Abstract Number: PB1034
Meeting: ISTH 2021 Congress
Background: Hemostatic clots have a P-selectin positive core surrounded by a P-seletctin negative shell where P2Y12 activation is necessary for platelet recruitment.
Aims: To understand the contribution of P2Y12 signaling to core/shell mechanics and stability in human thrombi utilizing a 2-step microfluidic assay.
Methods: A 2-stage assay perfused whole blood over a collagen/ tissue factor surface at a wall shear rate of 100 s-1 followed by perfusion of a buffer at 1000 s-1. A P2Y12 antagonist was utilized to block ADP binding to the integrin. Platelet deposition and P-selectin expression are measured with immunofluorescence.
Results: P2Y12 antagonism with 2-MeSAMP drastically lowers platelet aggregation and the number of P-selectin positive platelets when blood is perfused over a collagen/tissue factor when compared to the absence of 2-MeSAMP for 20 minutes. Occlusion is not reached with platelets constantly attaching and detaching from the thrombus. Utilizing an extended height 8-channel device, clot growth is immediately stopped when switching to buffer well before clot occlusion. When subjected to increase shear and switch to buffer at 180 s, 2-MeSAMP treated clots are highly unstable, and large platelet masses detach immediately. This is in contrast to control clots which erode at a much slower rate. 2-MeSAMP treated clots erode by almost 60% at 1200 s compared to 40% for control clots. P2Y12antagonism lowered the stability of P-selectin negative platelets while the P-selectin positive core region is stable under both conditions.
Conclusions: The 2-stage microfluidic assay allows for interrogation core/shell mechanics by stopping thrombus growth and then examining platelet-platelet interactions through the use of shear. P2Y12 antagonism greatly limits the formation of stable shell region while limiting core formation.
To cite this abstract in AMA style:DeCortin M, Diamond S. Investigation of Core and Shell Platelet Mechanics through P2Y12 Antagonism [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/investigation-of-core-and-shell-platelet-mechanics-through-p2y12-antagonism/. Accessed September 16, 2021.
« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/investigation-of-core-and-shell-platelet-mechanics-through-p2y12-antagonism/