Cerebral ischemia-reperfusion injury induces the formation of circulating necrotic PNAs. Male and female CypD^plt−/− mice or littermate controls (CypD^plt+/+) were subjected to 1 hour of cerebral ischemia, followed by 23 hours of reperfusion via tMCAO. Twenty-four hours after tMCAO, PMAs (A), PNAs (B), and PS⁺ platelets within PNAs (C) were quantified by flow cytometry. P-selectin (D) and GPIb-α (E) expression on platelets was analyzed by flow cytometry immediately before and 24 hours after ischemic stroke. (F) Platelets and neutrophils were isolated from CypD^plt+/+ and CypD^plt−/− mice and activated with dual agonists against PAR4 and GPVI to induce platelet necrosis. PNAs were then imaged by TEM (panels are representative of n = 3 mice per group). Yellow arrows indicate necrotic platelets. ns, not significant.