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.
Highlights
Left ventricular assist device (LVAD) is a life-saving tool for providing haemodynamic support in patients with advanced, refractory left ventricular heart failure, either for temporary support, or as a permanent destination therapy [1, 2]
When platelets were exposed to higher shear rates at 6,000 s-1 and 10,000 s-1 for 15 min, the average platelet aggregate size decreased to 100.1 ± 8.2 μm2 and 65.7 ± 4.0 μm2 respectively
In supplemental figure 1, the result of flow cytometric investigation of Von Willebrand factor (vWF) function show that there were no significant differences in normalised platelet aggregation between the different shear conditions
Summary
Left ventricular assist device (LVAD) is a life-saving tool for providing haemodynamic support in patients with advanced, refractory left ventricular heart failure, either for temporary support (e.g. bridge to cardiac transplantation), or as a permanent destination therapy [1, 2]. The unfolded vWF exposes its A2 domains, which are sensitive to enzymatic cleavage by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) [9, 13, 14]. This causes excessive degradation of HMW vWF multimers. Such loss of HMW vWF caused by enzymatic cleavage of ADAMTS13 has been reported in in vitro LVAD evaluations [9, 15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
