Effects of 14E11 and APC treatment on coagulation and inflammation. Mice treated with 14E11 have less platelet consumption and decreased inflammation after CLP sepsis. (A) Platelet counts were measured in cohorts killed at designated time points after CLP (n = 7 or 8 for each group per time point). Vehicle-treated mice show a progressive drop in platelet count after bowel perforation (36 hours after infection). *P < .05 (vehicle vs sham). (B) All CLP groups show a similar decrease in circulating leukocytes (WBCs) and (C) similar migration of leukocytes into the peritoneal cavity. (D) Microscopic images of representative liver sections from normal, sham-operated, and vehicle-, 14E11-, and APC-treated septic mice (hematoxylin and eosin stain). For histologic evaluation, all animals received vehicle, APC, and 14E11 immediately after CLP (0 hours). Mice were killed 36 hours after CLP, saline perfused, and the organs were fixed in 10% zinc-buffered formalin. Vehicle-treated mice show multifocal thrombosis in the liver, whereas 14E11- and APC-treated mice had a lower density of occluded vessels per field. Histologic sections were visualized with a Nikon Optiphot-2 upright microscope using a 10× objective. Bright-field images were captured with a Hitachi HV-C20 CCD camera and processed using SPOT Basic Version 3.5.0 software. Scale bar represents 150 μm. (E) TAT levels in the plasma are elevated for all groups at 12 hours after surgery, and TAT remains elevated in the vehicle-treated group at 24 hours, suggesting sustained thrombin generation. *P < .05 (vehicle vs sham). (F) TNF-α and (G) IL-6 levels are increased in vehicle-treated mice compared with 14E11-treated animals 12 hours after CLP (n = 7 or 8 for each group per time point), suggesting an anti-inflammatory mechanism for 14E11 during sepsis. *P < .05. Data are mean ± SEM.