Megakaryocyte-specific deletion of the Rap1a and Rap1b genes leads to macrothrombocytopenia. Flow cytometric analysis of the peripheral platelet count (A) and platelet size (forward scatter height [FSH]) (B) in mice lacking 1 or both alleles of the Rap1a and Rap1b genes in the platelet/megakaryocyte lineage, as indicated below each bar (n = 12). (C) Platelet lifespan assay. Endogenous platelets were labeled by infusion of Alexa Fluor 488–conjugated antibody to GPIX, and the percentage of GPIX-labeled platelets remaining was determined by flow cytometry every 24 hours. (D) In vitro proplatelet (PP) formation in bone marrow–derived megakaryocytes. (E) Representative images of megakaryocytes for PP-formation assay, acquired on an Olympus IX-81 wide-field microscope with a Photometrics CoolSnap HQ2 camera. *P < .05, **P < .01, ***P < .001. ns, not significant.