MCS Shear-Medicated Platelet Activation Does not Cause Integrin GPIIbIIIa Activation, Rather Shedding and Microparticle Generation

Roka‐Moiia, Yana; Palomares, Daniel E.; Sheriff, Jawaad; Bluestein, Danny; Slepian, Marvin J.

doi:10.1016/j.healun.2018.01.392

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“…A prime driver, pathophysiologically, of many of these adverse hemocompatibility‐related events relates to abnormal, supraphysiologic shear stresses imparted to circulating blood within the MCS device . Elevated shear stress accumulation (SA) leads to shear‐mediated platelet activation (SMPA), driving thrombosis and denaturation of von Willebrand factor, as well as other blood alterations, contributing to bleeding and disordered blood homeostasis …”

Section: Introductionmentioning

confidence: 99%

Circulatory loop design and components introduce artifacts impacting in vitro evaluation of ventricular assist device thrombogenicity: A call for caution

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Roka‐Moiia

et al. 2020

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Mechanical circulatory support (MCS) devices continue to be hampered by thrombotic adverse events (AEs), a consequence of device-imparted supraphysiologic shear stresses, leading to shear-mediated platelet activation (SMPA). In advancing MCS devices from design to clinical use, in vitro circulatory loops containing the device under development and testing are utilized as a means of assessing device thrombogenicity. Physical characteristics of these test circulatory loops may also contribute to inadvertent platelet activation through imparted shear stress, adding inadvertent error in evaluating MCS device thrombogenicity. While investigators normally control for the effect of a loop, inadvertent addition of what are considered innocuous connectors may impact test results. Here, we tested the effect of common, additive components of in vitro circulatory test loops, that is, connectors and loop geometry, as to their additive contribution to shear stress via both in silico and in vitro models. A series of test circulatory loops containing a ventricular assist device (VAD) with differing constituent components, were established in silico including: loops with 0~5 Luer connectors, a loop with a T-connector creating 90° angulation, and a loop with 90° angulation. Computational fluid dynamics (CFD) simulations were performed using a k − shear stress transport turbulence model to platelet activation index (PAI) based on a power law model. VAD-operated loops replicating in silico designs were assembled in vitro and gel-filtered human platelets were recirculated within (1 hour) and SMPA was determined. CFD simulations demonstrated high shear being introduced at non-smooth regions such as edge-connector boundaries, tubing, and at Luer holes. Noticeable peaks' shifts of scalar shear stress (sss) distributions toward high shear-region existed with increasing loop complexity. Platelet activation also increased with increasing shear exposure time, being statistically higher when platelets were exposed to connector-employed loop designs.The extent of platelet activation in vitro could be successfully predicted by CFD simulations. Loops employing additional components (non-physiological flow pattern connectors) resulted in higher PAI. Loops with more components (5-connector loop and 90° T-connector) showed 63% and 128% higher platelet activation levels, respectively, versus those with fewer (0-connector (P = .023) and a 90° heat-bend

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Section: Introductionmentioning

confidence: 99%