PO-mRNA-LNP transfected platelets respond appropriately to agonists, are coagulable, and have normal morphology. (A) Platelet activation without agonist or after stimulation by ADP, thrombin, CaI, or CRP-XL measured by the MFI (bars, left y-axis) and percentage platelet activation (yellow circles, right y-axis) of surface CD62P. (B) Quantification of MFI (bars, left y-axis) and the percentage of platelets (yellow circles, right y-axis) positive for annexin V. (C) Quantification of MFI (bars, left y-axis) and percentage of platelets (yellow circles, right y-axis) positive for PAC-1. (D) Representative ROTEM curves, with clotting initiated by thromboplastin. (E and F) Quantification of ROTEM clot time (E) and maximum clot firmness (F). The red shaded region is the clinically accepted reference ranges for each parameter.⁴⁰ Platelets were transfected at a supraphysiological concentration of 800 × 10⁶ mL⁻¹. (G) Transmission electron micrographs of platelets without LNP (No LNP), treated with PO-mRNA-LNP, or activated with 5 μg mL⁻¹ CRP-XL. The scale bar indicates 500 nm. Platelets were transfected at a concentration of 250 × 10⁶ mL⁻¹. P values were determined by the 2-way analysis of variance (ANOVA), the 1-way ANOVA, or the unpaired Student t-test (2-tailed). Values are reported as mean ± standard error of the mean. n = 3. Ns, not significant.