Direct Observation of von Willebrand Factor Elongation and Fiber Formation on Collagen During Acute Whole Blood Exposure to Pathological Flow

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Abstract

Objective—

In severe stenosis, von Willebrand Factor (vWF) experiences millisecond exposures to pathological wall shear rates (γw). We sought to evaluate the deposition of vWF onto collagen surfaces under flow in these environments.

Methods and Results—

Distinct from viscometry experiments that last many seconds, we deployed microfluidic devices for single-pass perfusion of whole blood or platelet-free plasma over fibrillar type 1 collagen (<50 ms transit time) at pathological γw or spatial wall shear rate gradients (grad γw). Using fluorescent anti-vWF, long thick vWF fibers (>20 μm) bound to collagen were visualized at constant γw>30000 s–1 during perfusion of platelet-free plasma, a process enhanced by EDTA. Rapid acceleration or deceleration of EDTA platelet-free plasma at grad γw=±1.1×105 to ±4.3×107 s–1/cm did not promote vWF deposition. At 19400 s–1, EDTA blood perfusion resulted in rolling vWF–platelet nets, although blood perfusion (normal Ca2+) generated large vWF/platelet deposits that repeatedly embolized and were blocked by anti-glycoprotein Ib or the αIIbβ3 inhibitor GR144053 and did not require grad γw. Blood perfusion at venous shear rate (200 s–1) produced a stable platelet deposit that was a substrate for massive but unstable vWF–platelet aggregates when flow was increased to 7800 s–1.

Conclusion—

Triggered by collagen and enhanced by platelet glycoprotein Ib and αIIbβ3, vWF fiber formation occurred during acute exposures to pathological γw and did not require gradients in wall shear rate.

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