Syk^{R41Afl/fl;PF4-Cre} platelets respond normally to integrin αIIbβ3 outside-in signaling. (A) WT and Syk^{R41Afl/fl;PF4-Cre} (R41A) platelets (2 × 10⁷/mL) were allowed to spread on coverslips coated with fibrinogen (100 μg/mL) for 45 minutes (n = 3). (B) WT and R41A platelets (5 × 10⁸/mL) were allowed to spread in 6-cm wells coated with fibrinogen (100 μg/mL) for 45 minutes in the presence of PRT318 (5 μM) (i), PP2 (20 μM) (ii), or vehicle. Adherent platelets were then lysed, followed by phosphotyrosine (4G10) immunoprecipitation. Precipitated proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot for phosphotyrosine (n = 3). (C) A clot was initiated in WT and R41A PRP with 10 U/mL thrombin and allowed to retract for 60 minutes (n = 3).