Impaired platelet clearance and platelet production. (A-C) Platelet half-life. The number of biotin⁺αIIbβ3⁺ platelets in the circulation of (A) Shp1 KO, (B) Shp2 KO, (C) Shp1/2 DKO, and Shp1 WT, Shp2 WT, and Shp1/2 WT mice were quantified daily pre-/postinjection of biotin-N-hydroxysuccinamide by flow cytometry (n = 4-8 mice/genotype per time point; mean ± SEM; ***P < .001). (D-E) Platelet recovery following immune-mediated thrombocytopenia. (D) Shp1 KO, (E) Shp2 KO, and litter-matched WT mice were given a single bolus injection of 2 μg/g anti-GPIbα antibody and platelet counts measured daily pre-/postinjection (n = 3-5 mice/genotype per time point; mean ± SEM; **P < .01, ***P < .001). (F) Serum Tpo concentrations (pg/mL) were measured for Shp1 KO (n = 9), Shp2 KO (n = 8), Shp1/2 DKO (n = 15), and litter-matched control mice (Shp1 WT, n = 9; Shp2 WT, n = 8; and Shp1/2 WT n = 6; *P < .05, **P < .01).