Targeting FXI or FXII limits fibrinogen consumption, coagulopathy, and circulating TF in ECMO. (A) Shown are plasma fibrinogen levels at baseline, 5 minutes after citrate reversal, and at the end of the ECMO run. Note that depletion of FXI or FXII maintained plasma fibrinogen levels compared with heparin treatment. (B) Shown are measurements of plasma TF activity pre- and post-ECMO. (C) Shown are results of TGAs initiated with 5 pM TF in control (purple), FXII-depleted (blue), and FXI-depleted (green) rabbits pre-ECMO, 5 minutes after citrate reversal, and at the end of the ECMO run. ECMO resulted in a significant increase in the lag time and a decrease in peak thrombin in control rabbits, whereas thrombin generation remained relatively stable in the FXII ASO-treated rabbits. As expected, FXI depletion resulted in a decrease in thrombin generation at baseline, but overall thrombin generation remained stable throughout the ECMO run. Note that 1 of the control rabbits had no measurable thrombin generation at the end of the ECMO run. ∗∗P < .01, 2-way analysis of variance; data represent the mean and SEM.