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Phosphatidylserine-enriched platelet membranes are specialized surfaces that appear on the exterior of platelets following activation or during apoptosis (Bevers & Williamson, 2016). Under normal physiological conditions, phosphatidylserine (PS) is maintained on the inner leaflet of the cell membrane by ATP-dependent flippases. Upon stimulation by potent agonists like thrombin and collagen, PS is translocated to the outer leaflet via the action of scramblases, creating a procoagulant surface (Lentz, 2003). This externalized PS provides a high-affinity, negatively charged platform for the assembly of the tenase and prothrombinase complexes, which are essential for the rapid generation of thrombin (Heemskerk et al., 2013). Because of its central role in the coagulation cascade, this membrane state is a significant target for antithrombotic therapies and diagnostic imaging. Drugs such as Annexin A5 and its derivatives bind specifically to exposed PS to inhibit the assembly of coagulation factors or to localize imaging agents to active thrombi. Furthermore, the presence of PS-enriched membranes on platelets and microparticles is a key biomarker for prothrombotic states in various cardiovascular and inflammatory diseases. Therapeutic antibodies like bavituximab also target exposed PS in the tumor microenvironment and viral infections, where PS exposure is a common feature of stressed or infected cells.
Binding to exposed phosphatidylserine on the platelet surface to sterically inhibit the assembly of the tenase and prothrombinase complexes, thereby reducing thrombin generation.
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