NLRP3 and BTK regulate platelet aggregation in sickle cell mice. (A) Platelet caspase-1 activity is increased in homozygous Townes SCD mice compared with heterozygous and control mice. (B) IV injection of MCC950 (50 mg/kg body weight) or ibrutinib (10 mg/kg body weight) suppresses upregulated platelet caspase-1 activity in homozygous SCD mice. (C) Platelet aggregation is elevated in homozygous Townes SCD mice compared with heterozygous and control mice. (D) IV injection of MCC950 or ibrutinib interferes with upregulated platelet aggregation in homozygous SCD mice. Data are shown as mean ± SD of the results from ≥3 separate experiments (n ≥ 3 mice per group). *P < .05, **P < .01, ***P < .001, 1-way ANOVA with Bonferroni post hoc test (A,C), 2-way ANOVA with Bonferroni post hoc test (B,D).