The mechanisms of cGMP-induced biphasic platelet responses. Elevation of cGMP levels in platelets induces an early phase stimulatory platelet response, promoting platelet aggregation induced by certain agonists such as thrombin and VWF.^5,6  This response is mediated via PKG-ERK signaling pathway.^5,6  Subsequently, cGMP, possibly by inhibiting phosphodiesterase 3, causes elevation of cAMP in human platelets, activating PKA. PKA, by inducing phosphorylation of VASP and other intracellular molecules, plays a predominant role in inhibition of platelets, preventing overgrowth of hemostatic thrombus. In platelets stimulated with collagen, however, PKG is also involved in the inhibitory phase of cGMP effect in addition to a predominant role of PKA.¹⁹  PKG is important in the inhibitory phase of cGMP in collagen-induced mouse platelet aggregation and cGMP analog–induced VASP phosphorylation in mouse platelets.²⁵