Figure 3
Figure 3. ABT-263 induces thrombin generation but inhibits platelet activation and aggregation. (A) Washed human platelets were incubated for 2 hours at 37°C in HBS with ABT-263 (1μM), ABT-737 (1μM), or for 10 minutes with CRP-XL (2 μg/mL), TRAP (100μM), or A23187 (10μM). Thrombin generation over time was measured by calibrated automated thrombography. Data are shown from one representative donor typical of 3 examined. (B) Washed platelets were incubated in HBS with ABT-263 (0, 0.1, or 1μM) for 2 hours before exposure to the platelet agonists CRP-XL, A23187, or TRAP for 10 minutes. Platelet activation was assessed by exposure of P-selectin and flow cytometry. (C-D) Whole blood was incubated with ABT-263 (0, 1, 3, or 10μM) for 2 hours. PRP count was adjusted with autologous filtered PPP to 1.5 × 108/mL and either (C) fibrinogen binding was assessed by flow cytometry or (D) aggregation was measured using an aggregometer. Data are mean ± SD (n = 3, except 3μM ABT-263 in panel D, when n = 2). Statistical significance was tested using analysis of variance and comparison of “no ABT-263” with “ABT-263 (0.1)” and “ABT-263(1)” in panel B and with “ABT-263(1)” and “ABT-263(10)” in panels C and D. *P < .05.

ABT-263 induces thrombin generation but inhibits platelet activation and aggregation. (A) Washed human platelets were incubated for 2 hours at 37°C in HBS with ABT-263 (1μM), ABT-737 (1μM), or for 10 minutes with CRP-XL (2 μg/mL), TRAP (100μM), or A23187 (10μM). Thrombin generation over time was measured by calibrated automated thrombography. Data are shown from one representative donor typical of 3 examined. (B) Washed platelets were incubated in HBS with ABT-263 (0, 0.1, or 1μM) for 2 hours before exposure to the platelet agonists CRP-XL, A23187, or TRAP for 10 minutes. Platelet activation was assessed by exposure of P-selectin and flow cytometry. (C-D) Whole blood was incubated with ABT-263 (0, 1, 3, or 10μM) for 2 hours. PRP count was adjusted with autologous filtered PPP to 1.5 × 108/mL and either (C) fibrinogen binding was assessed by flow cytometry or (D) aggregation was measured using an aggregometer. Data are mean ± SD (n = 3, except 3μM ABT-263 in panel D, when n = 2). Statistical significance was tested using analysis of variance and comparison of “no ABT-263” with “ABT-263 (0.1)” and “ABT-263(1)” in panel B and with “ABT-263(1)” and “ABT-263(10)” in panels C and D. *P < .05.

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