Amitriptyline reduces MP generation. (A-B) Human SS RBCs were incubated in PBS with or without amitriptyline for 1 or 24 hours. Flow cytometry plots of MPs and RBCs 1 hour (A) and 24 hours (B) after amitriptyline treatment. (C) Quantification of MP percentage after treatment. (D) Acid SMase activity in mice after amitriptyline injection. (E) Gating strategy for identifying MPs and EMPs in vivo in WT mice. (F) Quantification of MP production in WT mice after normoxic/hypoxic conditioning with or without amitriptyline. *P < .05 compared with vehicle, and P < .05 compared with 1 μM.