Biphasic roles of sGC in regulating platelet activation. Physiologic platelet agonists such as thrombin and collagen activate sGC through NOS-dependent or -independent pathways, leading to platelet activation and formation of a hemostatic thrombus. Continued cGMP elevation in aggregated platelets or NO donors induces a second phase of inhibitory cGMP signaling, resulting in inhibition of further recruitment of platelets. This prevents the overgrowth of hemostatic thrombus.