Targeting FXII limits thrombotic complications and prolongs ECMO circuit life (heparin/protamine cohort). (A) Shown is a western blot of plasma FXII in 3 rabbits after 4 weeks of FXII ASO treatment (20 mg/kg) and in control rabbit plasma. Note that the plasma levels of FXII protein in these animals were all below the detection limit of this assay. (B) FXII ASO treatment resulted in a significant decrease in plasma FXII activity (∼5% of controls) but had no effect on FXI activity (C), or fibrinogen levels (D). Note that plasma from FXII ASO-treated rabbits was analyzed before (control) and after ASO treatment (FXII ASO) for factor activities and fibrinogen. Data obtained before treatment were included in the control cohort. (E-H) Shown are the results of experiments where donor rabbit blood was anticoagulated with heparin, followed by protamine reversal. (E) FXII-depletion prolonged the time to circuit failure (P = .07, Kaplan-Meier analysis). (F) Shown are the pressures across the oxygenator as a function of time for each animal. (G) The maximal pressures across the oxygenator were higher in control animals relative to animals with depleted FXII (P = .07, Mann-Whitney U test.) (H) Shown are examples of large clots observed in 2 of the oxygenators used in control animals. In contrast, none of the oxygenators used in FXII ASO-treated rabbits had gross evidence of clots. P values were generated using a Mann-Whitney U test; the data represent the mean and standard error of the mean (SEM). N.S., not significant.