Effect of treatment with saline, or control, HRG, or FXII ASOs on ex vivo catheter-induced thrombin generation. Rabbit plasma was collected after a 4-week course of treatment with saline (n = 6 per group), or HRG or FXII ASOs (n = 8). (A) Plasma was incubated in the absence or presence of catheter segments for 15 minutes at 37°C before clotting was initiated by the addition of 20 mM CaCl₂. Absorbance was monitored, and plasma recalcification clot time was determined as the half-time of maximal absorbance. Thrombin generation was initiated by addition of 20 mM CaCl₂ and was quantified by monitoring the hydrolysis of 1 mM Z-Gly-Gly-Arg-7-amino-4-methyl coumarin (Z-GGR-AMC) thrombin substrate. (B-C) Representative thrombin generation profiles in the absence (B) or presence (C) of catheter segments. (D) Mean lag time and (E) peak thrombin in the absence (red bars) or presence (blue bars) of catheter segments are shown. Bars represent mean ± SD from 3 determinations per rabbit, each performed in duplicate. ^∗P < .05; ^∗∗P < .01; and ^∗∗∗P < .001 comparison of saline-treated plasma in the absence of catheter segments; ^#P < .05 and ^##P < .01 comparison of saline-treated plasma in the absence of catheter segments; ^†P < .05 and ^††P < .01 as indicated by the lines (one-way ANOVA and Holm-Sidak method).