Shear-dependent platelet aggregation size.

Area of Science:

• Biomedical Engineering
• Hematology
• Cardiovascular Science

Background:

• Nonsurgical bleeding is a frequent complication in patients with left ventricular assist devices (LVADs).
• Supraphysiologic shear rates generated by LVADs can impair platelet aggregation, elevating bleeding risk.
• The impact of shear rate on platelet aggregate size, a critical factor in bleeding, remains understudied.

Purpose of the Study:

• To investigate the effect of varying shear rates and exposure times on platelet aggregate formation size.
• To determine the relationship between shear rate, von Willebrand factor (vWF) multimer integrity, and platelet aggregation.
• To elucidate the mechanisms (mechanical shear vs. ADAMTS13) contributing to reduced platelet aggregation under shear stress.

Main Methods:

• Human platelet-poor plasma with vWF and labeled platelets were subjected to shear rates from 0 to 10,000 s⁻¹ for up to 15 minutes using a custom blood-shearing device.
• Platelet aggregate sizes were measured using microscopy.
• High molecular weight (HMW) vWF multimers were quantified via gel electrophoresis and immunoblotting; inhibition studies explored mechanical and enzymatic effects.

Main Results:

• Platelet aggregates were significantly larger at physiological shear rates (360–3000 s⁻¹) compared to high shear rates (>6000 s⁻¹).
• Increased shear rates led to a reduction in HMW vWF multimers.
• Inhibition studies indicated that ADAMTS13 was the primary mediator of reduced platelet aggregation size and HMW vWF multimer loss.

Conclusions:

• Shear rates exceeding 6000 s⁻¹ significantly reduce platelet aggregate size, compromising their ability to form effective plugs.
• Maintaining shear rates below this threshold is essential for preserving platelet function and preventing bleeding in LVAD patients.
• ADAMTS13 plays a critical role in mitigating shear-induced platelet dysfunction and vWF degradation.