Summary of mechanism of formation and action of 12-HETE-PLs in human platelets. (A) The 12-HETE-PLs are generated in response to thrombin activation of PAR1 and PAR4, via several signaling intermediates. Hydrolysis of arachidonate by cPLA2 is required. (B) Some HETE-PEs translocate to the outside of the plasma membrane and can enhance tissue factor-dependent thrombin generation. sPLA₂ indicates secretory phospholipase A₂; FACL, fatty acyl CoA ligase; and PLC, phospholipase C.