Figure 3.

mAb-RC3 inhibits the enhanced platelet aggregation elicited by the Thr120-PAR4 variant. Aggregation of human isolated platelets from donors subsequently genotyped as homozygous at rs773902 for Thr120, Ala120, or as heterozygous. Shown are concentration-response curves to (A) PAR4-AP, (B) thrombin, and (C) thrombin in the presence of the PAR1 inhibitor vorapaxar (90 nM). (D) Also shown are concentration-inhibition curves to mAb-RC3 on responses to thrombin (0.1 U/mL) in the presence of vorapaxar (90 nM), indicating antibody-mediated PAR4 inhibition is equally effective across all genotypes (IC₅₀s for Ala120, Thr120, and heterozygotes = 4.3, 3.1, and 6.8 μg/mL, respectively). (E) An IC₅₀ for mAb-RC3 of 5.1 μg/mL was determined from the pooled data from all individuals shown in panel D. All data are mean ± standard error of the mean from n = 3 to 6 experiments per genotype. *P < .05 (1-way ANOVA with Dunnett’s test for multiple comparisons between each genotype).