Gas6 (G6) exerts prothrombotic properties in the hematopoietic and vascular compartments. Shown is a highly simplified cartoon model of effects of Gas6 on platelets and endothelial cells. As platelets adhere and activate on contact with damaged endothelial cells (not shown), platelet aggregation is achieved through synergistic intracellular signaling events that are mediated by Gas6-TAM and ADP-P2Y₁₂ interactions. These induce activation of PI3-kinase that in turn, leads to sustained activation of αIIbβ3 and engagement with fibrinogen. Thrombin (IIa), presumably acting via one of the protease activated receptors (PAR), induces the release of Gas6 from endothelial cells by unknown mechanisms. Gas6 that is released (or circulating) subsequently binds to one of the TAMs, which leads to up-regulation of tissue factor (TF), again via unknown mechanisms. TF can then initiate coagulation, first by binding to factor VIIa, ultimately leading to further thrombin generation and the formation of a fibrin clot (not shown). Relative sources of Gas6 have not been elucidated, and there is likely cross-talk between cells. The possible contribution of smooth muscle cells and other circulating cells is not shown.