Abstract Number: OC 52.4
Meeting: ISTH 2021 Congress
Background: Vascular injuries that penetrate or transect the vessel wall present a spatially heterogenous architecture to blood: an endothelial layer with pro- and anti-coagulant proteins, a vessel wall rich in platelet adhesive matrix proteins, and an extravascular environment rich in procoagulant proteins. Yet, in most in vitro models of hemostasis including ours (Schoeman, Cell. Mol. Bioeng., 2017), these proteins are presented to flowing blood as a homogenous mixture.
Aims: The objective of this study was to determine how the spatial presentation of thrombomodulin, collagen, and tissue factor affected thrombus formation and structure.
Methods: Recalcified citrated whole blood flow was perfused through a microfluidic channel (20 µm) at pressure drops that are comparable to the transvascular pressures (7.5-67.5 mmHg) of humans. Collagen related peptides (GFOGER, (GPO)n, VWF binding peptide), thrombomodulin, and/or tissue factor (TF) were patterned together a homogenous or segmented strips (Fig. 1). Platelet accumulation (DiOC6) and activation (anti-P-selectin), and fibrin (AlexaFluor647-fibrinogen) were measured by spinning disc confocal microscopy and time to occlusion was measured with a flow meter connected to the device.
Results: We observe differences in thrombus architecture, thrombus kinetics, and time to occlusion when patterning collagen related peptides and TF in a homogenous versus a segmented configuration (Fig. 1). Thrombi formed on a homogenous pattern had a faster time-to-occlusion compared to a segmented pattern, and show different spatial and temporal buildup of activated platelets and fibrin (Fig 1). In segmented patterning, significant platelet accumulation is required before fibrin formation begins, whereas in homogenous patterning fibrin formation occurs almost immediately after initial platelet adhesion.
Conclusions: These findings demonstrate the role the spatial presentation of pro- and anticoagulant proteins plays in dictating thrombus structure and growth.
To cite this abstract in AMA style:Sorrells M, Neeves K. Deconstructing the Role of Vessel Wall Architecture on Hemostasis in a Microfluidic Model of Microvascular Bleeding [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/deconstructing-the-role-of-vessel-wall-architecture-on-hemostasis-in-a-microfluidic-model-of-microvascular-bleeding/. Accessed September 24, 2021.
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