Fig. 1

a Different Stages of Platelet Adhesion to the Site of Vascular Injury. Resting platelets are initially captured on the site of vascular injury via the interaction between GPIb/V/IX and immobilized vWF (Tethering). Platelets firmly adhere to the sub-endothelial matrix through the engagement of collagen receptors α2β1 and GPVI (Adhesion). This triggers potent inside out signals inducing ADP release from dense bodies (Shape change & agonist release) as well as activating platelet major integrin α_IIbβ₃. Integrins facilitate platelet spreading and subsequent aggregation through the binding to vWF and fibrinogen. Activating signals down-stream engaged receptors induce the release of granule contents including P-selectin which provides an efficient scaffold for leukocyte recruitment linking pro-aggregatory phase of platelet activation to pro-inflammatory function. On the other hand, the accumulative signals further activate platelets and induce sustained calcium influx which results in the surface exposure of phosphatidylserine (PS) and pro-coagulant function leading to thrombin production and fibrin generation at the site of injury. Interacting with PAR receptors, generated thrombin also acts as a potent agonist which supports more efficient pro-inflammatory and pro-coagulant function. b Primary and secondary hemostasis: mutual links between pro-inflammatory and pro-coagulant function 1- (a) Followed by the injury, platelet recruitment to the exposed sub-endothelial matrix leads to the formation of a developing thrombus(b) which express either pro-inflammatory molecules (mainly P-selectin) or pro-coagulant phospholipids (primary hemostasis). 2- Pro-coagulant matrix presented by platelets provides an efficient scaffold for fibrin generation (a) which supports secondary hemostasis by the conversion of the white thrombus to a red clot containing a planner of fibrin network and trapped RBCs.3- Platelets recruits leukocyte(a) while during their crosstalk, neutrophils get fully activated and release their chromatin contents as extracellular NET(b). The negatively charged NET materials provide an efficient pro-coagulant scaffold for fibrin generation. 4-Platelets may also interact with generated fibrin while creating a secondary thrombus