Abstract Number: PB0468
Meeting: ISTH 2020 Congress
Background: Hemorrhages occur in many situations, including disease- or drug-associated hemostasis failure, vessel diseases, and coagulopathies. Understanding the differences between the biological mechanisms of hemostasis and thrombosis is critical to the discovery of treatments to promote the former without adversely enhancing the latter. Current in vitro flow chamber-based models are adequately designed to study thrombosis yet not the biophysics of hemostasis.
Aims: Develop a microfluidic device to study the physical biology of hemostasis.
Methods: A polydimethylsiloxane-based microfluidic device was fabricated using photolithography consisting of two orthogonal channels: one for blood inlet (inlet channel) and the other (bleeding channel) to mimic the extravascular space that is exposed during vascular injury. A series of 3 pillars spaced 10 microns apart at the intersection of the channels acts as a model of endothelial barrier function. Only the bleeding channel is coated with extracellular matrix (ECM) proteins. Whole human recalcified blood was perfused through the device at a constant flow rate and time to occlusion, platelet deposition and fibrin formation were quantified.
Results: The bleeding channel occluded as a function of time, shear and ECM protein coating. Platelets aggregated at or behind the pillars in the bleeding channel as a function of shear rate. Blocking the common pathway of coagulation prevented the formation of hemostatic plug in the bleeding channel.
Conclusions: We are focused on characterizing the spatial dynamics and molecular mechanisms of the two essential hemostatic blood systems, thrombin generation and platelet activation, during hemostatic plug formation. Unique to our approach is the study of these processes in the context of the fluid dynamics relevant to hemostasis, spanning from theoretical to applied in vitro and in vivo approaches. Future work will involve developing a comprehensive model of blood transport during hemostasis through percolation theory of fluid dynamics.
To cite this abstract in AMA style:Lakshmanan HHS, Pore A, Shatzel JJ, Cristina P, Jurney P, Maddala J, Vanapalli SA, McCarty OJT. Development of a Microfluidic Pillar Device to Study Hemostasis in vitro [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/development-of-a-microfluidic-pillar-device-to-study-hemostasis-in-vitro/. Accessed January 23, 2022.
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