FXII is not crucial for VT that follows inhibition of antithrombin and protein C. (A) Thrombin generation peak heights. Thrombin generation was induced by 20 μg/mL ellagic acid (EA; left graph) or 1 pM TF (right graph) in plasma from WT mice (open circles) or F12-deficient mice (F12^−/−; filled circles). Significance was determined by using the Mann-Whitney rank sum test. (B) Clinical phenotype in WT and F12^−/− mice treated with siRNAs targeting Serpinc1 and Proc. Mice showing characteristic clinical signs (blue bars) and mice unaffected (red bars) 2 days after siRNA treatment (end of experiment). P = 1.00, Fisher’s exact test. (C) Representative coronal head section stained by using the Carstairs’ method of a normal WT mouse (no siRNA treatment). (D-E) Representative coronal head sections of WT and F12^−/− mice stained by using the Carstairs’ method. Both mice developed siSerpinc1/siProc–associated thrombotic coagulopathy. Black bars represent 2000 µm. (F) Descriptive scoring for the type of detected thrombi. 0: no thrombi found; I + II: thrombi categories were based on structure and layering. Blue bars: WT (n = 21); red bars: F12^−/− (n = 22). (G) Levels of fibrin deposition in the liver in the control group (WT; open circles) and the F12^−/− group (F12^−/−; filled circles). P = .001, Mann-Whitney rank sum test. Solid and dashed lines indicate fibrin levels found in a pool of uninjected WT, F12^−/−, and F11^−/− C57BL/6J female mice (median and range, respectively, 5.9 ng/mg [3.8, 10.2], n = 8).