Apoptotic versus procoagulant platelets: similar "necrotic" phenotype and procoagulant activity in vitro, but...

Platelets can undergo at least two distinct types of regulated cell death, apoptosis and mPTP-driven necrosis. Apoptosis is believed to be responsible for platelet clearance, while strong platelet activation by physiological agonists leads to necrosis, producing procoagulant platelet remnants that are essential for blood coagulation during thrombosis and hemostasis. To thoroughly compare morphological and functional features of apoptotic and necrotic-like procoagulant platelets in vitro, their procoagulant activity, ability to bind coagulation proteins, and adhesive protein composition were evaluated. Confocal and electron microscopy were used to analyze morphology. Both apoptotic and necrotic-like procoagulant platelets had balloon-shaped morphology with phosphatidylserine-enriched "caps", as well as similar abilities to bind blood coagulation factors and participate in procoagulant reactions. However, apoptotic platelets did not release their alpha-granules and, consequently, did not have the "coat" of alpha-granular proteins such as P-selectin, fibrin(ogen), and von Willebrand factor on their surface, which was characteristic for the necrotic-like procoagulant ones. They were completely unable to bind external fibrinogen. They were completely unable to bind external fibrinogen. During storage of platelet concentrates, PS-positive platelets of both apoptotic (PS⁺/CD62P^-) and necrotic-like procoagulant (PS⁺/CD62P⁺) phenotypes were observed to accumulate.