Abstract 40: Platelet Fragmentation During the Hemostatic Response and its Prevention by a P2Y12 Antagonist

• DOI: 10.1161/atvb.37.suppl_1.40
• Publication Date: 2021-07-02T23:44:11Z
• Authors: Maurizio Tomaiuolo; Chelsea N Matzko; Izmarie Poventud-...; Leonard Nettey; Brad A Herbig; John W Weisel; Scott L Diamond; Lawrence F Brass; Timothy J Stalker
• Keywords: Fragmentation

Previous studies using intravital microscopy have shown that hemostatic plugs formed in the mouse microvasculature a characteristic architecture which extent of platelet activation reflects gradients distribution agonists radiating outwards from injury site. In setting, we found minimal overlap thrombin and ADP signaling, with primarily responsible for robust close to site P2Y 12 -mediated signaling resulting accumulation minimally activated platelets. Here taken these major step forward by integrating fluorescence scanning electron microscopy. Hemostatic produced needle jugular veins were imaged situ 1 20 min after injury. The results show unprecedented detail what could only be inferred previously, showing size, morphology packing density vary remarkably depending on spatial localization within plug. intraluminal extravascular portions mass presented distinct architectures. A large comprised almost exclusively platelets was observed interior surface vein. Platelets closest edge had highly morphology, including P-selectin expression, dense fragmentation, while those farther often remained discoid. contrast, portion rich densely-packed, platelet-derived fragments intertwined fibrin. mice treated inhibitor significantly smaller. gradient described above less apparent and, notably, fragmentation not present. conclusion, our findings indicate 1) development is conserved feature response across different vessels, 2) occurs very rapidly following injury, 3) clinically relevant pathways play role regulating its formation.