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Phospholipid membranes of activated platelets are essential for the propagation of the coagulation cascade (Lentz, 2003). In resting platelets, anionic phospholipids, specifically phosphatidylserine (PS), are maintained on the inner leaflet of the cell membrane by flippase enzymes. Upon activation by agonists like thrombin or collagen, platelets undergo a loss of membrane asymmetry, exposing PS on the external surface via the action of scramblase (Heemskerk et al., 2013). This exposed PS acts as a high-affinity binding site for vitamin K-dependent clotting factors, facilitating the assembly of the tenase and prothrombinase complexes. These complexes are responsible for the explosive generation of thrombin, leading to fibrin formation and stable clot development. Therapeutically, these membranes are targeted to inhibit thrombosis or to image active thrombi (Kenis & Reutelingsperger, 2009). Agents like Annexin A5 bind to the exposed PS, sterically blocking the binding of coagulation factors and thereby exerting an anticoagulant effect. This target is particularly relevant in conditions like myocardial infarction, stroke, and deep vein thrombosis where pathological platelet activation occurs.
Binding to negatively charged phospholipids (primarily phosphatidylserine) to sterically inhibit the assembly of coagulation factor complexes such as tenase and prothrombinase.
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