Antidotes normalize impaired fibrin formation and fiber diameter of edoxaban-treated clots. Blood clots were generated by incubating antidotes in noncitrated whole blood containing 200 ng/mL edoxaban at 37°C. (A-B) Clots formed in the presence of edoxaban (200 ng/mL, final) have fewer fibers compared with the buffer control. However, normal clot signatures can be observed in edoxaban clots, treated with 50, 100 and 200 µg/mL of Andexanet Alfa or PER977, respectively. Clot images were taken at 2 magnifications (original magnification ×2500 and ×5000, respectively. Only images from the ×5000 magnification are depicted (scale bars, 5 µm). (C) Blood clot fiber diameters in edoxaban (Edox)–treated clots formed in the absence or presence of an antidote. Fiber diameters were measured from scanning electron micrographs using ImageJ software. A total of 60 fibers were analyzed from 2 independent experiments. Fibers for size analysis were selected from 4 images by probing 4 different spots in each image. Data are median with interquartile ranges (n = 60). Black horizontal lines represent median, and error bars represent interquartile range. Statistical significance for fiber diameter was determined by comparing the antidote treated group to the buffer control using a Kruskal-Wallis test followed by a Dunn post-test. Asterisks indicate significant differences in comparison with the buffer control. A significant reduction in fiber diameter was observed in edoxaban-containing clots compared with the buffer control (****P < .0001). The diameter of fibrin fibers formed in edoxaban clots containing 50, 100, and 200 µg/mL Andexanet Alfa is comparable to that of the buffer control. A similar effect was observed with 50 and 100 µg/mL PER977. However, fiber diameters formed in the presence of 200 µg/mL PER977 were significantly larger than the buffer control clot (***P = .0004).