Shear-dependent platelet aggregation size

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Chan, CHH
Inoue, M
Ki, KK
Murashige, T
Fraser, JF
Simmonds, MJ
Tansley, GD
Watanabe, N
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2020
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Abstract

Nonsurgical bleeding is the most frequent complication of left ventricular assist device (LVAD) support. Supraphysiologic shear rates generated in LVAD causes impaired platelet aggregation, which increases the risk of bleeding. The effect of shear rate on the formation size of platelet aggregates has never been reported experimentally, although platelet aggregation size can be considered to be directly relevant to bleeding complications. Therefore, this study investigated the impact of shear rate and exposure time on the formation size of platelet aggregates, which is vital in predicting bleeding in patients with an LVAD. Human platelet‐poor plasma (containing von Willebrand factor, vWF) and fluorochrome‐labeled platelets were subjected to a range of shear rates (0‐10 000 s−1) for 0, 5, 10, and 15 minutes using a custom‐built blood‐shearing device. Formed sizes of platelet aggregates under a range of shear‐controlled environment were visualized and measured using microscopy. The loss of high molecular weight (HMW) vWF multimers was quantified using gel electrophoresis and immunoblotting. An inhibition study was also performed to investigate the reduction in platelet aggregation size and HMW vWF multimers caused by either mechanical shear or enzymatic (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13—ADAMTS13, the von Willebrand factor protease) mechanism under low and high shear conditions (360 and 10 000 s−1). We found that the average size of platelet aggregates formed under physiological shear rates of 360‐3000 s−1 (200‐300 μm2) was significantly larger compared to those sheared at >6000 s−1 (50‐100 μm2). Furthermore, HMW vWF multimers were reduced with increased shear rates. The inhibition study revealed that the reduction in platelet aggregation size and HWM vWF multimers were mainly associated with ADAMTS13. In conclusion, the threshold of shear rate must not exceed >6000 s−1 in order to maintain the optimal size of platelet aggregates to “plug off” the injury site and stop bleeding.

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Artificial Organs

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© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc. This is the peer reviewed version of the following article: Shear‐dependent platelet aggregation size, Artificial Organs, which has been published in final form at https://doi.org/10.1111/aor.13783. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html)

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Biomedical engineering

Clinical sciences

ADAMTS13

Shear rate

exposure time

platelet aggregate

vWF

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Chan, CHH; Inoue, M; Ki, KK; Murashige, T; Fraser, JF; Simmonds, MJ; Tansley, GD; Watanabe, N, Shear-dependent platelet aggregation size, Artificial Organs, 2020

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