Schematic diagram depicting neutrophils and platelets reaching the inflamed endothelium, where migrating platelets become arrested on the exposed subendothelial collagen at neutrophil extravasation sites, which generates endothelial breaches. Collagen-arrested platelets turn procoagulant upon receiving costimulatory mechanosensing signals from GPIIb/IIIa-Gα₁₃ and GPVI. Syk is activated downstream of GPVI, and supramaximal calcium bursts and CypD-dependent mitochondrial permeability transition pore (mPTP) opening causes mitochondrial depolarization (ΔΨm). This culminates in membrane translocase TMEM16F-mediated PS exposure. PS-assisted assembly of coagulation factors (CFs) on procoagulant platelets drives thrombin generation that results in the formation of fibrin-enriched microthrombi, which restores vascular integrity. However, a potential role of von Willebrand factor (VWF)—GPIb-mediated mechanosensing on the sequential transition of GPIIb/IIIa affinity from a closed to an intermediate extended-closed state essential to mediate mechanotransduction, and eventually to an extended-open state—remains to be deciphered. Illustration was created with the help of Servier Medical art: https://smart.servier.com.