TRIF is critical for the activation of coagulation cascades in endotoxemia. (A-B) IFN-β messenger RNA (mRNA) expression in lungs, spleens (A), and guts (B) from WT mice vs TRIF KO mice as detected by quantitative polymerase chain reaction after LPS challenge for 2 hours. (C) Plasma levels of IFN-β detected by enzyme-linked immunosorbent assay in WT mice vs TRIF KO mice after LPS treatment (0.4 mg/kg of LPS for 7 hours + 10 mg/kg of LPS for 8 hours). (D) Representative SD-IVM images of thrombin (green), platelet adhesion (blue), fibrin (dark red), and albumin (red) within the liver microvasculature in endotoxemic WT and TRIF KO mice (4 mg/kg of LPS for 6 hours). (E-F) Quantitative analysis of thrombin, platelets, and fibrin probe fluorescence intensity and occluded vessels within the liver microcirculation by using ImageJ software. (G-I) WT and TRIF KO mice were injected with 0.4 mg/kg of LPS for 7 hours followed by 10 mg/kg of LPS for 8 hours. (G) Representative images of immunohistochemical staining of fibrin in livers and lungs are shown (×400). (H) Plasma levels of TAT complexes, PAI-1, fibrinogen (Fib), and D-dimer were measured. (I) Platelet counts were detected. (J) Kaplan-Meier survival plots for WT mice vs TRIF KO mice (n = 11 mice per group). Data are shown as mean ± standard error of the mean. *P < .05; **P < .01; ***P < .001. N = 4 to 11 mice per group. Scale bar, 50 μm.