In vivo phenotype of mice lacking RGS10/18 or other platelet molecular brakes. Key features of the in vivo phenotype of mice lacking critical molecular brakes of platelets are (1) increased platelet accumulation at sites of injury, (2) increased platelet clearance, and (3) thrombocytopenia. Double deficiency of RGS10 and RGS18 results in an exaggerated thrombus growth and in a mild thrombocytopenia, which is in part due to increased platelet clearance, and in part due to a nonredundant contribution of RGS18 to the regulation of platelet production. The phenotype of other molecular brakes, RASA3 and G6b-B, is shown for comparison. Symbols indicate whether a knockout mouse (ko) displays an increased (↑), decreased (↓), or unaltered (=) phenotype. The inlet shows the 2 main G protein switches that control rapid agonist-induced platelet adhesion: (1) RGS10/18 negatively regulates the heterotrimetic G proteins coupled to surface receptors (GPCRs) stimulated by soluble agonists such as thrombin (Thr), thromboxane A2 (TxA2), and adenosine diphosphate (ADP); (2) RASA3 negatively regulates the monomeric G protein RAP1, critical regulator of integrin-mediated adhesion. MK, megakaryocyte.