Survival advantage of coagulation factor XI-deficient mice during peritoneal sepsis

Abstract

Anticoagulation is a rational approach to the treatment of sepsis-associated consumptive coagulopathy, but its application is limited because of the risk of excessive bleeding. Factor XI (FXI) contributes substantially to pathological blood coagulation (thrombosis), whereas it contributes only modestly to normal hemostasis. We found that FXI-deficient mice have reduced coagulopathy and increased survival relative to FXI-expressing wild-type mice during cecal ligation and puncture-induced acute peritonitis/sepsis. This finding suggests that FXI contributes to coagulopathy and/or inflammation during sepsis and that pharmacologic inhibition of FXI activity may alter the course and outcome of some infections.

Figure 1. Survival advantage of factor XI (FXI)- deficient mice after large bowel perforation. Kaplan-Meier survival curves (with 95% confidence interval curves) are shown for the survival of 4-7-month-old ageand sex-matched wild-type (WT, or FXI^+/+; n = 47) and FXI^-/- (n = 52) C57Bl/6 mice after cecal ligation and puncture. Curves were compared by the log-rank test, which showed a significant survival advantage for FXI^-/- mice (P = .0001).