ABT-737 induces caspase activation and promotes thrombin generation independent of platelet activation. Washed human platelets (3.0 × 10^8/mL) or C57BL/6 (C57) or PAR4-deficient mouse platelets (PAR4^−/−; 0.5 × 10⁸/mL) resuspended in Tyrode buffer in the absence (A,B) or presence (C-F) of BSA were incubated with vehicle (DMSO), CRP (10 μg/mL; 20 minutes), calcium ionophore A23187 (A23187; 1 μM; 20 minutes), or ABT-737 (737; 1 μM; 90-180 minutes). In some experiments, platelets were preincubated with PGE₁ (2 μg/mL) and theophylline (20 mM; PGE₁/Theo), before ABT-737 treatment. (A,B) Human platelets were lysed for Western blot analysis of procaspase-3, gelsolin, and filamin cleavage, as described in “Methods.” Immunoblots are representative of 3 independent experiments. (C-F) The ability of human (C-E) or PAR4^−/− mouse platelets (F) to promote thrombin generation was assessed with the use of a Thrombinoscope (Thromboscope BV), as described in “Methods.” Line graphs (C,E) are taken from 1 representative of 3 independent experiments. Histograms (D,F) represent the means ± SEM (n = 3; ^nsP > .05; **P < .005).