Phosphatidylserine (PS) on activated platelets (PS)

Anionic phospholipid surfaces, predominantly phosphatidylserine (PS), are essential components of the cell-based model of coagulation (Lentz, 2003, PMID: 12837069). In quiescent platelets, PS is maintained on the inner membrane leaflet by flippases, but platelet activation triggers its translocation to the outer leaflet, a process mediated by scramblases (Zwaal et al., 2005, PMID: 15913654). This exposed anionic surface provides a high-affinity scaffold for the assembly of the tenase (factors IXa/VIIIa) and prothrombinase (factors Xa/Va) complexes, which are required for the explosive generation of thrombin (Heemskerk et al., 2013, PMID: 23303373). Because PS exposure is relatively restricted to activated platelets and damaged cells, it serves as a selective target for antithrombotic agents like Diannexin, which mask the surface to prevent clot propagation without necessarily inhibiting initial platelet adhesion (Rand et al., 2004, PMID: 15153459). Additionally, PS-targeting ligands are utilized in molecular imaging to detect thrombi and monitor cell death in various pathologies (Post et al., 2002, PMID: 12163644).

Other names

Anionic phospholipidsProcoagulant phospholipidsExposed phosphatidylserinePlatelet procoagulant surfacePhosphatidylserine

The primary mechanism involves the steric hindrance of coagulation factor binding. By binding with high affinity to the exposed phosphatidylserine headgroups, agents like Annexin A5 or Diannexin prevent the assembly of the tenase and prothrombinase complexes on the platelet surface, thereby halting the conversion of prothrombin to thrombin (Rand, 2000, PMID: 10807119).