Histone H4 induces platelet ballooning and release of procoagulant, proinflammatory microparticles. (A) Representative images of platelets from healthy volunteers and trauma patients. (B–D) Impact of histone H4 exposure on platelets. Platelet ballooning (B), surface expression of histone H4 (C), and annexin V binding (D) after stimulation with histone H4 at the indicated concentrations or vehicle for 5 min under stirring conditions (1,200 rpm). (E–I) Histone-induced microparticle production by platelets. Representative flow cytometry plots of vehicle- and histone-treated platelets (E). Quantity of PMPs released (F), expression of histone H4 on surface of PMPs (G), annexin V binding to PMPs (H), and interaction of PMPs with leukocytes (I). Box plots display median, interquartile range, minimum values, and maximum values from 6 independent experiments. *P < 0.05 **P < 0.01 ***P < 0.001 vs. vehicle, 1-way ANOVA with Dunnett’s posttest.