016 Casa LDC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Platelets and von Willebrand factor (VWF) are recognized as important mediators of thrombosis at high shear rates, but their relative contributions are unclear. We employ a stenotic microfluidic test system to induce thrombus formation to occlusion on collagen at pathologic shear rates of 3500-6000 s-1. To obtain blood analogs with reduced platelet and VWF concentrations, human whole blood was diluted with saline by 90% or 99% and hematocrit restored by adding washed red blood cells. Platelets and VWF were selectively restored to normal levels. Blood from patients with known von Willebrand disease (VWD) was also investigated with and without the addition of VWF to investigate the contribution of platelet VWF. Normal whole blood led to channel occlusion in all tests (occlusion time, tocc=6.1 ± 2.2 min). 90% dilution with restored VWF occluded in 6/7 subjects even without restored platelets (tocc=16.6 ± 1.4 min). 90% dilution with restored platelets occluded in 2/5 subjects (tocc=27.2 ± 1.8 min), showing that added VWF is more effective for restoring occlusion than platelets. Addition of plasma VWF to VWD blood restored occlusion in only 1/4 severe subjects (VWF:RCo<15) and did not reduce normal occlusion time in the occluding subject, suggesting that VWF release from platelets plays an important role in high shear thrombosis. Logistic regression shows that VWF concentration and platelet count are strong predictors of thrombotic occlusion. Efforts to control high shear thrombosis may focus on VWF in addition to platelet function.