FVIII deficiency did not correct the pathologic phenotype of Plg^−/−mice. (A) The estimated weight measurements of a cohort of 25 WT, 58 F8^−/−, 21 Plg^−/−, and 61 F8^−/−/Plg^−/− mice that were followed for up to 168 days. Signs above the x-axis indicate where the weight of Plg^−/− (red squares) and F8^−/−/Plg^−/− (purple diamonds) deviated significantly from that of WT and F8^−/− mice, respectively, and where the weight was significantly different between F8^−/−/Plg^−/− and Plg^−/− mice (open green squares) and between F8^−/− and WT mice (blue circles). The weight data were analyzed with a repeated-measurement ANOVA; P < .05 was considered significant. (B) Frequency of rectal prolapse in 31 WT, 51 F8^−/−, 23 Plg^−/−, and 39 F8^−/−/Plg^−/− mice. (C) Survival analysis from a cohort of 30 WT, 43 F8^−/−, 23 Plg^−/−, and 26 F8^−/−/Plg^−/− mice followed for 168 days. Mice were euthanized when reaching predefined humane end points including wasting disease, rectal prolapse, and penile prolapse. The median survival of F8^−/−/Plg^−/− mice was 12.6 weeks, whereas it was 19.6 for Plg^−/− mice. Development of rectal prolapse and survival rate were compared with the log-rank Mantel-Cox test; P < .05 was considered significant. Colored asterisks indicate intergroup comparisons; **P < .01, ****P < .0001.