Abstract
Mechanical circulatory support devices (MCSDs), although proved to be a pillar in the clinical setting of advanced heart failure, are afflicted by thromboembolic complications. Shear-mediated platelet activation has been recognized to drive thromboembolic events in patients implanted with MCSDs. Despite this, to date, a clinically reliable diagnostic test for assessing platelet response to stress stimuli is still missing. Here, we describe and apply the previously developed device thrombogenicity emulation methodology to the design of a microfluidic platform able to replicate shear stress profiles representative of MCSDs. The device-specific shear-mediated platelet activation is finally assessed by the platelet activity state assay, which measures real-time thrombin production, as a marker of platelet activation level. This technique can be employed to emulate the shear stress patterns of different MCSDs, such as mechanical heart valves, ventricular assist devices, and stents.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Stewart GC, Givertz MM (2012) Mechanical circulatory support for advanced heart failure: patients and technology in evolution. Circulation 125(10):1304–1315
Kirklin JK, Naftel DC, Pagani FD et al (2014) Sixth INTERMACS annual report: a 10,000-patient database. J Heart Lung Transplant 33(6):555–564
Chen Z, Zhang J, Kareem K et al (2019) Device-induced platelet dysfunction in mechanically assisted circulation increases the risks of thrombosis and bleeding. Artif Organs 43(8):745–755
Tarzia V, Buratto E, Bortolussi G et al (2014) Hemorrhage and thrombosis with different LVAD technologies: a matter of flow? Ann Cardiothorac Surg 3(6):582–584
Roudaut R, Serri K, Lafitte S (2007) Thrombosis of prosthetic heart valves: diagnosis and therapeutic considerations. Heart 93(1):137–142
Bonacchi M, Harmelin G, Bugetti M, Sani G (2015) Mechanical ventricular assistance as destination therapy for end-stage heart failure: has it become a first line therapy? Front Surg 2:35
Garbade J, Bittner HB, Barten MJ, Mohr FW (2011) Current trends in implantable left ventricular assist devices. Cardiol Res Pract 2011:290561
Slaughter MS, Rogers JG, Milano CA et al (2009) Advanced heart failure treated with continuous-flow left ventricular assist device. New Eng J Med 361(23):2241–2251
Bluestein D (2004) Research approaches for studying flow-induced thromboembolic complications in blood recirculating devices. Expert Rev Med Devices 1(1):65–80
Girdhar G, Xenos M, Alemu Y et al (2012) Device thrombogenicity emulation: a novel method for optimizing mechanical circulatory support device thromboresistance. PLoS One 7(3):1–10
Colace TV, Tormoen GW, McCarty OJT, Diamond SL (2013) Microfluidics and coagulation biology. Ann Rev Biomed Eng 15:283–303
Neeves KB, Onasoga AA, Wufsus AR (2013) The use of microfluidics in hemostasis: clinical diagnostics and biomimetic models of vascular injury. Curr Opin Hematol 20(5):417–423
Sakariassen KS, Turitto VT, Baumgartner HR (2004) Recollections of the development of flow devices for studying mechanisms of hemostasis and thrombosis in flowing whole blood. J Thromb Haemost 2(10):1681–1690
Thamsen B, Blümel B, Schaller J et al (2015) Numerical analysis of blood damage potential of the HeartMate II and HeartWare HVAD rotary blood pumps. Artif Organs 39(8):651–659
Velve-Casquillas G, La Berre M, Piel M et al (2010) Microfluidic tools for cell biological research. Nano Today 5(1):28–47
Dimasi A, Rasponi M, Sheriff J et al (2015) Microfluidic emulation of mechanical circulatory support device shear-mediated platelet activation. Biomed Microdevices 17:117
Consolo F, Dimasi A, Rasponi M et al (2016) Microfluidic approaches for the assessment of blood cell trauma: a focus on thrombotic risk in mechanical circulatory support devices. Int J Artif Organs 39(4):184–193
Bluestein D, Girdhar G, Einav S, Slepian MJ (2013) Device thrombogenicity emulation: a novel methodology for optimizing the thromboresistance of cardiovascular devices. J Biomech 46(2):338–344
Jesty J, Bluestein D (1999) Acetylated prothrombin as a substrate in the measurement of the procoagulant activity of platelets: elimination of the feedback activation of platelets by thrombin. Anal Biochem 272(1):64–70
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Mencarini, T., Bozzi, S., Redaelli, A. (2022). On-Chip Platelet Activation Assessment: Microfluidic Emulation of Shear Stress Profiles Induced by Mechanical Circulatory Support Devices. In: Rasponi, M. (eds) Organ-on-a-Chip. Methods in Molecular Biology, vol 2373. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1693-2_12
Download citation
DOI: https://doi.org/10.1007/978-1-0716-1693-2_12
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-1692-5
Online ISBN: 978-1-0716-1693-2
eBook Packages: Springer Protocols